CardioNerds kicks off its advanced therapies series with Chair of the CardioNerds Heart Failure Council, Dr. Jenna Skowronski, co-chair of the series, Dr. Shazli Khan, and Episode FIT lead, Dr. Jason Feinman. In this first episode, they discuss the process of advanced therapies evaluation with Dr. Michelle Kittleson, Professor of Medicine and Director of Education in Heart Failure and Transplantation at Cedars-Sinai. In this case-based discussion, they cover the signs and symptoms of end-stage heart failure, the initial management strategies, and the diagnostic workup required when considering advanced therapies. Importantly, they discuss the special considerations for pursuing left-ventricular assist device (LVAD) versus heart transplantation as well as the multidisciplinary, team-based approach needed when advanced therapies are indicated.

Notes were drafted by Dr. Shazli Khan. Audio editing for this episode was performed by CardioNerds Intern, Julia Marques Fernandes.

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Pearls

Guideline-directed medical therapy (GDMT) is indicated in all heart failure patients and improves survival, but progressive symptoms and intolerance to GDMT can be warning signs of disease progression. The I-NEED-HELP mnemonic is an excellent reference when considering referral for advanced therapies (Figure).

Management of acute decompensation includes diuretics and possible inotropic support. The inotropic agent used should be whichever best suits your specific patient. Milrinone may result in more hypotension, whereas dobutamine may result in more tachycardia. Tachycardic and normotensive patients may do better with milrinone, while hypotensive patients with normal heart rates may do better with dobutamine. Notably, DoReMi found no difference between milrinone and dobutamine for patients with cardiogenic shock.

The initial diagnostic evaluation includes an echocardiogram, right heart catheterization (RHC), and often cardiopulmonary exercise testing (CPET) to objectively assess the status of the heart. Comprehensive labs, imaging and cancer screening are also needed to assess all other organs.

When making the decision to pursue advanced therapies, always ask:

Is the heart sick enough?

Is the rest of the body well enough?

These two questions provide a framework to guide if patients are optimal candidates for transplant versus LVAD.

The advanced therapies evaluation is a team sport! Patients will meet not only with advanced heart failure cardiologists, but also cardiac surgeons, psychiatrists, social workers, nutritionists and pharmacists. All team members are of critical value in the process.

Notes

1.) What are the key features of advanced cardiomyopathy, and when should providers consider referral for advanced therapies?

Advanced cardiomyopathy may present as recurrent hospitalizations for decompensated heart failure, intolerance to GDMT with symptomatic orthostasis and hypotension, and progressive symptoms of heart failure despite medical therapy.

The I-NEED-HELP mnemonic is a helpful tool to identify patients at risk of heart failure and is defined as follows: Need for Inotropic support, New York Heart Association (NYHA) Class IV symptoms, End-Organ Dysfunction, Ejection fraction <20%, Defibrillator shocks for ventricular arrhythmias, Recurrent HF hospitalizations, Escalating diuretic dose, Low blood pressure and Progressive intolerance of GDMT. See the Figure designed by Dr. Gurleen Kaur.

When patients demonstrate any of the above warning signs, they should be referred to advanced heart failure specialists for consideration of advanced therapies.

2.) What diagnostic testing is pursued when working up patients for advanced therapies? How does this workup differ whether you are in the inpatient or outpatient setting?

Work-up generally answers two key questions: is the heart sick enough and is the rest of the body well enough?

Workup includes an echocardiogram that may show specific features concerning for end-stage heart failure (EF <20%, dilated and remodeled left ventricle, reduced right ventricular function, etc.).

A RHC provides information on the filling pressures of the heart for management in the acute setting, but also helps give an objective measure of the cardiac output to assess how sick the heart is. Importantly the RHC also provides key information on the presence of pulmonary hypertension.

Obtaining a comprehensive metabolic panel provides valuable information on end-organ dysfunction, as kidney or liver abnormalities are suggestive of worsening disease.

Outpatients presenting for referral may also undergo CPET as an objective confirmation of decreased functional capacity. Typically, a peak VO2 max of <14 mL/kg/min is indicative of advanced disease.

CT imaging, as well as other cancer screening tools, may be employed to ensure there is no systemic disease that would prohibit advanced therapies.

3.) Who makes up the multidisciplinary advanced therapies team?

The ACC/AHA/HFSA 2022 guidelines for heart failure support using a multidisciplinary team approach in managing HF. This collaborative care model has been shown to reduce hospital admissions and healthcare expenses while enhancing patient adherence to self-care practices and recommended medical treatments.

The multidisciplinary team consists of cardiologists, cardiac surgeons, advanced practice providers, psychiatrists, pharmacists, social workers, nutritionists, and other specialists.

4.) What are the medical factors to consider when deciding between transplant versus LVAD, and what social determinants of health play a role?

The medical evaluation and workup done during the advanced therapies evaluation help answer two crucial questions: Is the heart sick enough? Is the rest of the body well enough? All patients should be assessed for extracardiac disease that may impact survival after advanced therapies.

While selection between transplant versus LVAD varies by program and institution, general principles considered include the allocation system and regional wait times, patient’s age, and extracardiac comorbidities.

Generally, patients being considered for heart transplantation should be devoid of conditions that have a five-year survival of <70% or a ten-year survival of <50%. This is also because patients undergoing organ transplantation require immunosuppressive medications, which may further exacerbate their other systemic conditions.

Social support and internal motivation also play a role, as it is important for patients to attend multiple follow-up appointments and maintain strict adherence to their immunosuppressive medications.

Graphic – Stage D (Advanced) Heart Failure

Designed by Dr. Gurleen Kaur

References

Morris AA, Khazanie P, Drazner MH, et al; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Hypertension. Guidance for timely and appropriate referral of patients with advanced heart failure: a scientific statement from the American Heart Association. Circulation. 2021;144(15):e238-e250. doi:10.1161/CIR.0000000000001016 https://www.ahajournals.org/doi/10.1161/CIR.0000000000001016
Truby LK, Rogers JG. Advanced heart failure: epidemiology, diagnosis, and therapeutic approaches. JACC Heart Fail. 2020;8(7):523-536. doi:10.1016/j.jchf.2020.01.014 https://www.sciencedirect.com/science/article/pii/S2213177920302080?via%3Dihub
Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, et al; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063 https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063
Guglin M, Zucker MJ, Borlaug BA, Breen E, Cleveland J, Johnson MR, Panjrath GS, et al; ACC Heart Failure and Transplant Member Section and Leadership Council. Evaluation for heart transplantation and LVAD implantation: JACC Council perspectives. J Am Coll Cardiol. 2020;75(12):1471-1487. doi:10.1016/j.jacc.2020.01.034 https://www.sciencedirect.com/science/article/pii/S0735109720304150?via%3Dihub

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