Cardionerds: A Cardiology Podcast

CardioNerds (Amit Goyal & Daniel Ambinder) join University of California San Diego (UCSD) cardiology fellows (Harpreet Bhatia, Dan Mangels, and Quan Bui) for a relaxing beach bonfire in the beautiful city of San Diego! They discuss a challenging case of post-transplant cardiac allograft vasculopathy. Dr. Hao (Howie) Tran provides the E-CPR and program director Dr. Daniel Blanchard provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Richard Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his late 20s with a past medical history of orthotopic heart transplant, presents with one-week of progressive lower extremity edema and dyspnea with NYHA class IV symptoms. 5 years prior, he underwent orthotopic heart transplant for arrhythmogenic right ventricular cardiomyopathy. Subsequently, he has had multiple episodes of rejection or recurrent graft dysfunction. On presentation, he was normotensive and borderline tachycardic. Exam revealed elevated JVP, decreased breath sounds, and pitting edema.  Labs demonstrated leukocytosis, acute kidney injury, and elevated pro-BNP. TTE demonstrated LVEF 35%, apical akinesis, and grade III diastolic dysfunction (all similar to prior). He was initially diuresed and RHC/EMB was performed to evaluate for rejection. Early in his course, the patient unfortunately suffered a PEA arrest with ROSC was quickly achieved after 1 minute of CPR. He was intubated and cannulated for VA ECMO. EMB demonstrated ISHLT Grade 1R cellular rejection and he was ultimately listed for re-transplant. Shortly thereafter, the patient received an OHT. His pathology demonstrated intimal thickening of all his coronaries, consistent with coronary artery vasculopathy, felt to be the major contributor to his presentation.   Case Media ECG Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. What is CAV?   CAV stands for cardiac allograft vasculopathy. Within the transplanted heart, CAV is the proliferation of vascular smooth muscle and intimal thickening in the epicardial coronary arteries and microvasculature leading to diffuse narrowing. CAV is common, present in greater than 30% of patients at 5 years post-transplant. It is a significant contributor to post-transplant mortality after the first year.   CAV, in contrast to typical atherosclerotic lesions, is diffuse and concentric while atherosclerosis tends to be focal with eccentric luminal narrowing and heterogenous plaque composition. Patients s/p OHT can still develop typical coronary artery disease, likely developed from pre-existing disease in the donor heart. CAV should be high on the differential for the cause of graft dysfunction, especially after the first year post-transplant.   2. How and Why Does CAV Occur?  CAV has multiple contributing factors. There are immunologic and non-immunologic factors, but it appears the immunologic components play the larger role given that the pan-vasculopathy develops in the donor heart and not in the recipient’s vasculature. In CAV, there is chronic immune-mediated injury creating a persistent inflammatory state in the donor coronary endothelium leading to a neointimal proliferative process in the coronaries. Amongst immunologic factors, it appears the number of episodes of cellular rejection correlates with the development of CAV.   CAV occurs when foreign antigens are recognized by the host immune system as “non-self,” a process termed allorecognition.  T-cells are subsequently activated, and release a number of inflammatory cytokines that leads to additional T-cell stimulation, inflammatory cell proliferation, and endothelial cell propagation.  Ultimately this inflammatory cascade leads to smooth muscle cell advancement and intimal growth into the arterial lumen.   Other immunologic factors include HLA mismatch and antibody-mediated rejection. There are numerous non-immunologic factors, including older donor age, CMV infection, hyperlipidemia, insulin resistance, donor brain death secondary to intracranial hemorrhage, and prolonged ischemic time.   3. How Do Patients with CAV Present?   Donor hearts are denervated at explantation, and so post-transplant patients typically will not develop classic anginal symptoms as seen with typical atherosclerotic coronary disease. Thus, routine surveillance is necessary (see below).   If not diagnosed early, the clinical presentation may include LV dysfunction (with or without symptoms), acute myocardial infarction, heart block, arrhythmias, syncope, or sudden cardiac death.   4.  How Do We Diagnose CAV?  Routine surveillance is necessary because patients are generally asymptomatic and there is a high incidence of CAV posttransplant.   The most common method for screening includes coronary angiography, but its sensitivity is reduced compared to traditional atherosclerotic disease as CAV is diffuse. Intravascular ultrasound (IVUS) significantly improves sensitivity and the early the detection of disease.   The timing and method of screening will be center-specific. As the patient is farther removed from their transplant date, dobutamine stress echo may be a reasonable method to screen for CAV. Myocardial perfusion imaging, specifically with PET Rest/Stress with absolute myocardial blood flow quantification, and coronary CTA may also be effective methods to diagnose CAV.   The ISHLT grading of CAV by angiography is as follows:  CAV0 (Nonsignificant): No detectable angiographic lesion  CAV1 (mild): Angiographic LM lesion <50%; or primary vessel with maximum lesion of <70%; or any branch vessel stenosis <70% without allograft dysfunction  CAV2 (moderate): Angiographic LM <50%; or a single primary vessel ≥70% stenosis; or isolated branch stenosis in 2 systems ≥ 70% without allograft dysfunction  CAV3 (Severe): Angiographic LM ≥50%; or ≥2 primary vessel ≥70% stenosis; or isolated branch stenosis in all 3 systems ≥70%; CAV1 or CAV2 with allograft dysfunction or evidence of significant restrictive physiology  5. How Do we Treat CAV?   Primary prevention remains key. Statins have been shown prospectively to reduce cardiac allograft vasculopathy and improve survival. Chronic immunosuppression is the foundation of post-transplant care. The mTOR inhibitors, everolimus and sirolimus, harbor antiproliferative properties that may prevent allograft vasculopathy. However, these are generally not first-line immunosuppressive medications in the United States, given the potential for multiple side effects including impaired wound healing in new transplant patients. In patients with documented or progressive CAV, escalation of immunosuppression to sirolimus may be considered. Revascularization for patients may be considered, given the morbidity associated with CAV, though no survival advantage has been shown. In patients with severe CAV, re-transplantation should be considered.   References Mehra, M. R., Crespo-Leiro, M. G., Dipchand, A., et. al (2010). International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy—2010.  Chih, S., Chong, A. Y., Mielniczuk, L. M. et. al. (2016). Allograft vasculopathy: the Achilles’ heel of heart transplantation. Journal of the American College of Cardiology, 68(1), 80-91.  Schmauss, D., & Weis, M. (2008). Cardiac allograft vasculopathy: recent developments. Circulation, 117(16), 2131-2141.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Virginia Commonwealth University (VCU) cardiology fellows (Ajay Pillai, Amar Doshi, and Anna Tomdio) for a delicious skillet breakfast and amazing day in Richmond, VA! They discuss a fascinating case of a patient with Wolff-Parkinson-White (WPW) and hypertrophic cardiomyopathy (HCM). Dr. Keyur Shah provides the E-CPR and program director Dr. Gautham Kalahasty provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai. Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his mid-60s presented to the ED after an episode of unwitnessed syncope while drinking. Patient had suddenly passed out from a seated position with no prodrome or post-ictal state. He had episodes like this in the past, which were thought to be seizures, but otherwise PMHx only notable for alcohol use disorder. He denied any FH of SCD or syncope. In the ED, exam was unremarkable. Labs notable for mild thrombocytopenia, mild hyponatremia with AKI, 2:1 AST/ALT ratio, elevated NT-proBNP, and a very high lactate that rapidly corrected with fluids. EKG was notable for sinus tachycardia, short PR interval, wide QRS, and delta waves consistent with Wolff-Parkinson-White (WPW) pattern. Echo showed preserved LVEF, thickened LV septum (1.6 cm) and posterior wall (1.3 cm) concerning for hypertrophic cardiomyopathy (HCM). No outflow tract gradient was noted at rest or with stress, and the strain pattern demonstrated apical sparing. Evaluation for cardiac amyloid, including plasma cell dyscrasia and PYP scan, was negative. Cardiac MRI confirmed severely thickened LV inferior and inferolateral walls at 1.7 cm with no LVOT obstruction. 25% of the myocardium demonstrated patchy LGE.   Due to concern for WPW syndrome, the patient underwent an EP study. This revealed a malignant septal accessory pathway that was successfully ablated with resolution of the WPW EKG features. Given large LGE burden in setting of HCM, patient underwent placement of primary prevention ICD. Genetic testing for PRKAG2 mutation is pending given comorbid WPW and HCM.  Case Media A E C D B F Click to Enlarge A. CXR: Slightly increased interstitial markings in the lung bases, an elevated right hemidiaphragm. No acute airspace disease or pulmonary edemaB. ECG: Sinus tachycardia rate 120bpm, PR interval 80ms, QRS 130ms, WPW pattern.  Arruda algorithm localizes to posterior septum.C. CMR:  Myocardium nulls before blood pool.D. CMR:  Delayed gadolinium enhancementE. Follow up ECG: NSR 78, repolarization abnormalities.  T wave memory inferior leads.F. CXR status post dual chamber ICD implantation TTE: Apical 4 chamber TTE: Apical 2 chamber TTE: Apical 3 chamber TTE: Strain imaging CMR: 4 chamber cine CMR: 2 chamber cine CMR: 3 chamber cine CMR: Short axis cine at base level CMR: Short axis cine at mid-papillary level CMR: Short axis cine at apical level Episode Schematics & Teaching Hypertrophic Cardiomyopathy Infographic Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case Our patient was found to have Wolff-Parkinson-White (WPW) pattern. What are the diagnostic criteria for WPW pattern and how does it differ from WPW syndrome? How can you localize the accessory pathway using the EKG?  WPW pattern refers to the presence of the below criteria on a patient’s surface EKG in the absence of symptomatic arrhythmias. If symptomatic arrhythmias related to the accessory pathway occur, then it is WPW syndrome. Symptoms may include palpitations, shortness of breath, presyncope, syncope, and sudden cardiac death (SCD).   Not all patients with accessory pathways have EKG findings as only 60-75% of accessory pathways are “manifest” (meaning they conduct antegrade from atria to ventricles or are bidirectional). Conversely, a “concealed” accessory pathway only conducts retrograde (from ventricles to atria) and would not be apparent on resting sinus EKG; these patients can have WPW diagnosed after a ventricular premature beat, ventricular pacing, or an EP study that shows retrograde conduction through the accessory pathway.   The WPW pattern is diagnosed by the following EKG criteria:  Short PR interval < 120 ms  Signs of pre-excitation: a delta wave (slurred upstroke of QRS complex) and QRS > 120 ms. The degree of pre-excitation on EKG depends on the position (how much of the ventricular myocardium is depolarized by the accessory pathway) and depolarization speed of the accessory pathway (more rapid conduction leading to earlier ventricular depolarization and wider delta wave).   We can use EKG findings to localize accessory pathways using the Arruda Criteria, which has an overall sensitivity of 90% and specificity of 99%. Note, patients who have a left-lateral bypass tract as the antegrade limb may not have delta waves on surface EKG, as the atrial impulse can take longer to reach the bypass tract than the AV node.    What are the major mechanisms for WPW and how do they lead to early activation of the ventricles? How can this precipitate arrhythmias?  Accessory pathways are abnormal congenital connections between the atria and ventricles when there is incomplete atrio-ventricular isolation during fetal development. They can be associated with congenital cardiac malformations like Ebstein anomaly.  Depolarization of the ventricles occurs via the AV node and the accessory pathway simultaneously, leading to early depolarization of a portion of the ventricles and the characteristic delta wave. Depolarization through the His Purkinje system reaches the apex first and travels back up the ventricle, meeting the slower cell to cell conduction from the accessory pathway and causing termination of the impulses. The resulting QRS complex is essentially a “fusion beat” between the two sources.  Accessory pathways often have more rapid conduction, but longer refractory periods than the AV node. If a PAC occurs when the accessory pathway is refractory, there will be antegrade conduction solely through the AV node. As the impulse travels through the ventricles it can conduct retrograde through the accessory pathway from V to A. This creates a reentrant pathway that results in atrioventricular reentrant tachycardia (AVRT), which accounts for up to 80% of SVT in WPW. Orthodromic AVRT (antegrade through AV node, retrograde through accessory pathway) accounts for 90-95% of AVRT in WPW.   Other tachycardias can occur where the accessory pathway is a bystander and not required for initiation and maintenance of the arrhythmia like in AVRT. This includes atrial arrhythmias (e.g., atrial fibrillation, atrial flutter), ventricular tachycardia, and ventricular fibrillation. Atrial fibrillation is relatively common (~20%) in WPW syndrome patients. Atrial fibrillation with an accessory pathway can produce rapid ventricular rates due to unencumbered conduction via the accessory pathway. In these situations, QRS width and morphology may vary due to variable conduction via the AV node vs accessory pathway. Depending on the rate of conduction, the patient can degenerate into VF. A shorter refractory period places patients at the highest risk for VF.   