Managing Advanced Cardiomyopathy

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

For many patients with cardiomyopathy, advanced heart failure (HF) is the final stage of the illness. Advanced HF accounts for up to 10% of heart failure cases, with prevalence expected to rise due to the growing overall HF population and improving survival.

After progression of their disease, patients enter Stage D HF by the American Heart Association/American College of Cardiology (ACC) classification when symptoms remain severe despite maximal guideline-directed medical and device treatments, thus requiring specialized interventions.

That requires a careful look to see if all therapies likely to improve clinical status really have been optimized, although the LIFE trial showed that sacubitril/valsartan (Entresto) wasn't any better than an angiotensin receptor blocker alone in advanced HF and actually tended to worsen HF hospitalization risk. Assessing whether any coexisting pulmonary illnesses might be behind the patient's dyspnea is also worthwhile, according to HF guidelines.

Referral to specialty care for advanced HF shouldn't wait for complete assessment -- which likely will be done when evaluating these patients for advanced therapies -- but should be timely, since patients may no longer qualify after developing end-organ dysfunction or cardiogenic shock. Timely referral has a class I recommendation in guidelines, when consistent with the patient's goals of care.

One well-known mnemonic for when to refer patients for advanced HF consultation is "I NEED HELP."

• I: Intravenous inotropes

• N: New York Heart Association (NYHA) class IIIB to IV or persistently elevated natriuretic peptides

• E: End-organ dysfunction

• E: Ejection fraction of 35% or less

• D: Defibrillator shocks

• H: Hospitalization more than once in 12 months

• E: Edema despite escalating diuretics

• L: Low systolic blood pressure (90 mm Hg or less), high heart rate

• P: Prognostic medication or progressive intolerance or down-titration of medication

Annual review by a specialist for established advanced HF patients provided an opportunity to "discuss current and potential therapies for both anticipated and unanticipated events, possible HF disease trajectory and prognosis, patient preferences, and advanced care planning," notes the ACC Expert Consensus Decision Pathway for heart failure.

Inotropes

HF guidelines deem continuous IV inotropes reasonable as "bridge therapy" for patients eligible for and awaiting mechanical circulatory support or cardiac transplantation or as palliation of symptoms and functional status in patients who aren't eligible for either of those "destination" therapies.

However, outside of those two use cases, the guidelines warn that long-term use of either continuous or intermittent intravenous inotropic agents is potentially harmful. Such use carries a risk of arrhythmias and catheter-related infections.

Patients with an implantable cardioverter-defibrillator (ICD) are at lower risk of dying from such arrhythmias, with a relatively low risk of inappropriate shocks for sinus tachycardia, which may be further lowered with use of beta-blockers. For other patients without an ICD or who chose to have their ICD deactivated for palliative reasons, the arrhythmia risk should be discussed with patients. "Patients may elect to have their shocking devices deactivated, especially if they receive numerous shocks," the guidelines note.

As to the choice of inotrope, the evidence hasn't suggested a clear winner. The choice should take into consideration that norepinephrine, epinephrine, and high-dose dopamine are vasoconstrictors, whereas phosphodiesterase inhibitors, levosimendan, and low-dose dobutamine are vasodilators, according to one expert consensus group. That group suggested some advantages to levosimendan based on a finding of reduced mortality in one meta-analysis and fewer rehospitalizations in another, looking across the available underpowered trials.

The 264-patient LeoDOR trial is underway to test levosimendan against placebo in advanced chronic HF for combined death, urgent heart transplantation or ventricular assist device placement, or non-fatal HF events.

Whatever agent is selected, guidelines suggest that lower doses are preferred to minimize adverse effects and that longer periods of support might necessitate changing the inotropic agent. "Similarly, the ongoing need for inotropic support and the possibility of discontinuation should be regularly assessed," the recommendations note.

Mechanical Support

Durable mechanical circulatory support (MCS) is deemed most appropriate for advanced heart failure with reduced ejection fraction (HFrEF) and a dilated ventricle. Left ventricular support devices (LVADs) have a class Ia recommendation for HFrEF and NYHA class IV symptoms dependent on continuous IV inotropic agents or temporary mechanical circulatory support.

Durable devices can be reasonable in other advanced HFrEF with NYHA class IV symptoms patients as well, according to the guidelines.

Either way, MCS can improve functional status and quality of life and prolong survival. Outcomes have improved with newer-generation devices such that the 2-year survival approaches that of cardiac transplantation. In 2020 INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) data, 2-year survival rates were 78.3% for patients using an LVAD as a bridge to transplant and 70.6% for those getting an LVAD as their "destination" therapy.

Temporary MCS, whether percutaneous or extracorporeal, is also deemed reasonable for patients with advanced HFrEF with hemodynamic compromise and shock either as a "bridge to recovery" or "bridge to decision" about a durable device or transplantation.

