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"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 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.

Advanced heart failure (HF) -- Stage D by American Heart Association/American College of Cardiology (AHA/ACC) criteria -- accounts for up to 10% of heart failure cases. That number is expected to along with the rising overall prevalence of HF and improving survival rates.

This stage, the final stage of the illness for many patients, is defined by symptoms that remain severe despite maximal guideline-directed medical therapy and device treatments, so a careful look at whether those modalities really are optimized is warranted. The stage is also characterized by the need for advanced treatments, which require referral to specialty care.

When advanced therapies are consistent with the patient's goals of care, timely referral is strongly recommended by the 2022 . This may help patients qualify for advanced therapies that aren't an option once end-organ dysfunction or cardiogenic shock develops. There's no need to wait for complete assessment, which is often done during the evaluation for advanced therapies.

High-risk features that might trigger consultation for advanced HF specialty assessment are found in several mnemonics:

• "" is helpful overall, but is most applicable to heart failure with reduced ejection fraction (HFrEF), as one "E" stands for EF of 35% or less

• and are more tailored to HF with preserved EF (HFpEF)

Annual review by an HF specialist also allows discussion of "current and potential therapies for both anticipated and unanticipated events, possible HF disease trajectory and prognosis, patient preferences, and advanced care planning," according to the for heart failure.

In advanced HF, treatment strategies are divided along lines of "destination" therapies and "bridges" to support patients to reach those destinations or, in some cases, to achieve some recovery of heart function.

Inotropes

For HFrEF patients, one of those bridges is continuous IV inotrope support, deemed by the AHA/ACC guidelines as reasonable for patients eligible for and awaiting mechanical circulatory support (MCS) or cardiac transplantation or to ease symptoms and functional status when patients aren't eligible for those "destination" therapies.

Other than those cases, the guidelines warn against long-term use of either continuous or intermittent intravenous inotropic agents. Such use risks arrhythmia and catheter-related infections and is associated with increased risk of death, likely via the arrhythmogenic properties of dobutamine and milrinone.

No single IV inotrope has emerged as a clear winner for better outcomes. An suggested choosing with consideration that phosphodiesterase inhibitors, investigational levosimendan, and low-dose dobutamine are vasodilators.

The consensus panel did note some advantages to levosimendan, based on a finding of reduced mortality in one and fewer rehospitalizations in . Although the trials forming this evidence base have been underpowered, the 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.

For all the inotropic agents, lower doses are preferred to minimize adverse effects. The guidelines note that longer periods of support might require a change in inotrope. In addition, "the ongoing need for inotropic support and the possibility of discontinuation should be regularly assessed."

Destination therapy for advanced HF patients generally centers on mechanical support and heart transplantation.

Mechanical Support

Durable MCS to support a heart no longer able to provide sufficient end-organ blood circulation can improve functional status, quality of life, and survival. MCS use is typically divided into two categories depending on the goal of care, either as a bridge to keep the patient alive and healthy enough to await a donor heart becoming available, or, , as the "destination" for patients who are not likely candidates for transplantation.

With newer-generation devices, 2-year survival approaches that of cardiac transplantation. The Interagency Registry for Mechanically Assisted Circulatory Support () data showed survival rates of 83.0% at 1 year and 51.9% at 5 years with durable MCS.

The AHA/ACC guidelines give their strongest endorsement of durable left ventricular assist device (LVAD) use in advanced HF with HFrEF with New York Heart Association (NYHA) class IV symptoms when patients are deemed dependent on continuous IV inotropes or temporary MCS.

LVADs also have a recommendation as "reasonable" for selected other patients with advanced HFrEF with NYHA class IV symptoms. "There is no clear 1-risk model to assess patient risk for complications, but factors such as elevated central venous pressure, pulmonary hypertension, and coagulopathy have been linked to poorer outcomes," the guidelines note.

Temporary support from percutaneous or extracorporeal VADs is also reasonable for patients with advanced HFrEF with hemodynamic compromise and shock either as a "bridge to recovery" or "bridge to decision" on implanting a durable device or seeking heart transplant, the guidelines state.

Discussion of temporary MCS -- and durable devices as well -- should be frank about the eventual need to turn off or explant the device, whether due to transplantation or recovery or even the desire to no longer prolong life after a catastrophic neurologic event or terminal cancer. In the , just 26.5% of MCS patients alive at 5 years post-implant had gotten a new heart and 30.8% remained on an MCS, while only a small fraction had explant due to myocardial recovery.

Heart Transplantation

After exhausting optimization of guideline-directed medical and device therapy and surgical options for stage D HF patients, cardiac transplantation may be the next step for patients eligible for it.

Transplantation has a class I indication for such patients, as it is linked to improved survival and quality of life in observational cohort data. "Good outcomes can be achieved in patients not only with HF that is primarily cardiovascular in origin, including reversible pulmonary hypertension, congenital heart disease, and hypertrophic cardiomyopathy, but also in patients with systemic conditions complicated by HF, such as muscular dystrophy, sarcoidosis, and amyloidosis," the guidelines note. The exception is amyloid light chain amyloidosis, which carries a high risk of recurrence in the donor heart.

While LVADs regardless of implant strategy have a that becomes greater than the likelihood of survival after around 4 to 5 years, adult heart transplantation is associated with median survival greater than 12 years. Median survival is less than 2 years in stage D HF without such advanced therapies.

In determining patient selection for advanced therapies like transplantation, patient selection review by a multidisciplinary team can help, typically pooling the skills of an HF cardiologist, surgeon, social worker, nurse, pharmacist, dietitian, and palliative medicine specialist.

Cardiopulmonary exercise testing and pulmonary artery catheterization can refine candidate prognosis and selection. The decision also must take into account comorbidity burden, caretaker status, and goals of care along with listing criteria from the International Society for Heart and Lung Transplantation.

Read previous installments of this series:

Part 1: Heart Failure: A Look at Low Ejection Fraction

Part 2: Exploring Heart Failure With Preserved Ejection Fraction

Part 3: Heart Failure With Reduced Ejection Fraction: Diagnosis and Evaluation

Part 4: Case Study: Lightheadedness, Fatigue in Man With Hypertension

Part 5: Heart Failure With Preserved Ejection Fraction: Diagnosis and Evaluation

Part 6: Medical Managment of Heart Failure

Part 7: Managing Heart Failure Comorbidities

Part 8: Case Study: Heart Failure Exacerbation Due to an Often Overlooked Cause

Part 9: Device-Based Therapies for Heart Failure

Part 10: Managing Heart Failure Hospitalizations