How do we risk stratify patients with WPW pattern? When would an EP study (EPS) be beneficial? What features are high risk on EPS and would warrant treatment?  Patients who are asymptomatic are typically at low risk of sudden cardiac death. Those who do have SCD typically have symptoms at some point prior to arrest. Patients with intermittent loss of the delta wave on a beat-to-beat basis are likely at lower risk, as it suggests the accessory pathway lacks the ability for rapid AV conduction. However, persistent delta wave in asymptomatic patients may still be at low risk.   The risk for SCD is thought to be due to rapid conduction of Afib down the accessory pathway leading to VF. Accessory pathways with shorter refractory periods are able to conduct at higher rates (shorter R to R intervals). Delta waves disappear when R to R interval is less than the refractory period, at which point the atrial impulse only conducts through AV node. Thus, the lower the HR that delta waves become intermittent, the lower the risk of SCD.  We can start risk stratification in most patients noninvasively with a resting EKG and exercise EKG stress test, unless we clearly demonstrate intermittent delta wave at rest. If preexcitation persists even with maximal sinus heart rates, then an EPS is recommended.   High risk features on EPS include multiple accessory pathways, inducible AVRT or Afib, shortest pre-excited RR interval (SPERRI) < 250 ms, and accessory pathway refractory period < 240 ms  How are high risk WPW pattern and WPW syndrome treated?  For the chronic prevention of arrhythmia:  In patients with high risk WPW pattern, we typically refer for catheter ablation (typically radiofrequency ablation though cryoablation can be utilized) of the accessory pathway to help prevent SCD. Successful ablation is curative.   In patients with WPW syndrome, we can still risk stratify with the above algorithm, but symptomatic patients should receive treatment. Ablation is first line for all patients who are candidates and willing given success rates of 90-95%.  In terms of medical therapy for patients who are not ablation candidates, flecainide and propafenone are reasonable options in the absence of structural heart disease. Dofetilide or sotalol are options in patients with structural heart disease. AV nodal blocking agents can be considered in the setting of orthodromic AVRT.  For WPW patients presenting with an acute arrhythmia and who are hemodynamically unstable, synchronized cardioversion is first line therapy. Pharmacologic therapy in the hemodynamically stable patient depends on the suspected level of involvement of the accessory pathway and type of arrhythmia. For arrhythmias not dependent on the accessory pathway for initiation and maintenance (e.g., atrial fibrillation), AV nodal blocking agents can induce rapid antegrade conduction down the accessory pathway which could degenerate into ventricular fibrillation. In the setting of rapid pre-excited atrial fibrillation, procainamide or ibutilide are the agents of choice.   AVRT requires the accessory pathway for initiation and maintenance of the arrhythmia. Orthodromic AVRT will typically be a narrow complex tachycardia (unless there is aberrancy) and can be managed similarly to other regular narrow complex tachycardias (e.g., use of adenosine). If there is any doubt about the diagnosis, procainamide should be utilized.    Where do the diagnostic schema for WPW and HCM overlap and what syndrome should you think of in patients where they coexist?  Familial WPW is rare and characterized by the autosomal dominant inheritance of the combination of WPW syndrome and non-sarcomeric HCM. It is caused by mutations in the PRKAG2 gene, which encodes a portion of 5’AMP-activated protein kinase (AMPK). This mutation leads to cardiac glycogen overload, resulting in ventricular hypertrophy (HCM phenocopy), WPW-like syndrome, AV block, and progressive conduction system disease.   Cardiac myocyte glycogen accumulation is thought to decrease the myocardial activation threshold and so overcomes the insulating properties of the AV annulus fibrosus, resulting in electrical leak between the atria and ventricles. This gives the clinical appearance of an accessory pathway. Given the typical absence of a distinct accessory pathway, EPS with ablation is often not effective.   Other glycogen storage disorders may cause a similar overlap between an HCM phenocopy and WPW mimic like Pompe disease and Danon disease.  References Aggarwal, V., Dobrolet, N., Fishberger, S., Zablah, J., Jayakar, P., & Ammous, Z. (2015). PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis. Annals of Pediatric Cardiology, 8(2), 153.  Arruda, M. S., McCLELLAND, J. H., Wang, X., Beckman, K. J., Widman, L. E., Gonzalez, M. D., Nakagawa, H., Lazzara, R., & Jackman, W. M. (1998). Development and Validation of an ECG Algorithm for Identifying Accessory Pathway Ablation Site in Wolff-Parkinson-White Syndrome. Journal of Cardiovascular Electrophysiology, 9(1), 2–12.  Calkins Hugh, Yong Patrick, Miller John M., Olshansky Brian, Carlson Mark, Saul J. Philip, Huang Shoei K. Stephen, Liem L. Bing, Klein Lawrence S., Moser Suzan A., Bloch Daniel A., Gillette Paul, & Prystowsky Eric. (1999). Catheter Ablation of Accessory Pathways, Atrioventricular Nodal Reentrant Tachycardia, and the Atrioventricular Junction. Circulation, 99(2), 262–270.  Chhabra, L., Goyal, A., & Benham, M. D. (2020). Wolff Parkinson White Syndrome (WPW). In StatPearls. StatPearls Publishing.  Gollob, M. H., Green, M. S., Tang, A. S.-L., Gollob, T., Karibe, A., Hassan, A.-S., Ahmad, F., Lozado, R., Shah, G., Fananapazir, L., Bachinski, L. L., Tapscott, T., Gonzales, O., Begley, D., Mohiddin, S., & Roberts, R. (2001). Identification of a Gene Responsible for Familial Wolff–Parkinson–White Syndrome. New England Journal of Medicine, 344(24), 1823–1831.  Gollob Michael H., Seger John J., Gollob Tanya N., Tapscott Terry, Gonzales Oscar, Bachinski Linda, & Roberts Robert. (2001). Novel PRKAG2 Mutation Responsible for the Genetic Syndrome of Ventricular Preexcitation and Conduction System Disease With Childhood Onset and Absence of Cardiac Hypertrophy. Circulation, 104(25), 3030–3033.  Miyamoto, L. (2018). Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome. The Journal of Medical Investigation: JMI, 65(1.2), 1–8.  Page, R. L., Joglar, J. A., Caldwell, M. A., Calkins, H., Conti, J. B., Deal, B. J., Estes III, N. A. M., Field, M. E., Goldberger, Z. D., Hammill, S. C., Indik, J. H., Lindsay, B. D., Olshansky, B., Russo, A. M., Shen, W.-K., Tracy, C. M., & Al-Khatib, S. M. (2016). 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia. Heart Rhythm, 13(4), e136–e221.  Spector, P., Reynolds, M. R., Calkins, H., Sondhi, M., Xu, Y., Martin, A., Williams, C. J., & Sledge, I. (2009). Meta-Analysis of Ablation of Atrial Flutter and Supraventricular Tachycardia†. American Journal of Cardiology, 104(5), 671–677. Talle, M. A., Buba, F., Bonny, A., & Baba, M. M. (2019). Hypertrophic Cardiomyopathy and Wolff-Parkinson-White Syndrome in a Young African Soldier with Recurrent Syncope. Case Reports in Cardiology, 2019.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Baylor College of Medicine cardiology fellows (Khurrum Khan, John Suffredini, and Aliza Hussain) during restaurant week in Houston! They discuss an interesting case of STEMI in a patient with a recent diagnosis of e-cigarette or vaping product use-associated lung injury (EVALI). Dr. Vijay Nambi provides the E-CPR and APD Dr. Arunima Misra provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Bibin Varghese with mentorship from University of Maryland cardiology fellow Karan Desai.    Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A male in his mid 40s with a 30 pack year smoking history, EVALI (e-cigarette and vaping associated lung injury), and asthma presented with dyspnea and persistent chest pain. He had been vaping for the past year. One month prior , CT chest showed bilateral patchy infiltrates and he was diagnosed with EVALI and started on a steroid taper with resolution of his CT abnormalities. A nuclear stress test at that time was negative for ischemia. On arrival, he was in sinus tachycardia, normotensive, and not on oxygen supplementation. Physical exam was negative for volume overload or heart murmurs. EKG showed new Q waves with STE in V2-V4, with associated Q waves and TWI in the lateral leads and troponin returned moderately elevated. He was emergently taken to the cath lab which showed an abrupt cutoff of flow to the LAD. He received a single DES with resolution of coronary flow. A post-cath TTE showed an LVEF of 40-45% with apical anterior and anteroseptal WMA. He was monitored in the CCU the next day and he was treated with aspirin, ticagrelor, ACEi, metoprolol succinate and high intensity statin and subsequently discharged in stable condition with cardiac rehab follow-up. Case Media A B Click to Enlarge A. Presentation ECG (Anterior STEMI) B. Baseline ECG LAD occlusion Post PCI RCA TTE 1 TTE 2 TTE 3 Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. The patient presented with a STEMI following a diagnosis of EVALI. What is known about the cardiovascular risks of vaping and e-cigarette use?  The overall cardiovascular risks of e-cigarette use remains to be elucidated  In preclinical studies, e-cigarettes use have been linked to increased sympathetic activity, oxidative stress, endothelial dysfunction, vascular injury, and altered platelet activity  One observational study has suggested that daily e-cigarette users were 1.79 times more likely to experience MI than individuals who had never used e-cigarettes.  Additional high-quality randomized controlled trials are needed to conclusively establish the safety and efficacy of e-cigarettes.  2. So the data is still emerging regarding the overall cardiovascular risks of e-cigarette use. Of note, the patient had a negative stress test a month prior. Should that not translate into low likelihood of cardiovascular events?  Remember that stress testing for the diagnosis of obstructive coronary disease is most helpful in patients with an intermediate pretest probability for coronary artery disease. Further myocardial ischemia can occur not only secondary to obstructive epicardial disease (which may be new and acute from plaque rupture/erosion), but also from microvascular disease, vasospastic disease, and so forth. Stress testing with radionuclide myocardial perfusion imaging (e.g., SPECT, PET) is a well-established method for assessing coronary disease, but it is not an anatomic assessment. With nuclear stress tests, the causes of a false-negative result could include submaximal exercise (if doing exercise stress), collateral or overlapping epicardial circulation, suboptimal images (including artifact and poorly timed stress images), inaccurate interpretation, and balanced ischemia.   Nonetheless, sensitivity for obstructive CAD in SPECT approaches 85-90% with specificity around 70-75%. As SPECT imaging is not an anatomic assessment, a recent negative nuclear stress test does not necessarily mean very low risk for future major adverse cardiovascular events. Even with a normal nuclear stress test, there is a 0.65% – 1.78% annual event rate of death or non-fatal MI.   3. Can non-obstructive and potentially “vulnerable” plaque be detected before an event?  Remember ECG, echocardiographic and radionuclide stress testing are different modalities to assess for obstructive CAD after inducing ischemia via exercise or medications. These modalities typically assess for flow-limiting lesions (e.g., typically greater than 50%). However, acute coronary syndrome can occur subsequently from lesions that were not initially obstructive.   In the PROSPECT study looking at patients who presented with ACS and underwent PCI to the culprit lesion and were followed afterward for ~ 3 years for adverse events, recurrent major adverse plaque rupture events were noted equally at the culprit lesion and at non-culprit lesions. Non-culprit lesions that were responsible for unanticipated events were angiographically mild on initial evaluation, had thin-cap fibroatheromas, or had large plaque burden as determined by gray-scale and radiofrequency intravascular ultrasound.  This is where coronary CTA has an increasingly larger role. A study looking at coronary CTA determined that plaques with positive remodeling and low attenuation features were at higher risk of ACS developing over time. Those individuals with neither of those features had high NPV in ruling out future ACS events. Typically, as a lesion increases in size, it can compromise luminal blood flow when 50% or greater narrowing of the lumen is observed (remember this is slightly different than labeling a lesion as “obstructive” to the point of potentially necessitating intervention). However, when there is an absence of luminal loss regardless of lesion size in early lesions, this is called “positive coronary artery remodeling” and there is compensatory enlargement of the epicardial vessel. Post-mortem studies have found that vessels with positive remodeling have been associated with increased lipid content, as well as features associated with unstable plaque (e.g., thin-cap fibroatheroma).   4.  The patient had an MI at age 45! Apart from e-cigarette use, what other evaluation is warranted in a young patient with ACS or STEMI?  Traditional risk factors such as dyslipidemia, T2DM, HTN, and family history of premature CAD must be evaluated as plaque rupture events are still the most common cause of MI in young patients (age < 45 years). Furthermore, the differential for young individuals presenting with acute myocardial infarction should include non-atherosclerotic causes such as: anomalous coronary artery, spontaneous coronary artery dissection, coronary embolus, coronary vasculitis, coronary aneurysm (all of which have been discussed in the @cardionerds #CNCR episodes!).   If thrombus is present on angiography without traditional risk factors, workup should include evaluation for hypercoagulable states (e.g., Protein C and S deficiency, Factor V Leiden, APLS) or evaluating for a source of embolism (e.g., Afib, valvular lesion, LV thrombus, or even PFO [Enjoy Ep #51 – ACS & PFO]). Coronary thrombus may arise in situ from plaque rupture/erosion or as an embolus; recall that coronary emboli may be categorized as: direct, paradoxical, or iatrogenic.  