While hypertrophic cardiomyopathy (HCM) traditionally rendered patients ineligible for LVADs due to small LV cavities and relatively preserved EF, the 2020 HCM guidelines noted that case series have demonstrated "acceptable outcomes" in these patients receiving continuous flow LVADs, with better post-LVAD survival in patients with LV cavities larger than 46-50 mm.

Pulmonary artery catheterization can help select candidates for MCS or other advanced therapies, including transplant. Patient selection review can help too, involving a multidisciplinary team typically comprising an HF cardiologist, surgeon, social worker, nurse, pharmacist, dietitian, and a palliative medicine specialist.

A frank discussion is needed with patients before discussing any form of MCS, but especially temporary devices, to make clear that the device will eventually be turned off or explanted, whether due to transplantation or recovery or even in cases where the MCS would prolong life when not desired because of a catastrophic neurologic event or terminal cancer.

Surgery and Transplantation

For cardiomyopathy patients with advanced HF, heart transplantation has a class I indication. Median survival after transplant has reached more than 12 years, whereas it's less than 2 years in stage D HF without such advanced therapies. Functional status and health-related quality of life also benefit.

Transplantation is recommended due to good outcomes even in hypertrophic cardiomyopathy, sarcoidosis, and amyloidosis, although not the subset of amyloid light chain (AL) amyloidosis. In AL amyloidosis, there is a high risk of recurrence in the transplanted heart and progressive amyloid deposition in other organs hurts survival as well, which is only 20-30% at 5 years post-transplant.

"Sarcoidosis can occasionally recur in the transplanted heart as early as 24 weeks after transplantation; however, these recurrences usually respond to treatment with steroids," the HCM guidelines note, calling for consideration of transplantation in HCM with intractable arrhythmias as well. "Other surgical interventions have been reported with variable success in cardiac sarcoidosis, such as aneurysm resection and ventricular exclusion of affected myocardium."

Cardiopulmonary exercise testing can refine candidate prognosis and selection, taking into account comorbidity burden, caretaker status, and goals of care along with listing criteria from the International Society for Heart and Lung Transplantation.

Palliative Care

Fatigue, dyspnea, pain, and depression diminish quality of life for advanced HF patients, which palliative care can help address. However, such supportive care is widely acknowledged as underutilized.

A large analysis of community and academic hospitals showed that compared with cancer patients, patients with advanced HF had palliative care initiated later during hospitalization, at a lower Palliative Performance Scale score, and more often while in critical care. The consultations were primarily to discuss care planning.

Palliative care should not be equated with hospice care. Rather than just focusing on end-of-life care when curative treatments are no longer warranted, palliative care can include pursuing aggressive treatments and curative therapies, such as heart transplantation.

In advanced HF, the use of palliative care is less dependent on prognosis than in cancer, for example. Disease course is much less predictable, with temporary improvement with aggressive diuresis and optimization of medical management often followed by worsening symptoms that lead to readmission in advanced stages.

Getting the palliative care team involved early not only helps with symptom management but also ensures timely transition to hospice for patients who are not candidates for cardiac transplant.

The ACC Expert Consensus Decision Pathway for HF called for at least annual preparedness planning discussions with patients that cover "clinical status and current therapies, estimates of prognosis, clarification of patient values and beliefs, anticipation of treatment decisions, and advanced care directives that identify surrogate decision-makers."

For the nonspecialists who provide most of the palliative care currently, the ACC consensus group suggested focusing on quality of life, especially as the disease progresses, and maintaining meticulous management of HF therapies -- particularly diuretics -- to control symptoms through end of life.

However, some recommended therapies may be discontinued as patients transition through a phase focused on quality survival into comfort-only care or hospice, which may include reducing neurohormonal antagonists in the setting of symptomatic hypotension and deactivating defibrillator therapy.

"Decision support tools (patient decision aids) help frame options, which should then be followed by dynamic and personalized conversations," the ACC group added, pointing to patient education resources from the Heart Failure Society of America.

Read previous installments in this series:

Part 1: Cardiomyopathy: What are the Signs, What are the Symptoms?

Part 2: Diagnosing Cardiomyopathy: History, Examination, and Testing

Part 3: Cardiomyopathy: Epidemiology, Etiology, and Pathophysiology

Part 4: Case Study: Cardiomyopathy From Epinephrine in Anesthesia

Part 5: Cardiomyopathy: Cascade Screening for Families

Part 6: Cardiomyopathy: Outside the Office

Part 7: Deciding on Implantable Cardiac Devices for Cardiomyopathy

Part 8: Case Study: The Dangerous Habit That Led to Non-Ischemic Cardiomyopathy in a Healthy Man

Part 9: What to Know About Medical Therapy for Cardiomyopathy

Part 10: Inpatient Management of Cardiomyopathy

Part 11: Addressing Comorbidities in Cardiomyopathy