Angiographic and multi-modal imaging findings may reveal the underlying etiology, including SCAD (Enjoy Ep #65 – SCAD), or one of the other non-atherosclerotic coronary processes listed above. If no obvious lesion is present, one should evaluate for Myocardial Infarction with non-obstructive coronaries (MINOCA) such as coronary vasospasm, and coronary microvascular dysfunction  Other considerations in young patients should include drug use, such as cocaine and methamphetamine use. Furthermore, oral contraceptives combined with another pro-thrombotic risk factor (e.g., tobacco use) may lead to acute myocardial infarction.   5.  Sounds like the patient improved symptomatically after PCI placement. Going back to the basics, why do we obtain a TTE after STEMI and monitor in the CCU?    Assessment of resting LV function helps us risk stratify patients, as it is one of the strongest predictors of survival. Furthermore, it will help us guide our medical therapy after STEMI. Echocardiographic evaluation can also help us characterize any suspected mechanical complications of STEMI. Beyond just survival, residual LV systolic function is one of the strongest predictors of sudden cardiac death risk after STEMI. Patients with an initially reduced LV function (e.g., <40%), who do not warrant ICD therapy before discharge, should undergo re-assessment of LV function >40 days after the index event to assess eligibility for ICD therapy. The delay to ICD therapy in this circumstance comes from the results of the DINAMIT trial in which ICD therapy 6 to 40 days after MI in patients with LVEF  ≤ 35% was not shown to reduce overall cardiac death risk.   The cardiac intensive care unit was initially established as a separate ward for the early detection and treatment of arrhythmias following acute myocardial infarction. Monitoring for arrhythmia in the CCU remains a cornerstone of post-STEMI management, as well as mechanical, embolic and inflammatory complications.   Mechanical complications after a STEMI include LV failure and cardiogenic shock, acute severe mitral regurgitation from papillary muscle rupture, ventricular septal rupture, LV free wall rupture, ventricular pseudoaneurysm, and ventricular aneurysm.   LV mural thrombus can cause an embolic complication, especially after a large anterior wall MI and delayed reperfusion.   Inflammatory complications include early and late pericarditis (i.e. Dressler’s syndrome – though this is rarely seen).  References Buchanan, N. D. et al. Cardiovascular risk of electronic cigarettes: a review of preclinical and clinical studies. Cardiovasc. Res. 116, 40–50 (2020).  Hachamovitch, R. et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation 97, 535–543 (1998).  Arbab-Zadeh, A. Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm. Heart Int. 7, (2012).  Falk Erling, Shah Prediman K. & Fuster Valentin. Coronary Plaque Disruption. Circulation 92, 657–671 (1995).  Motoyama, S. et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J. Am. Coll. Cardiol. 54, 49–57 (2009).  Stone, G. W. et al. A Prospective Natural-History Study of Coronary Atherosclerosis. N. Engl. J. Med. 364, 226–235 (2011).  Gulati, R. et al. Acute Myocardial Infarction in Young Individuals. Mayo Clin. Proc. 95, 136–156 (2020).  O’Gara, P. T. et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. J. Am. Coll. Cardiol. 61, e78–e140 (2013).  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Pittsburgh Medical Center cardiology fellows (Agnes Koczo, Natalie Stokes, and Kayle Shapero) for a boat cruise down the Allegheny river as we tour all over beautiful Pittsburgh! They discuss an important case of severe pre-eclampsia, and explore some of the exciting dimensions of cardio-obstetrics. Dr. Malamo Eleni Countouris provides the E-CPR and program director Dr. Katie Berlacher provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Tommy Das with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A G12P7 woman in her mid 30s in the third trimester of pregnancy presented with two months of progressive shortness of breath, orthopnea, and abdominal distension. She has a history of chronic HTN, untreated OSA, and obesity. Evaluation revealed a BP of 147/76 and spot urine protein:creatinine ratio elevated to 0.6, which in the context of her presentation was concerning for preeclampsia superimposed on chronic hypertension. TTE showed preserved ejection fraction, flattened interventricular septum during systole consistent with RV pressure overload, and moderate pulmonary HTN.  She was diuresed with IV furosemide with improvement in symptoms and kept on ASA 81mg. The etiology of her elevated PA pressures was thought to be multifactorial, including untreated OSA for which she was started on CPAP. She was ultimately discharged on oral diuretics, and underwent an uncomplicated spontaneous vaginal delivery at 37 weeks. After delivery, follow-up in a clinic specializing in improving cardiovascular health in women with history of hypertensive disorders of pregnancy was arranged.   Case Media A B C Click to Enlarge A. ECG: Sinus tachycardia otherwise unremarkableB. CXR: Within limitations of respiratory motion, no focal airspace consolidation; no pleural effusionsC. TTE: EF 55-60%, flattened IVS c/w RV pressure overload; normal RV size and function; mod TR; moderate pulmonary HTN (PASP 52mmHG); normal diastolic function Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. Cardionerds, we all should be familiar with #CardioObstetrics. What are the hypertensive disorders of pregnancy?  There are four major categories for hypertensive disorders in pregnancy: (1) chronic hypertension (2) gestational hypertension; (3) preeclampsia (along with eclampsia and HELLP syndrome); (4) chronic hypertension with superimposed preeclampsia.   Chronic Hypertension: Note, the definition of chronic hypertension was updated in the 2017 ACC/AHA guidelines as SBP ≥ 130 or DBP ≥ 90, but the diagnostic criteria for gestational hypertension, pre-eclampsia and chronic hypertension with super-imposed pre-eclampsia have not changed at this time.   Gestational Hypertension (per ACOG guidelines): defined as SBP ≥  140 mmHg or DBP ≥  90 mmHg at least 4 hours apart diagnosed after 20 weeks of gestation without proteinuria or severe features of pre-eclampsia (e.g., renal insufficiency, elevated liver enzymes, thrombocytopenia, hemolysis, pulmonary edema, or CNS symptoms)  Preeclampsia: diagnosis requires  (1) SBP ≥ 140 mmHg or DBP ≥  90 mmHg at least 4 hours apart after 20 weeks gestation or SBP ≥ 160 mmHg or DBP ≥ 110 mmHg once and (2) end organ damage. This includes proteinuria (≥ 300 mg/24hr urine collection, protein/creatinine ratio of ≥ 3 mg/dL, or dipstick reading of 2+ protein if other methods are not available), thrombocytopenia (<100k), renal insufficiency (doubling of serum Cr in the absence of other renal disease or serum Cr > 1.1 mg/dL), elevated liver enzymes (at least 2x upper limit of normal), pulmonary edema, or neurological symptoms (e.g., new onset headache not responding to medications or visual disturbances not attributable to another diagnosis).   Eclampsia: diagnosed when new-onset, grand mal seizure occurs in patients with pre-eclampsia.  HELLP Syndrome: diagnosed when Hemolysis, Elevated Liver enzymes, and Low Platelets are the predominant features. HELLP is likely a subset of preeclampsia. Note, not all patients will have hypertension.   Chronic hypertension with superimposed preeclampsia: (1) characterized by sudden increase in blood pressure that was previously controlled or recent up-titration of antihypertensives to manage blood pressure and/or (2) new onset proteinuria or increase in pre-existing proteinuria  2. This case featured a patient with super-imposed pre-eclampsia; what is pathophysiology behind this disorder?  The pathophysiology of preeclampsia is complex and includes multi-organ manifestations. The initial insult is thought to be secondary to abnormal trophoblast (the outer cell layer of the blastocyst which eventually gives rise to the embryo) invasion of the endometrium. Normally, as trophoblasts implant in the endometrium, the small myometrial spiral arteries remodel with loss of smooth muscle and elastic lamina from the vessel wall. This allows increased blood flow to the placenta.   In preeclampsia, there is incomplete spiral artery remodeling which can lead to placental ischemia. The incomplete arterial transformation is thought to be mediated by a number of factors, including soluble fms-like tyrosine kinase-1 (sFlt-1). sFlt-1, which circulates in the maternal bloodstream, has been implicated as an underlying culprit to the multi-system endothelial dysfunction we see in pre-eclampsia (e.g., CNS, renal dysfunction). There are other factors involved as well that ultimately lead to widespread oxidative stress, abnormal vascular reactivity, microemboli, and the clinical features of preeclampsia.   There are additionally immunologic and genetic factors that lead to a preeclampsia phenotype by leading to a pro-inflammatory state and reduced trophoblast invasion.   3. Clearly, pre-eclampsia can have severe adverse effects on mother and child. Which patients are at increased risk of pre-eclampsia, and what can be done to lower their risk?  High risk factors for developing preeclampsia include: diabetes, chronic hypertension, chronic kidney disease, multifetal gestation, autoimmune disorders (particularly systemic lupus erythematosus and antiphospholipid syndrome), and previous pregnancy with preeclampsia. Other risk factor include obesity, maternal age over 35 years, and nulliparity.  There is no consensus guideline on what defines moderate to high risk. Following the USPSTF recommendations, any pregnant woman with a high risk factor or several moderate risk factors should be advised to start low-dose aspirin after 12 weeks of gestation to reduce the risk of preeclampsia. A recent Cochrane review that included trial data from nearly 37,000 women found aspirin prophylaxis reduced risk of preeclampsia by 18%.   Calcium supplementation may be of benefit to prevent preeclampsia in women with low-baseline calcium intake. The proposed mechanism is that hypocalcemia may stimulate PTH or renin release, increasing intracellular calcium including in vascular smooth muscle. This may result in vasoconstriction and higher blood pressure and calcium supplementation may attenuate this process.   There is an ongoing clinical trial to investigate the role of Pravastatin in the prevention of preeclampsia.   4. What if my patient has chronic HTN or gestational HTN? How do I approach the hypertensive pregnant patient?  An ounce of prevention is worth a pound of cure! In hypertensive women who may become pregnant, nifedipine, labetalol, hydralazine, or methyldopa are preferred over teratogens like ACE inhibitors, ARBs, or direct renin inhibitors.   Severe HTN (SBP ≥160, DBP ≥110) should always be treated to avoid pulmonary edema, stroke or placental abruption. A more conservative approach can be taken in mild to moderate HTN, as aggressive blood pressure lowering can compromise fetal circulation. However, the optimal blood pressure to initiate treatment below this threshold is less well defined and should be individualized to the patient including factors like underlying cardiovascular disease and baseline blood pressure.   The timing of delivery is a critical aspect of managing a patient’s hypertension. For a detailed discussion, review the ACOG practice bulletin.   5. How does a hypertensive disorder of pregnancy change a patient’s cardiovascular risk?  A history of a hypertensive disorder of pregnancy is an important risk factor for future cardiovascular disease. These patients are more likely to experience hypertension, ischemic heart disease, heart failure, chronic kidney disease, diabetes, and stroke.   Remember that between 5-10% of pregnancies are complicated by a hypertensive disorder. Given the prevalence and prognostic importance of these disorders, it is crucial to take a detailed obstetrics history when caring for women with cardiovascular disease!  Enjoy prior episodes discussing cardiovascular risk in women:  Ep #18 – Women’s CV Health with Dr. Martha Gulati  Ep #41 – Women’s CV Prevention with Dr. Leslie Cho  Ep #52 – Women’s Heart Health & Women in Cardiology with Dr. Nanette Wenger  References Thilaganathan, B., & Kalafat, E. (2019). Cardiovascular System in Preeclampsia and Beyond. Hypertension (Dallas, Tex. : 1979), 73(3), 522–531.  ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy. (2018). Obstetrics and gynecology, 132(1), e44–e52.   Wenger, N. K., Arnold, A., Bairey Merz, C. N. et al. (2018). Hypertension Across a Woman’s Life Cycle. Journal of the American College of Cardiology, 71(16), 1797–1813.   Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/  Brown, M. A., Magee, L. A., Kenny, L. C. et al. (2018). Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension (Dallas, Tex. : 1979), 72(1), 24–43.   Sanghavi, M., & Rutherford, J. D. (2014). Cardiovascular physiology of pregnancy. Circulation, 130(12), 1003–1008.   Seely, E. W., & Ecker, J. (2011). Clinical practice. Chronic hypertension in pregnancy. The New England journal of medicine, 365(5), 439–446.   Honigberg, M. C., Zekavat, S. M., Aragam, K. et al. (2019). Long-Term Cardiovascular Risk in Women With Hypertension During Pregnancy. Journal of the American College of Cardiology, 74(22), 2743–2754.   Ives, C. W., Sinkey, R., Rajapreyar, I., et al. (2020). Preeclampsia-Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 76(14), 1690–1702.   Duley, L., Meher, S., Hunter, K. E., et al. (2019). Antiplatelet agents for preventing pre-eclampsia and its complications. The Cochrane database of systematic reviews, 2019(10), CD004659.   Ying, W., Catov, J. M., & Ouyang, P. (2018). Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk. Journal of the American Heart Association, 7(17), e009382.   CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join  join UCLA cardiology fellows (Jay Patel, Hillary Shapiro, and Ruth Hsiao) for some beach bonfire in Santa Monica! They discuss a challenging case of Spontaneous Coronary Artery Dissection (SCAD) requiring heart transplantation. Dr. Jonathan Tobis provides the E-CPR and program director Dr. Karol Watson provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Evelyn Song with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A woman in her late 40s presented with a one day history of intermittent chest pain. EKG showed anteroseptal and lateral STE with reciprocal ST depressions in the inferior leads. High-sensitivity troponin was elevated at 333 ng/mL. Emergent LHC showed a long and narrow left main with areas of additional contrast filling into a false lumen with no flow in the LAD. RCA and LCx were normal appearing (make sure you check out the angiogram videos below!). IVUS showed dissection and heavy thrombus burden in the left main artery. Shortly after the diagnostic angiogram, the patient went into V-fib arrest and received one shock with ROSC. Amiodarone was started and an Impella CP was placed for additional left ventricular support. ECMO and emergent CABG were not readily available at this time so the interventional team attempted revascularization with PCI to the left main given patient’s hemodynamic instability from ongoing ischemia. However, even after PCI to left main, flow to LAD remained poor and the LCx now also appeared occluded. The decision was made to cease further attempts at revascularization. Unfortunately, post-procedure TTE showed a reduced EF of 22% with anterior and anterolateral hypokinesis. She was transferred to CCU on maximal Impella support. Patient eventually developed acute renal and liver failure secondary to cardiogenic shock and suffered an additional V-fib arrest with ROSC. Eventually, Ronald Reagan UCLA was contacted for transfer and the mobile ECMO team was dispatched. They placed the patient on VA-ECMO in the outside facility and transferred her to Ronald Reagan UCLA. At Ronald Reagan, revascularization was attempted given persistent cardiogenic shock and 3 stents were successfully deployed in the LAD. She was eventually weaned off of both Impella and ECMO after successful PCIs to LAD. However, TTE showed persistently low EF and patient eventually underwent successful heart-kidney transplantation.  Case Media A B C D Click to Enlarge A. ECG: Anterior STE, STE in I/aVL but depressedions in V4-V6, inferior reciprocal ST depressionB. X-ray of explanted heart shows stents extending from LM -> dLADC. Cross-section of explanted heart from apex to base showing infarct in the anteroseptal areaD. Histological cross section of the explanted LAD.  This film shows slit like LM with no LAD.  High OM/RI and LCx look ok. BMW wire used to cross distal LM into high OM/RIArrested after diagnostic, got ROSC and then Impella CP inserted L femoral Attempting wiring the true lumen, stuck in mLAD after 1st septal comes off IVUS from RI to LM.  Shows dissection plane and lots of thrombusLM IVUS details: 4.57 x 5.0mm proximally, 4.52mm distally Unable to pass a wire into mid LAD PCI of LM: Synergy 4.0 x 16mm DES deployed in LM and post-dilated with Emerge NC 4.5 x 8mm balloon Flow remained poor at mLAD even after PCI to LM LCx system closed after LM PCI, so no further attempts TTE: Apical 4 Chamber TTE: Apical 2 Chamber TTE: Apical 3 Chamber LCx occluded with large OM1/Ramus still patent Post PCI of the LAD Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case What is SCAD and what population is most at risk?  SCAD stands for spontaneous coronary artery dissection. It is an acute coronary event and is defined as a spontaneous separation of the coronary artery wall that is not iatrogenic or related to trauma. It is an important cause of acute myocardial infarction.  Women comprise 87%-95% of SCAD patients with a mean age of presentation between 44-53 years, just like the patient in this case. The “typical” SCAD patient is a middle-aged female with few traditional cardiovascular risk factors such as hypertension, hyperlipidemia, and tobacco use. However, our understanding of a “typical” SCAD patient is limited as the majority of patients in large series have been white and it is likely that patients of different ethnic and racial backgrounds have been under-represented in most current registries.   In some studies, the prevalence of SCAD appears around 4% of all patients presenting with ACS and up to 35% in women 50 years or under presenting with ACS.   Pregnancy associated SCAD is an important subset of patients. It can occur at any time during the pregnancy or post-partum, with the majority of cases occurring postpartum. SCAD associated with pregnancy tends to have a more severe clinical presentation, including left main involvement, multi-vessel dissection and cardiogenic shock. Both pregnancy and non-pregnancy associated SCAD tend to occur more frequently in multiparous women and those that report a higher prevalence of pre-eclampsia.   What are the two hypotheses that have been proposed to explain the pathophysiology of SCAD?  Before reviewing the pathophysiology, let’s briefly review the coronary arterial wall structure. The intima is the inner layer in contact with the intraluminal space. In normal vasculature, the intima is only a few cell layers thick and is separated from the media by the internal elastic lamina. The media is the middle layer and is made up of layers of smooth muscle cells which help regulate vascular tone. The media is separated from the adventitia by the external elastic lamina. Finally, the adventitia surrounds the media and through fibrous connective tissue provides support for the epicardial vessel.   In SCAD, a hematoma forms within the tunica media separating the intima or intima/media from the vessel and compressing the true lumen leading to ischemia. There are several proposed hypotheses for how this occurs:  “Inside-out” hypothesis: an endothelial-intimal disruption or “flap” develops first and then blood enters the sub-intimal space from the true lumen via this “flap”  “Outside-in” hypothesis: a hematoma forms within the media, possibly from disruption of traversing micro-vessels, and compresses and occludes the true lumen as the hematoma expands.   In both hypotheses, the end result is separation of the layers of coronary artery wall, creating a false vs. true lumen. Currently, the evidence favors the “outside-in” theory because in most SCAD cases, there are no communication between the true and false lumens observed.   What are the angiographic appearances of SCAD?  Left anterior descending artery is the most commonly affected vessel in SCAD.  There are three classifications of SCAD based on angiographic appearance (the Yip-Saw classification).   Type 1: Contrast dye staining of the arterial wall demonstrates double or multiple radiolucent lumens separated by a radiolucent flap. There may be dye “hang-up” or slow contrast clearing.   Type 2: This is the most common subtype. It is characterized by long, diffuse, and smooth narrowing that can vary from mild stenosis to complete occlusion, often with abrupt changes in lumen diameter.  Type 2a SCAD demonstrates normal arterial segments proximal and distal to a dissection and does not extend into a distal vessel.   Type 2b does extend into the distal tip of a vessel.   Type 3: The angiographic appearance mimics a focal stenosis of atherosclerotic disease and typically requires intracoronary imaging to make a definitive diagnosis.   There are other angiographic findings that may clue the cardiology team into a diagnosis of SCAD. SCAD tends to affect more distal segments than atherosclerotic disease. Furthermore, the left anterior descending (LAD) artery is the most commonly affected vessel in SCAD. Patients with SCAD tend to have more tortuous vessels and atherosclerotic lesions are usually absent from vessels not affected by the SCAD. Some reports have indicated the external luminal compression by the intramural hematoma (IMH) gives the appearance of a stick insect.   What is the management of SCAD in the acute setting?   As Dr. Hayes et al. note in their JACC review, the focus in the acute setting is to restore perfusion and maintain myocardial function as conservatively as possible rather than on how to restore normal coronary architecture as in atherosclerotic ACS. The use of thrombolytics have resulted in extension of dissection or hematoma and should be avoided. Diagnostic left heart catheterization is recommended but outcomes of PCI in SCAD are less predictable. There are often technical challenges due to the fragility of the vessel wall, instrumentation can propagate a dissection or occlude distal branches, and long-stents may be required as SCAD lesions tend to be extensive and in small distal vessels. Temporal resolution of the IMH may lead to late stent mal-apposition as the IMH reabsorbs.   CABG is typically only considered if PCI has failed or in high risk lesions. Again, the fragility of the vessels makes a successful result challenging. Identifying the true lumen (for graft anastomosis) may be difficult. Sutures may not hold and patients may be prone to anastomotic complications. Over the long-term, healing of the native coronaries may lead to bypass graft failure due to competitive flow into the native system. However, CABG can still be an effective measure to stabilize unstable patients.   Among patients treated conservatively, 95% of patients usually will heal within 30 days; therefore, if there is no ongoing ischemia or hemodynamic instability, instrumentation should be avoided.  In terms of medications, patients with LV dysfunction should receive GDMT (with special attention to teratogenic medications for patients that are pregnant or breastfeeding) and patients undergoing PCI should receive DAPT. In patients that do not receive PCI, the evidence and expert opinion is varying on whether DAPT should be recommended for medical management of ACS.   What’s the long-term management and outcomes for patients with SCAD?  SCAD can be associated with underlying systemic arteriopathy such as fibromuscular dysplasia (FMD) in >50% cases and head/neck aneurysms in 7-11% cases. Patients diagnosed with SCAD should undergo CTA or MRA from head to pelvis to identify additional extra-coronary vascular abnormalities.  Post-SCAD chest pain is common and may occur for many months following the index episode. There can be various triggers of the chest pain, including exercise, stress, or during the menstrual period. Given the increased risk of iatrogenic catheter-induced dissection in post-SCAD patients, a multi-modal evaluation is recommended before considering repeat LHC (e.g., ECG, biomarkers, echo, coronary CTA, stress imaging).  Rates of recurrent SCAD have been reported as 10 to 30%. Secondary prevention for SCAD include avoidance of potential triggers such as stress or extreme exertion and blood pressure control. However, cardiac rehabilitation and moderate exercise’s benefits likely outweigh the theoretical risk of recurrent SCAD with exertion. Beta-blockers may decrease the risk of recurrence but evidence is limited.   There are important considerations for future pregnancy and SCAD. See the JACC review for more details! Another important aspect of post-SCAD care is recognizing the high burden of psychological distress amongst SCAD patients. Clinicians must recognized this early and provide early treatment and appropriate referrals to ensure recovery.   It sounds like the benefits of E-CPR remain to be further elucidated. Are there any specific features that help predict who would benefit from ECPR?   While we do not have high quality randomized data, observational data in EPCR has shown that shorter no flow times (i.e., CPR initiated within 5 minutes of arrest), total duration of CPR <60 minutes, intermittent return of spontaneous circulation, an initial shockable rhythm, and lower serum lactate concentration have been associated with increased survival with better neurologic recovery.  A well-known protocol is the University of Minnesota ECPR protocol (transport with ongoing CPR to the cardiac catheterization laboratory for ECPR) for patients with refractory VT/VF arrest. The inclusion and exclusion criteria for this protocol included  Inclusion: (1) OHCA with presumed cardiac etiology cardiac arrest; (2) first presenting rhythm is shockable (VF or VT); (3) Age 18 to 75 years; (4) Received at least 3 direct current (DC) shocks without sustained ROSC; (5) received Amiodarone 300 mg; (6) Body can accommodate a Lund University Cardiac Arrest System (LUCA) automated CPR device; and (7) Transfer time from the scene to the Cardiac Catheterization Lab of < 30 minutes  Exclusion: (1) ROSC before 3 shocks were delivered; (2) Nursing home residents: (3) DNR/DNI orders; (4) known terminal illness (e.g., malignancy); (5) Traumatic arrest; (6) PEA or asystole; (7) significant bleeding; (8) manual CPR as the only option  Using this strict UMN-ECPR protocol, Bartos et al. retrospectively compared 160 consecutive adult patients with refractory VT/VF arrest treated with ECPR to 654 patients treated with conventional CPR from the amiodarone arm of the ALPS study (Amiodarone, Lidocaine or Placebo study). They found ECPR had favorable survival compared with conventional CPR at each CPR duration interval <60 minutes; however, longer CPR duration was associated with worsening neurologic outcomes and survival in both groups. There remains considerable evidence gaps to define which patient populations would most benefit from this intensive resource.   References Hayes, S. N., Tweet, M. S., Adlam, D., Kim, E., Gulati, R., Price, J. E., & Rose, C. H. (2020). Spontaneous Coronary Artery Dissection: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 76(8), 961–984.  Saw, J., Humphries, K., Aymong, E., Sedlak, T., Prakash, R., Starovoytov, A., & Mancini, G. (2017). Spontaneous Coronary Artery Dissection: Clinical Outcomes and Risk of Recurrence. Journal of the American College of Cardiology, 70(9), 1148–1158.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Houston Methodist cardiology fellows (Isaac Tea, Stephanie Fuentes, Peter Rothstein) for a trip to Hermann Park! They discuss a challenging case of right ventricular (RV) infarction leading to acute RV failure treated with right ventricular assist device (RVAD) support. Dr. Mahwash Kassi provides the E-CPR and program director Dr. Stephen Little provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Tommy Das with mentorship from University of Maryland cardiology fellow Karan Desai.  Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his early 70s with ASCVD risk factors and known CAD (PCI to proximal LAD 4 years prior) presented with typical angina refractory to maximal medical therapy. A nuclear stress test showed a reversible perfusion defect in the RCA territory, and he was referred for PCI. Coronary angiogram showed severe stenosis of the proximal RCA and a DES was successfully deployed with TIMI 3 flow, though several large acute marginal branches were jailed.   The night following PCI, the patient developed bradycardia, hypotension, and tachypnea. Physical exam showed newly elevated JVP, lower extremity edema, and bibasilar crackles without a new cardiac murmur. ECG showed ST elevation in V1-V4, and bedside echocardiogram showed a severely dilated RV with decreased systolic function. With concern for acute RV failure, the patient was fluid resuscitated, started on dopamine for chronotropy, and was admitted to the CCU. A Swan-Ganz catheter was placed, showing a CVP 12, RV 41/15, PA 36/20 (25), PCWP 18, CI 1.6 (by Fick method). The calculated PAPi was 0.84.   The patient was transitioned to dobutamine to improve RV inotropy, epinephrine in the setting of hypotension, and inhaled nitric oxide in an attempt to decrease RV afterload. Despite these interventions, the patient had worsening shock, anuric renal failure requiring CVVH, and respiratory failure requiring intubation. A centrifugal RA to PA pump was placed (Protek Duo) for right-sided mechanical circulatory support, with improvement in RV hemodynamics and cardiogenic shock. Notably, a repeat angiogram was done, which showed a patent left coronary circulation as well as a right coronary artery without flow in the acute marginal branches. After 6 days of mechanical circulatory support, the patient was ultimately able to be weaned from vasoactive agents, and the Protek Duo was removed. He continued to have junctional bradycardia, and a permanent pacemaker was placed. After a nearly month-long admission, the patient was discharged to rehab; at 4 months follow-up, the patient’s RV function had improved on TTE, and he was not limited from heart failure symptoms.   Case Media A B C D E F G Click to Enlarge A: ECG, initialB: ECG: 8 hours post PCI he was noted to have junctional bradycardia with ST-segment elevations in V1-V4.C: Pre and post RCA PCI D: TTE: EF 50-55%, Severely enlarged RV with severely reduced systolic function, TAPSE 1.4 cm, Myocardial systolic excursion velocity (S’): 5.9E: CXR- shock F: Swan, Protek Duo Cannula, Temporary pacer G: CXR and TTE images demonstrating Protek Duo cannula placement Left Coronary System -1 Left Coronary System – 2 Severe eccentric serial stenoses in the proximal to mid RCA – 1 RCA – 2 RCA PCI – 1 RCA PCI – 2 RCA PCI – 3 RCA PCI – 4 RCA – Final TTE -1 TTE -2 Repeat angiogram: Patent stents, sluggish flow Protek Duo Placement Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1) Don’t forget about the RV, because it sure won’t forget about you! Cardionerds, how do you break down the pathophysiology of acute RV failure?  Understanding the pathophysiology of RV failure requires a basic understanding of RV physiology. Normal RV function depends on systemic venous return, RV afterload, pericardial compliance/constraint, and native RV contractility. Remember, the thin-walled RV requires much less energy to generate output compared to the LV as the RV is pumping into the highly compliant, low-resistance pulmonary circulation. Overall, the RV is highly sensitive to changes in RV afterload.  Thus, when we think of acute RV failure, our primary considerations are factors that rapidly increase RV afterload (e.g., pulmonary embolus), as well as conditions with decreased RV contractility (e.g., RV ischemia). The RV is more adept to tolerating changes in volume rather than pressure (since it is coupled to the low-resistance, high compliance pulmonary circulation). Contrast this with the LV, which tolerates changes in pressure more than volume. An acute increase in RV afterload can abruptly precipitate a fall in RV cardiac output!  With an acute decreased in RV contractility (e.g., RV infarct), the RV can dilate leading to functional TR; this can further exacerbate RV dilation, leading to impaired LV filling due to ventricular interdependence. As the septum shifts leftward, this can impair LV filling by increasing LVEDP and lead to hypotension. Direct RV injury can promote more RV injury/ischemia, as elevated right heart pressures can cause coronary sinus congestion reducing coronary blood flow and leading to more RV ischemia.  For more detailed explanation of Right-Sided Heart Failure, see this fantastic Scientific Statement from the AHA!  2) Lets focus on ischemic RV disease: what is the coronary supply to the RV, and how does coronary blood flow to the RV differ than that of the LV?  Compared to the LV, the RV is more resistant to irreversible ischemia. Coronary blood flow to the RV occurs both in systole and diastole, RV myocardial oxygen demand at rest is lower than that of the LV with smaller muscle mass, and there is often extensive collateral circulation from the left coronary system. However, RV coronary perfusion pressure can decrease rapidly in the setting of systemic hypotension and increased RV intracavitary pressure.   In most patients, the RV is supplied by the RCA via RV acute marginal branches largely supplying the anterior RV free wall. Significant RV involvement in an RCA culprit acute myocardial infarction tends to only occur if the occlusion is proximal to the acute marginal branch. Furthermore, the extent of RV involvement may be attenuated by the amount of left to right collateralization.   Note, the LAD supplies the RV apex, as well as a portion of the RV anterior wall that is contiguous with the anterior septum. Notably, in patients with a left dominant coronary system or in patients with a chronically occluded RCA with extensive left to right collateral flow, more than half of the RV free wall may be supplied by the left system.  3) Now that we know what causes acute RV failure, what can we do to assess for acute RV failure, both at the bedside and with advanced diagnostics?  Physical exam: In acute RV failure, we will likely see elevated neck veins +/- Kussmaul’s sign, hypotension, possibly clear lungs depending on etiology, and tricuspid regurgitation murmur. Enjoy Ep #58 – Constrictive Pericarditis CN5 for more details on right-sided exam findings!  ECG: Unfortunately, the standard 12-lead ECG provides limited definitive information on RV failure. However, we should evaluate for acute occlusive myocardial infarction (MI) involving the RV, including ST elevation in the inferior leads (classically with III > II), V1 > V2, and/or V1 +/- ST depression in V2. Right-sided leads can further confirm acute occlusive MI, with STE > 1mm in lead V4R sensitive and specific for RV infarct. With a large RV infarct, we may see brady-arrhythmias. Other signs of acute RV failure may include RV strain pattern (e.g., ST depression and T wave inversions in V1-V3). Enjoy Ep #60 – Massive PE for more on ECG changes in acute PE and RV failure!  CT: While usually not obtained in the setting of acute RV failure unless evaluating for acute PE or parenchymal lung disease, RV:LV ratio >1.0, pulmonary trunk enlargement, and contrast reflux into the inferior vena cava and hepatic veins suggest right heart failure. A gated cardiac contrast-enhanced CT can provide more information about chamber size/function and valvular pathology.  TTE: Echo is crucial in the diagnosis of RV failure! One of the first things to pay attention to is RV size, with RV dilation being a poor prognostic sign; RV:LV ratio > 1 is associated with increased in-hospital mortality in some studies of acute PE patients. Evaluate the position of the interventricular septum, which may be flattened in systole suggestive of RV pressure overload and/or in diastole suggestive of volume overload. RV systolic function can be assessed by tricuspid annular plane systolic excursion (TAPSE) which is a marker of longitudinal myocardial shortening with abnormal being less than 1.6 cm. There are limitations to use of TAPSE, but it remains a relatively specific test for RV dysfunction. An estimation of pulmonary artery systolic pressure (PASP) should be done utilizing the TR jet; however, in the setting of severe TR, the doppler envelope is often low velocity and early peaking because of high RA pressure making PASP difficult to estimate. The IVC should be evaluated for size, response to respiration and hepatic vein reversal. There are many more aspects to review regarding acute RV failure and RV systolic function like fractional area change, tissue doppler velocity, and RV strain (see the references below!), but also remember to evaluate for specific pathology, including signs of acute PE such as McConnell’s sign.  RHC: In the setting of acute right heart failure, a right heart catheterization may be necessary to guide therapy. An elevated right atrial pressure, and specifically an elevated right atrial pressure to pulmonary capillary wedge pressure ratio can be indicative of right heart failure; the specific ratio depends on disease state, but generally >0.6 to 0.8 suggestive of RV failure. PA pulsatility index (PAPi) has become a useful tool in evaluating for RV failure specifically in the setting of acute myocardial infarction. An abnormal value depends on disease state as RV pulsatility is not only a function of RV function, but also pulmonary vascular resistance and capacitance.  4) So, what’s the big deal? How does acute RV failure cause shock?  Decreased RV cardiac output, combined with a dilated RV, leads to interventricular septal shift towards the left, compromising LV filling (preload) as discussed above. Decreased LV preload eventually leads to decreased LV cardiac output and hypotension, causing end-organ damage and decreased coronary perfusion. Elevated right-sided filling pressures with systemic venous congestion can lead to hepatic and renal congestion, exacerbating fluid retention. Decreased coronary perfusion can leads to decreased oxygen delivery to a failing RV that already has a higher oxygen demand (due to increased RV afterload and wall tension). This, ultimately can cause further RV ischemia and collapse in RV function. This physiologic phenomenon is referred to as the RV Spiral of Death.   5) Yikes! What can we do to break this spiral and medically manage RV failure? Is there a role for mechanical support?  Correct the initial insult to the RV! As we take measures to support the RV, we have to ensure we evaluate for the etiology of RV failure and treat the underlying cause. This includes PCI in the setting of RVMI, anticoagulation/thrombolysis/thrombectomy in the setting of PE, and medical management in the setting of sepsis!  Address preload! Remember, not all RV failure is created alike. An acute RV infarct may be highly pre-load dependent and may need fluid boluses. However, depending on the underlying pathology, excessive preload may be detrimental, leading to excess wall stress and RV dilation, which can potentially exacerbate left-ward septal shift and impede LV filling. Ventricular interdependence as a result of RV dilation and pericardial constraint may play a larger role in worsening acute RV failure than decreased RV ejection fraction, and thus decompression of the RV is necessary (e.g., diuretics, renal replacement therapy), as guided by exam +/-  RHC.  Reduce RV afterload! First, address reversible factors leading to pulmonary vasoconstriction including hypoxia and acidosis. In patients receiving positive pressure ventilation, PEEP should be optimized to avoid atelectasis, while also avoiding over distension of alveoli and worsened RV afterload. Non-selective systemic vasodilators (e.g., intravenous sodium nitroprusside > nitroglycerin) decrease systemic and pulmonary vascular resistance, and thus decrease LV and RV afterload. Selective pulmonary vasodilators, such as inhaled nitric oxide and epoprostenol can also be effective in specific patient populations.   Improve Contractility and Maintain Perfusion! Dobutamine and milrinone both improve RV inotropy at the cost of arrhythmogenicity. Both agents can also lead to vasodilation and thus whether hypotension worsens may depend on how effectively these agents assist in augmenting LV preload compared to systemic vasodilation. In the setting of hypotension, combined vasopressor and inotropic medications may be needed including norepinephrine and/or epinephrine. With escalating doses of vasoactive medications, vasopressin may be needed to maintain end-organ perfusion.   Assess chronotropy! RV infarcts increase the risk of bradycardia and AV block. Temporary pacing may be necessary in these patients.   In refractory acute RV failure, consider mechanical support! There are 3 main options for temporary RV mechanical support:   VA-ECMO substantially reduces RV preload and afterload, though it can dramatically increase LV afterload VA ECMO is an indirect way to bypass the RV compared to MCS below.   RA to PA extracorporeal pump (ex. Protek Duo and Tandem Heart RVAD) removes blood from the RA and delivers it into the PA using a centrifugal pump and an oxygenator can be added if needed. RV preload is reduced while increasing mean PA pressure and LV preload.  Micro-axial flow device (e.g., Impella RP) with an inflow in the RA and an outflow in the PA.  References Koo, B. K., Kang, H. J., Youn, T. J., et al. (2005). Physiologic assessment of jailed side branch lesions using fractional flow reserve. Journal of the American College of Cardiology, 46(4), 633–637.  Fincke, R., Hochman, J. S., Lowe, A. M., et al. (2004). Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. Journal of the American College of Cardiology, 44(2), 340–348.  Kapur, N. K., Esposito, M. L., Bader, Y., et al. (2017). Mechanical Circulatory Support Devices for Acute Right Ventricular Failure. Circulation, 136(3), 314–326.   Konstam, M. A., Kiernan, M. S., Bernstein, D., et al. (2018). Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association. Circulation, 137(20), e578–e622.   Jeffers JL, Boyd KL, Parks LJ. Right Ventricular Myocardial Infarction. [Updated 2020 Aug 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431048/  Sanz, J., Sánchez-Quintana, D., Bossone, E., et al. (2019). Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 73(12), 1463–1482.   Korabathina, R., Heffernan, K. S., Paruchuri, V., et al. (2012). The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, 80(4), 593–600.   CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Florida cardiology fellows (Ashley Mohadjer, Hussain Khalid, and Morgan Randall) for an authentic Gainesville-style tailgate! They discuss a fascinating case of severe peripheral artery disease (PAD) and cerebral hyperperfusion syndrome. Dr. Khanjan Shah provides the E-CPR and  a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Richard Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A woman in her 60s with a past medical history of type 2 diabetes, hypertension, and hypothyroidism presented to the University of Florida with a chief complaint of “Someone told me my neck artery was blocked.”  Someone call 227-346-6373.  What does that spell? CardioNerd!    She noted exertional pain in both legs with limited exertion. Has a family history of CAD and MI in her father in his 20s. Her only medications were baby aspirin, atorvastatin 80mg, and thyroid replacement. Her blood pressures were noted to be dropping and so her regimen was being titrated off as a result. Physical exam was notable only for poorly palpable pulses in all extremities. To further work this up, a myocardial perfusion scan, CTA head/neck/abdomen, and ABIs were ordered. ABI on the right was 0.86 and on the left was 0.76 with monophasic doppler waveforms throughout. CT abdomen exhibited an occlusion of the abdominal aorta from just below the renal arteries extending to the common iliac arteries with distal reconstitution. CT head/neck showed occlusion of the right carotid artery, complete occlusion of the right innominate artery, near complete occlusion of the right vertebral artery, and delayed flow in the right posterior cerebral artery. On the left side, she had high-grade subclavian stenosis. Myocardial perfusion imaging exhibited no defects.   On subsequent visits her exercise tolerance improved with an exercise regimen, but blood pressures were more and more difficult to obtain. As a result, revascularization was pursued with stenting of the left subclavian artery. She was discharged, but returned a few hours later with severe left sided pulsatile headache and nausea/vomiting. She was admitted for monitoring, but fortunately improved and discharged with close outpatient follow-up.  She continued to improve in the outpatient setting. After MRI brain and extensive work-up, she was deemed to have cerebral hyperperfusion syndrome following revascularization.  She had no further complications and was monitored thereafter.  Final diagnosis: severe peripheral artery disease (PAD) and cerebral hyperperfusion syndrome. Case Media A B C D E F Click to Enlarge A: ECG B: ABIsC: CT Angiogram D: CT Angiogram – head and neck E: Pre and post subclavian stentinng F: CT head and neck – follow up Subclavian via L radial Aortic Root Cine 1 Aortic Root Cine 2 Stent Post Stent Post Stent 2 Post Stent 3 Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case What are the risk factors and prevalence of PAD?  PAD refers to atherosclerotic peripheral artery disease, and is the accumulation of plaque in various peripheral arterial beds akin to CAD involving coronary arteries.  6% of adults over the age of 40 have PAD, and 30% of American adults over the age of 70. This all leads to an annual healthcare expenditure in the US of ~$4 billion! PAD is associated with a 3-4x increased risk of cardiovascular events.  Furthermore, mortality overall is 15-20% at 5 years in patients with PAD.   Risk factors for PAD include all the risk factors for ASCVD we consider for CAD, including diabetes, hypertension, and hyperlipidemia.   What Should We Look for on Physical Exam with PAD?   Get a brachial blood pressure (Class Ib AHA/ACC Recommendation), listen for bruits (areas of turbulent flow), and look at the extremities for: skin color changes, temperatures changes, loss of hair, or ulcerations (typically at the tips of digits). In patients with claudication and/or risk factors for PAD, these can all be signs of PAD.  In particular, palpate the dorsalis pedis and tibialis pulses.   In office maneuvers can also include Buerger’s test where the affected limb is elevated from a supine position till pallor is observed. In a normal limb, even elevating to 90 degrees should not elicit pallor; however, in an ischemic limb, especially severe ischemia, elevation to even 20 degrees for 30 to 60 seconds can lead to pallor. Then when returning the limb to resting position, the pink color will return slowly (I.e., >20 seconds) and may demonstrate rubor as there is reactive hyperemia (dilation of the arterioles) in attempt to remove metabolic waste and restore circulation.   At the bedside, we should also test for diseases commonly associated with PAD, particularly diabetes. Testing for diabetic neuropathy is critical in patients with PAD, as it is a modifiable risk factor and can make patients prone to developing diabetic foot ulcers.   Remember, that there are classic locations for arterial ulcers but often patients have a mixed picture given concomitant venous insufficiency and/or diabetes. These arterial ulcers tend to occur where arteries terminate, including between the digits and tips of the toes. Furthermore, they can occur at areas of increased pressure, including the lateral malleolus.  How do we obtain and interpret ABIs in chronic limb ischemia?  ABI stands for Ankle-Branchial Index. This means taking the ankle blood pressure and indexing it against the brachial blood pressure.  The ABI is an easily done test. To ensure we have an accurate ABI, we typically ask the patient to rest for at least 5-10 minutes prior to measuring ankle pressure. We also want to make sure we have the appropriate cuff size, and thus in the limbs the cuff width should be at least 40% of the limb circumference.  We can start by taking the brachial pressure in one arm. After obtaining our initial brachial SBP, we then proceed with taking a blood pressure from either the dorsalis pedis or posterior tibial artery on the same side, with the cuff just above the ankle. We utilize a continuous wave doppler signal to identify the pulse and insufflate the cuff to just above where the Doppler signal disappears.  We then slowly release the pressure in the cuff and record where the systolic pressure returns and repeat the process for the artery (e.g., DP or PT) that was not tested and then move onto to the contralateral limb. We then finally obtain the SBP in the brachial on the side opposite from where we started. The ABI for a specific extremity is then the highest pressure in a lower extremity limb (DP or PT) divided by the highest systolic brachial pressure in either limb.   As discussed above, we usually calculate the ABI at bedside using a continuous-wave doppler probe, but when blood pressures are low or if there is significant venous congestion leading to pulsatile flow (e.g., congestive heart failure), the venous signal can be difficult to distinguish from the arterial signal.   Briefly, a normal ABI is considered 1.0 to 1.4; 0.91 to 0.99 is considered borderline; and <0.9 and >1.4 are considered abnormal. In patients with symptoms of PAD (e.g., claudication), ABI has a sensitivity of ~ 95% and specificity of 100% of diagnosing lesions with >50% stenosis in one or major lower extremity vessels. An ABI > 1.4 suggests the presence of calcified vessels and we need additional vascular studies, such as measurement of the toe brachial index (TBI) or pulse volume recordings (PVR) to assess for significant PAD. The vessels in the toe have been shown to be less prone to medial calcification.  Finally, segmental brachial index measurements are also considered abnormal if there is a decrease in 20 mmHg or more between adjacent levels in the lower extremity, a decrease in segmental brachial index of 0.15 or more over time, or a difference in systolic pressure more than 30 mmHg between contralateral limbs.   How Do We Treat Symptomatic PAD?  Exercise! First and foremost, supervised treadmill exercise training is a Class Ia recommendation from the AHA/ACC guidelines. Multiple studies have shown exercise to be beneficial in improving time and distance to developing claudication symptoms and increasing pain-free walking distance up to 180%. Notably, an exercise trial is recommended prior to any attempted revascularization.    As with CAD, lifestyle measures to mitigate ASCVD risk factors are vital, including diet, weight loss, and smoking cessation. Statins are a key to medical management (Class Ia recommendation).  In symptomatic PAD or asymptomatic PAD but with positive ABIs, the general recommendation is to start low dose aspirin (versus P2Y12 monotherapy). There is increasing data exploring the role of DOAC + Aspirin, and generally the addition of low dose DOAC improves morbidity in PAD but at the expense of increased bleeding events.  If there is no or minimal improvement with conservative management, including exercise, a trial of  cilostazol, a phosphodiesterase 3 inhibitor, should be considered as it has been shown to increase walking distance and claudication symptoms (Class Ia). However, note that cilostazol is contraindicated in patients with congestive heart failure per the FDA, though in practice we especially avoid the medication in patients with NYHA Class III-IV heart failure.   When Should We Revascularize?   Revascularization is generally recommended if the patient with chronic limb ischemia remains symptomatic despite guideline-directed medical therapy and conservative lifestyle management (Class IIa). There are separate recommendations for patients with acute or chronic limb-threatening ischemia. Endovascular revascularization is further recommended for patients with symptomatic claudication and hemodynamically significant aortoiliac disease (Class Ia) and can be considered with hemodynamically significant femoropopliteal disease (Class IIa). In patients with non-healing wounds or gangrene, surgical revascularization is recommended to re-establish blood flow (Class Ic-LD).   References Beckman, J. A., Ansel, G. M., Lyden, S. P., & Das, T. S. (2020). Carotid Artery Stenting in Asymptomatic Carotid Artery Stenosis: JACC Review Topic of the Week. Journal of the American College of Cardiology, 75(6), 648-656.  Huibers, A. E., Westerink, J., de Vries, E. E. et. al. (2018). Editor’s choice–cerebral hyperperfusion syndrome after carotid artery stenting: a systematic review and meta-analysis. European Journal of Vascular and Endovascular Surgery, 56(3), 322-333.  Gerhard-Herman, M. D., Gornik, H. L., Barrett, C. et. al. (2017). 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary. Vascular Medicine, 22(3), NP1-NP43.  Aboyans, V., Ricco, J. B., Bartelink, M. L. E., Björck, M. et. al. (2018). 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular …. European heart journal, 39(9), 763-816.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Johns Hopkins Hospital cardiology fellows (Rick Vakil, Pranoti Hiremath, and Vasanth Sathiyakumar) for some gelato by the bay in Baltimore, Maryland! They discuss a challenging case of RV failure & shock after placement of an AV graft. Dr. Monica Mukherjee provides the E-CPR and program director Dr. Steven Schulman provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his early 40s, with a history of type 1 diabetes and prior failed renal and pancreatic transplants currently on iHD, was referred to Johns Hopkins Hospital for dialysis access. A left groin AV loop graft was pursued due to multiple access point failures in the past secondary to severe peripheral artery disease. Pre-op evaluation included risk stratification with RHC which was consistent with WHO Group 2 pulmonary HTN and diffuse atherosclerosis in the RCA on LHC. Intra-op, patient had an episode of significant hypotension after administration of protamine that required phenylephrine and ephedrine. In the PACU, his BPs continued to be low (70s/40s mmHg), requiring admission to the SICU where cardiology was consulted.  In the SICU, patient had ongoing hypotension despite pressors and fluids. Exam demonstrated a systolic murmur consistent with TR and elevated JVP. Labs were notable for a mild elevation in liver enzymes, elevated troponin, high NT-proBNP and elevated lactate. TTE demonstrated a moderately dilated and hypokinetic RV, elevated RVSP and evidence of pressure/volume overload. CTA abdomen/pelvis demonstrated extensive mesenteric atherosclerosis and signs of gastric ischemia. Patient was treated for RV failure with norepinephrine, inhaled epoprostenol, and CVVHD for volume removal. He became febrile and was treated empirically with broad spectrum antibiotics. Due to concern for the new loop graft causing high output heart failure vs RV failure, it was temporarily occluded for testing and then permanently ligated by vascular surgery with significant improvement in his BPs and RV function on repeat TTE.  Case Media A B C D E Click to Enlarge A. Plato’s allegory of the cave by Jan Saenredam, according to Cornelis van Haarlem, 1604, Albertina, ViennaB-C. Anesthesia flow sheets D. CXR: Pulmonary vascular congestion, bibasilar atelectasisE. ECG: Sinus tachycardia to 110, RAD, RBBB, similar to prior TTE: LVEF 60-65%, mild to moderate concentric hypertrophy, trace effusion TTE: Flattened septum in systole and diastole c/f RV pressure and volume overload. RV moderately dilated and hypokinetic. RVSP 63 mmHg. CT Abdomen and Pelvis: Negative for PE, gastric pneumatosis, air within the gastroepiploic veins, and portal venous gas, most concerning for gastric ischemia, extensive atherosclerotic calcifications throughout the mesenteric vessels TTE follow up: Mild/moderate concentric hypertrophy, EF 60%,  G2DD TTE follow up: RV mildly dilated and mild global hypokinesis of the RV. TAPSE 1.54. RV S’ was 9.6 cm/s (normal > 9.5) Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. In this case the patient became hypotensive shortly after administration of protamine. What are the risk factors for a protamine reaction and the proposed mechanisms?  Protamine is a protein commonly used in cardiovascular procedures to reverse the effects of heparin. Although rare, it can cause severe reactions that have multiple different proposed mechanisms. They include hypotension mediated by histamine release from mast cells and IgE-mediated anaphylaxis. Other proposed mechanisms include acute severe pulmonary hypertension with or without RV failure mediated by complement and thromboxane A2 and fulminant noncardiogenic pulmonary edema likely through a thromboxane-mediated process.  Risk factors for protamine reactions have been difficult to rigorously prove, but might include patients with a true fish allergy (Protamine is produced from the sperm of salmon or similar species), men s/p vasectomy (disruption of blood-testes barrier and sensitization against sperm), insulin dependent diabetic patients taking NPH insulin (protamine is used in NPH), and previous exposure to protamine  2. Our patient had signs of RV failure clinically and on TTE following AV graft creation. How common is this, what is the mechanism, and when might one consider avoiding fistula or graft creation in a patient with CHF?   AV fistulas (AVF) are the preferred chronic iHD access due to reductions in infections, morbidity, and mortality compared to central venous access. However, this data is based on observational studies.   Remember, changes in hemodynamics occur in phases following creation of AV hemodialysis access. Acutely, an AVF or prosthetic graft (AVG) decreases systemic vascular resistance (SVR) through a surgical arterial to venous shunt. This acute decrease in SVR leads to increased stroke volume and a decrease in blood pressure. The decrease in SVR activates the sympathetic nervous system and leads to increased HR and combined with the increased SV, an increase in cardiac output.  The increased cardiac output leads to increased right sided venous return and sub-acutely can lead to progressively increasing left and right sided filling pressures. Eventually, there can be worsening RV dilation and systolic dysfunction, elevated pulmonary artery pressures, and myocardial remodeling.  Retrospective analyses have shown that creation of an AVF/AVG can increase the prevalence of RV dilation and dysfunction by 2-3 fold in patients with ESRD.  The risk of worsening heart failure in patients with pre-existing cardiac disease is generally related to the flow in the AV access. Some small studies have suggested there is increased risk of developing heart failure in patients with an upper-arm AV fistula compared with a forearm fistula  Although there are not clear guidelines that dictate when a patient should not receive an AVF/AVG, a permanent dialysis catheter should be considered as an alternative option in patients with pre-existing heart failure or pulmonary hypertension due to increased risk of right heart failure.  3.  AV vascular access can lead to high output heart failure. What is high output heart failure and what are the major mechanisms?   Most CHF occurs in the setting normal or low CO. However, certain conditions can precipitate high output heart failure (HoHF). The underlying pathophysiologic change in HoHF seems to be disproportionately low SVR +/- increased oxygen consumption. The low SVR leads to decreased afterload, increased LV emptying and thus increased stroke volume and cardiac output. Furthermore, this leads to increased cardiac preload. Increased oxygen demand also requires increased cardiac output.  The persistently low SVR causes low renal perfusion pressure (renal hypoperfusion) which leads to RAAS activation and volume expansion. Combined with the increased preload, this can lead to heart failure in susceptible individuals.  Obesity (the most common etiology), AV fistulas (congenital or acquired), cirrhosis, and Paget’s disease lead to HoHF predominantly due to systemic vasodilation. Lung disease, myeloproliferative disorders, and hyperthyroidism can cause HoHF and have a proportionally larger contribution from increased metabolic demand and therefore increased oxygen consumption. Lower SVR has been associated with higher mortality.  4. How might someone differentiate high output heart failure from low output heart failure or RV failure?   RHC is the gold standard to diagnose high output heart failure. Characteristic features include an elevated CO or CI (CI ≥4 L/min/m2) and a low SVR in the setting of clinical signs of heart failure. In a Mayo Clinic study of patients with CI > 4 L/min/m2 with or without signs of heart failure, a CI ≥3.54 L/min/m2 estimated by TTE identified HoHF patients with 62% sensitivity and 96% specificity. Furthermore, patients with HoHF frequently demonstrated doppler-estimated RV systolic pressure ≥ 42 mmHg (92% sensitivity and 100% specificity).  5. After temporary occlusion of his loop graft, our patient had improvement of his blood pressure and a decrease in his HR. What does this indicate and how is it mediated?    A rapid rise in BP and decrease in HR after occlusion of an AVF/AVG is called the Nicoladoni-Branham sign and indicates a hemodynamically significant AV fistula that could benefit from ligation in the right clinical context. Similar to the Bezold-Jarisch reflex, this is thought to be mediated by mechano-, baro-, and chemoreceptors in the LV and vasculature. The high output state leads to increased shear stress and elevated nitric oxide (NO) production. When the shunt is occluded, there is a rapid increase in afterload. Consequently, there is a decrease in cardiac output and preload. The rapid increase in afterload is thought to trigger high-pressure baroreceptors causing bradycardia, while the reduction in preload triggers low-pressure baroreceptors causing vasoconstriction. Additionally, rapid reduction in CO could also lead to vigorous contraction of the LV stimulating mechanoreceptors (leading to further reflex bradycardia) and reduction in NO production, leading to less vasodilation. Thus the net result is bradycardia and relative hypertension.  References Alkhouli, M., Sandhu, P., Boobes, K., Hatahet, K., Raza, F., & Boobes, Y. (2015). Cardiac complications of arteriovenous fistulas in patients with end-stage renal disease. Nefrología (English Edition), 35(3), 234–245.  Clinical Practice Guidelines for Vascular Access. (2006). American Journal of Kidney Diseases, 48, S176–S247.  Park, K. W. (2004). Protamine and Protamine Reactions. International Anesthesiology Clinics, 42(3), 135–145.  Protamine. (1998). Journal of Allergy and Clinical Immunology, 101(6), S507–S509.  Reddy, Y. N. V., Melenovsky, V., Redfield, M. M., Nishimura, R. A., & Borlaug, B. A. (2016). High-Output Heart Failure: A 15-Year Experience. Journal of the American College of Cardiology, 68(5), 473–482.  Reddy, Y. N. V., Obokata, M., Dean, P. G., Melenovsky, V., Nath, K. A., & Borlaug, B. A. (2017). Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease. European Heart Journal, 38(24), 1913–1923.  Schmidli, J., Widmer, M. K., Basile, C., de Donato, G., Gallieni, M., Gibbons, C. P., Haage, P., Hamilton, G., Hedin, U., Kamper, L., Lazarides, M. K., Lindsey, B., Mestres, G., Pegoraro, M., Roy, J., Setacci, C., Shemesh, D., Tordoir, J. H. M., van Loon, M., … Roca-Tey, R. (2018). Editor’s Choice – Vascular Access: 2018 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). European Journal of Vascular and Endovascular Surgery, 55(6), 757–818.  Velez-Roa, S., Neubauer, J., Wissing, M., Porta, A., Somers, V. K., Unger, P., & van de Borne, P. (2004). Acute arterio-venous fistula occlusion decreases sympathetic activity and improves baroreflex control in kidney transplanted patients. Nephrology Dialysis Transplantation, 19(6), 1606–1612.  Wattanasirichaigoon, S., & Pomposelli, F. B. (1997). Branham’s sign is an exaggerated Bezold-Jarisch reflex of arteriovenous fistula. Journal of Vascular Surgery, 26(1), 171–172.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Medical College of Wisconsin cardiology fellows (Katie Cohen, Div Mohananey, and Dave Lewandowski) for some cold brews by Lake Michigan in Cream City aka Milwaukee, WI! They discuss a case of a pregnant woman presenting cardiac arrest due to peripartum cardiomyopathy. Dr. Sarah Thordsen provides the E-CPR and program director, Dr. Nunzio Gaglianello, provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident, Eunice Dugan, with mentorship from University of Maryland cardiology fellow Karan Desai.   Jump to: Patient summary – Case media – Case teaching – References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A G2P1 woman in her early 30s with a history palpitations presented after a witnessed out-of-hospital cardiac arrest while at work. She received 6 rounds of CPR and 2 shocks before ROSC was achieved. She was intubated and given fluids but continued to remain hypoxic and hypotensive. Exam demonstrated sinus tachycardia, no murmurs, gravid abdomen and cool extremities. Initial labs demonstrated leukocytosis to 14k, lactic acid at 4.3 mmol/L, troponin-I peak at 0.07 ng/dL and elevated NT-proBNP. CXR demonstrated bilateral effusions and pulmonary congestion, and post-arrest EKG showed a wide complex tachycardia, leading to suspicion of VT arrest. In sinus, there  were no ST segment elevations and TTE showed LVEF 10-20%, global hypokinesis and no valvular disease. Given the severity of her shock, she was placed on central VA-ECMO with Impella support as an LV vent. During ECMO cannulation, she underwent emergent cesarean section due to fetal distress. Coronary angiography showed non-obstructive coronaries, but with sluggish flow in the setting of her cardiogenic shock and possible coronary spasm in setting of multiple vasoactive medications. Endomyocardial biopsy was negative for giant cell myocarditis. Within 4-5 days, she was weaned off all vasoactive agents and ECMO was decannulated; repeat echocardiogram showed LV functional recovery. GDMT was slowly titrated and a subcutaneous ICD was eventually placed before discharge. She and her child have done well over the course of a year!  Case Media A B Click to Enlarge A: ECG: Initially in sustained wide complex irregular tachycardiaB: CXR: Extensive consolidative changes throughout the lungs TTE: Parasternal Long Axis TTE: Apical 4 Chamber Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case 1. What is the differential for cardiac arrest in pregnant patients?  When thinking about a cardiac etiology of arrest, the differential should include pregnancy-induced hypertension, peripartum cardiomyopathy, myocardial infarction from acute coronary syndrome or spontaneous coronary artery dissection, pulmonary embolism, amniotic fluid embolism and aortic dissection. Non-cardiac etiologies include hemorrhagic shock, sepsis, stroke, trauma and anesthetic complications. In addition to these unique considerations, pregnant patients are also susceptible to the usual culprits!  As noted in the 2015 AHA Scientific Statement, cardiac arrest in pregnancy is not common, occurring in 1:12,000 admissions for delivery. As of 2016, per the CDC the pregnancy-related mortality rate was ~17 deaths per every 100,000 live births. However, mortality data does not fully capture critical illness in pregnancy, and thus the AHA recommends considering maternal “near-miss” data.   Knowledge gaps, provider unfamiliarity, and lack of medical ward or medical/cardiac ICU preparation for cardiac arrest in pregnancy may contribute to morbidity and mortality.   Finally, as many of the early warnings signs of impending cardiac arrest may overlap with symptoms of pregnancy (e.g., progressive dyspnea), early interventions may be delayed. Thus, the AHA recommends using a validated obstetric early warning score to risk stratify ill pregnant patients.   2. Remind us of some important physiologic changes in pregnancy that can affect cardiopulmonary resuscitation   Hormonal and physiologic changes during pregnancy make pregnant patients more prone to hypoxia, hypotension, pulmonary edema, and difficult airway intubation.  Systemic vascular resistance typically decreases due to the production of endogenous vasodilators, though there are important differences in patients with pre-eclampsia. The enlarging uterus can reduce preload by compressing the IVC and increase afterload by compressing the aorta. In the supine position, which is preferable for resuscitation, this compression can be exacerbated.  Furthermore, as the uterus enlarges and limits diaphragmatic movement, functional residual capacity can decrease by 10-25%. At the same time, there is increased oxygen consumption due to metabolic and fetal demands. With limited reserve and increased oxygen demands, hypoventilation or apnea can rapidly precipitate hypoxemia.   Cardiac output increases by 30-50% via increased stroke volume, and lesser extent HR, leading to increased circulating volume, making patients prone to pulmonary edema.   Finally, pregnancy hormones can lead to airway edema and more friable tissue making intubation more difficult with increased risk of bleeding.   For more on pregnancy physiology, enjoy:   Ep #48 – Critical Bicuspid Aortic Valve Stenosis Complicating Pregnancy   Ep # 57 – Peripartum Cardiomyopathy with Cardiogenic Shock  3. What are some aspects unique to advanced cardiac life support (ACLS) in pregnant patients?  Cardiac arrest is inherently different than other cardiac arrest that we typically encounter as there are two patients: mother and the fetus.   Chest compressions, delivery of shocks and medications can continue per standard adult ACLS algorithm.   Importantly, while chest compressions are ongoing and patient is in the supine position, there should be continuous manual left uterine displacement (LUD) to relieve aortocaval compression. Furthermore, IVs should be established above the diaphragm so that intravenous infusions and medications are not impeded by caval compression of the uterus.  Teams should be prepared for perimortem caesarean delivery (PMCD) and this should occur at the site of arrest. PMCD may facilitate return of spontaneous circulation (ROSC) after the gravid uterus is emptied.  PMCD should occur within four minutes due to a rapid decline in fetal survival with longer delays to delivery.   4. What are the considerations for post-arrest care for pregnant patients?  Targeted temperature management (TTM) is not contraindicated in pregnancy, and no necessary intervention should be withheld for fear of fetal damage. The primary focus should be maternal outcomes since that best serves fetal outcomes.  If TTM is pursued, there should be continuous fetal monitoring. The patient should continue to be in the left lateral decubitus position if it does not compromise other management. Routine cardiac catheterization is certainly not recommended unless post-arrest EKG demonstrates clear signs of ischemia.  Remember that embryogenesis is mostly complete by 12 weeks of gestation. Thus, the AHA recommends providing all necessary medications, even teratogenic medications (e.g., corticosteroids, phenytoin) especially if the cardiac arrest occurs after the first trimester.   5. What is the data for extra-corporeal life support (ECLS) during pregnancy and postpartum  There are no consensus guidelines, however, ECLS is not contraindicated in pregnancy and should be considered for life-threatening conditions. There is lack of long-term data for maternal and fetal outcomes.   Although survival varied depending on indication, one systematic review of ECLS in peripartum patients showed overall 30-day survival of 75% for mother and 64% for fetus. Interestingly, survival in the immediate post-partum group was the highest.  Complications includes bleeding, deep vein thrombosis, and vascular complications similar to the non-pregnant population.   References Arany Zolt, and Elkayam Uri. “Peripartum Cardiomyopathy.” Circulation 133, no. 14 (April 5, 2016): 1397–1409. Campbell, Tabitha A, and Tracy G Sanson. “Cardiac Arrest and Pregnancy.” Journal of Emergencies, Trauma and Shock2, no. 1 (2009): 34–42.  Jeejeebhoy Farida M., Zelop Carolyn M., Lipman Steve, Carvalho Brendan, Joglar Jose, Mhyre Jill M., Katz Vern L., et al. “Cardiac Arrest in Pregnancy.” Circulation 132, no. 18 (November 3, 2015): 1747–73.  Gilotra, Nisha A, and Gerin R Stevens. “Temporary Mechanical Circulatory Support: A Review of the Options, Indications, and Outcomes.” Clinical Medicine Insights. Cardiology 8, no. Suppl 1 (February 3, 2015): 75–85.  Naoum Emily E., Chalupka Andrew, Haft Jonathan, MacEachern Mark, Vandeven Cosmas J. M., Easter Sarah Rae, Maile Michael, Bateman Brian T., and Bauer Melissa E. “Extracorporeal Life Support in Pregnancy: A Systematic Review.” Journal of the American Heart Association 9, no. 13 (July 7, 2020): e016072.  Sharma, Nirmal S., Keith M. Wille, Scott C. Bellot, and Enrique Diaz-Guzman. “Modern Use of Extracorporeal Life Support in Pregnancy and Postpartum.” ASAIO Journal 61, no. 1 (February 2015): 110–114.  CardioNerds Case Reports: Recruitment Edition Series Production Team Bibin Varghese, MD Rick Ferraro, MD Tommy Das, MD Eunice Dugan, MD Evelyn Song, MD Colin Blumenthal, MD Karan Desai, MD Amit Goyal, MD Daniel Ambinder, MD

CardioNerds (Amit Goyal & Daniel Ambinder) join Cedars-Sinai cardiology fellows (Natasha Cuk, Ronit Zadikany, Neal Yuan) for some drinks at the local pub 3rd Stop after a walk down Hollywood boulevard! They discuss a fascinating case of a massive pulmonary embolus presenting as STEMI. Dr. Babak Azarbal provides the E-CPR and program director Dr. Joshua Goldhaber provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Bibin Varghese with mentorship from University of Maryland cardiology fellow Karan Desai.    Jump to: Patient summary – Case figures & media – Case teaching – References – Production team Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his mid-40s with no known past medical history presented to the ER in PEA arrest with ongoing cardiopulmonary resuscitation (CPR). Prior to his arrest, his coworkers reported that he was complaining of lightheadedness, dizziness and that he was found slumped over at his desk. His EKG in the ambulance showed STE in aVR and V1 – V4 with TWI in III and aVF initially concerning for an anterior STEMI. He was cannulated with VA-ECMO for extracorporeal cardiopulmonary resuscitation (E-CPR) and was taken to the catheterization lab emergently. In the catheterization lab, his coronary angiogram did not show obstructive coronary disease. The interventionalists decided to perform a pulmonary artery (PA) angiogram which revealed a large amount of thrombus bilaterally in the proximal PAs. He underwent surgical embolectomy with removal of almost all his clot burden. The patient was thereafter cooled for neurological protection. Unfortunately, the patient had a very poor neurological exam with lack of brainstem reflexes upon rewarming. There was loss of gray-white differentiation on CT, and EEG and evoked potential testing were consistent with severe anoxic brain injury. After discussions with the patient’s family, the patient was transitioned to comfort care and subsequently passed away peacefully.   Case Media Click to Enlarge Right Coronary Artery Left Coronary System – 1 Left Coronary System – 2 Left Pulmonary Artery Right Pulmonary Artery Episode Schematics & Teaching Click to enlarge! The CardioNerds 5! – 5 major takeaways from the #CNCR case The patient presented initially with STE in aVR as well as the septal and anterior leads. What is the differential for an ST elevation in lead aVR? STE in aVR with diffuse ST depression can be a potential finding of LM or LAD stenosis. However, there have been several studies that have shown that the combination of STE and multi-lead STD was not associated with complete occlusion of a culprit vessel. Thus, the differential for STE in aVR more commonly includes significant LM or LAD stenosis, severe three-vessel disease with diffuse sub-endocardial ischemia (e.g., CAD in the setting of sepsis, anemia, shock), as well as pulmonary embolism with right ventricular injury (see below)! Remember that lead aVR is opposite I, aVL, II and V5-6 and thus elevation in aVR may represent reciprocal changes of diffuse sub-endocardial ischemia. Furthermore, aVR doesn’t directly overlie myocardium but reflects electrical activity from the RV outflow tract and basal septum. Thus, in the context of an anterior STEMI, STE in aVR (> 1mm) strongly predicts LAD occlusion proximal to the first septal perforator, which supplies the basal septum. The patient was found to have non-obstructed coronaries and was ultimately diagnosed with a PE. Could we have suspected that from the initial EKG? What are the EKG changes that have been noted in patients with a PE? Generally, an EKG does not make the diagnosis of PE, as most findings have low sensitivity and specificity. Rather, an EKG can be helpful in evaluating other causes of a patient’s cardiopulmonary symptoms and provide supporting evidence of acute PE. The EKG findings in acute PE can be thought to be secondary to three primary mechanisms: (1) increased adrenergic drive, (2) RV and/or RA dilation, and/or (3) RV myocardial ischemia and injury. The most common EKG fining is sinus tachycardia. Atrial arrhythmia (e.g., atrial fibrillation or flutter) can be seen and is predominantly a result of RA/RV dilation with increased adrenergic drive. Complete or incomplete RBBB may occur as the RBB is vulnerable to stretch, especially early in its course. Due to acute RV dilation with accompanying rotation of the heart in relation to the ECG leads (more commonly in sub-massive or massive PE), we can see right axis deviation, a dominant R-wave in V1, and the R to S transition point in the precordial leads shifting towards V5. As a result of ischemia and/or RV injury, we may see the classic S1Q3T3 pattern, but this is not a sensitive finding and thus its absence should not change decision-making. We can also see an RV strain pattern with T-wave inversions (TWI) in the right precordial leads (V1-V3) as well as the inferior leads. Non-specific ST-T changes are relatively common and along with sinus tachycardia, may be the most frequent finding. ST elevation in aVR with accompanying elevation in V1-V3 may be seen in PE (especially if complicated by obstructive shock). The injury current in the limb leads is directed towards aVR in this circumstance. In the precordial leads the injury current is more variable. A differentiating point between proximal LAD or LM acute MI and acute PE could be the presence of prominent reciprocal STD and the distribution of TWI. This patient presented in cardiac arrest and obstructive shock from a massive PE. What is the treatment for patients with a massive PE and cardiac arrest? In patients with cardiac arrest or circulatory collapse, VA-ECMO in combination with surgical embolectomy or catheter-directed treatment is given a Class IIb recommendation in patients with massive PE per 2019 ESC guidelines. In general, the decision to proceed with active thrombus removal, whether it be with thrombolytic-based, catheter-based, or surgical embolectomy, is driven by first the severity of the PE and secondarily by patient-specific factors for bleeding and co-morbidities. However, if VA-ECMO is pursued, it should not be a stand-alone strategy In patients with massive (AHA) or high risk (ESC) PE – defined as systolic blood pressure < 90 mmHg, the use of vasopressor medication or a drop in SBP > 40 mmHg for at least 15 minutes – systemic thrombolytic therapy carries a Class IB recommendation. Trial data has demonstrated earlier hemodynamic improvement with systemic thrombolysis compared to anticoagulation alone, especially if treatment is initiated within 48 hours of symptom onset Catheter directed therapy may have a role in massive PE – whether it be through mechanical, saline or ultrasound lysis – in patients who have persistent hemodynamic instability despite systemic thrombolysis and patients with moderate to high bleeding risk. Embolectomy is indicated in hemodynamically unstable patients with massive PE in whom thrombolytic therapy is contraindicated or patients who fail thrombolytic therapy. Furthermore, it may be considered early in patients with extensive clot burden where there is surgical expertise. Although the patient presented with refractory cardiac arrest, he was able to be stabilized with E-CPR before diagnostic evaluation was performed. What does ECPR stand for? Has it been proven to improve clinical outcomes? As defined by the AHA guidelines, extracorporeal cardiopulmonary resuscitation or ECPR is the use of VA-ECMO during the resuscitation of a patient in cardiac arrest, with the goal of providing end-organ perfusion while reversible causes of arrest are identified and treated. There have been several studies regarding the use of ECPR in out of hospital and in hospital cardiac arrest (OHCA and IHCA), respectively. It remains unclear whether ECPR is of consistent benefit with regards to morbidity and mortality as studies have lacked a uniform definition of EPCR, consisten inclusion criteria for ECPR, and many studies have been single-center introducing the potential for bias. Thus, in the 2019 AHA Focused Updated on ACLS guidelines, ECPR is given a Class 2b indication (with level of evidence C-LD), where it can be considered in select patients as rescue therapy when conventional CPR efforts are failing in clinical settings in which it can be quickly implemented and supported by trained providers. It sounds like the benefits of E-CPR remain to be further elucidated. Are there any specific features that help predict who would benefit from ECPR?   While we do not have high quality randomized data, observational data in EPCR has shown that shorter no flow times (i.e., CPR initiated within 5 minutes of arrest), total duration of CPR <60 minutes, intermittent return of spontaneous circulation, an initial shockable rhythm, and lower serum lactate concentration have been associated with increased survival with better neurologic recovery.  A well-known protocol is the University of Minnesota ECPR protocol (transport with ongoing CPR to the cardiac catheterization laboratory for ECPR) for patients with refractory VT/VF arrest. The inclusion and exclusion criteria for this protocol included  Inclusion: (1) OHCA with presumed cardiac etiology cardiac arrest; (2) first presenting rhythm is shockable (VF or VT); (3) Age 18 to 75 years; (4) Received at least 3 direct current (DC) shocks without sustained ROSC; (5) received Amiodarone 300 mg; (6) Body can accommodate a Lund University Cardiac Arrest System (LUCA) automated CPR device; and (7) Transfer time from the scene to the Cardiac Catheterization Lab of < 30 minutes  Exclusion: (1) ROSC before 3 shocks were delivered; (2) Nursing home residents: (3) DNR/DNI orders; (4) known terminal illness (e.g., malignancy); (5) Traumatic arrest; (6) PEA or asystole; (7) significant bleeding; (8) manual CPR as the only option  Using this strict UMN-ECPR protocol, Bartos et al. retrospectively compared 160 consecutive adult patients with refractory VT/VF arrest treated with ECPR to 654 patients treated with conventional CPR from the amiodarone arm of the ALPS study (Amiodarone, Lidocaine or Placebo study). They found ECPR had favorable survival compared with conventional CPR at each CPR duration interval <60 minutes; however, longer CPR duration was associated with worsening neurologic outcomes and survival in both groups. There remains considerable evidence gaps to define which patient populations would most benefit from this intensive resource.   References 2019 ESC Guidelines for Acute Pulmonary Embolism. American College of Cardiology  Konstantinides, S. V. et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur. Respir. J. 54, (2019).  Paul, J. D. & Cifu, A. S. Management of Acute Pulmonary Embolism. JAMA 324, 597–598 (2020).  Harhash, A. A. et al. aVR ST Segment Elevation: Acute STEMI or Not? Incidence of an Acute Coronary Occlusion. Am. J. Med. 132, 622–630 (2019).  Panchal Ashish R. et al. 2019 American Heart Association Focused Update on Advanced Cardiovascular Life Support: Use of Advanced Airways, Vasopressors, and Extracorporeal Cardiopulmonary Resuscitation During Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 140, e881–e894 (2019).  Yannopoulos Demetris et al. Minnesota Resuscitation Consortium’s Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out‐of‐Hospital Refractory Ventricular Fibrillation. J. Am. Heart Assoc. 5, e003732.  Rao Prashant, Khalpey Zain, Smith Richard, Burkhoff Daniel & Kociol Robb D. Venoarterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock and Cardiac Arrest. Circ. 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