After years of toil by their field, Penn Medicine physicians focused on pumping challenges with the heart have a cautiously hopeful message to share.
First, they note that it’s not time to declare heart “failure” a misnomer, as much work remains. An estimated 6.2 million people live with the disease in the U.S., a number expected to rise to 8 million by 2030. The disease currently causes 900,000 hospitalizations each year, and a quarter of patients still die within a year of diagnosis.
At the same time, though, heart failure no longer has to mean a steady and inexorable decline in health. With new medications and improved devices, care teams can go beyond slowing progression and stabilize the heart for extended periods. They can keep patients out of the hospital, extend survival and support quality of life. For a number of patients, ventricular function even improves — an unprecedented achievement.
The advances cover a broad range of heart failure etiologies, in some cases offering effective treatment options for the first time. They frequently represent a radical shift in approach, as reflected by the major guidelines update released earlier this year.
“These therapies have changed the natural history of heart failure,” says Lee Goldberg, MD, section chief of Advanced Heart Failure and Cardiac Transplant at Penn Medicine. “We’ve really been able to bend the curve.”
To keep the momentum going, the Penn Heart Failure Program continues to participate in trials of promising therapies, with a focus on diverse participation. The team goes into neighborhoods for health checks and educational sessions, to address higher heart failure rates among people of color. And it’s seeking ways to further support community physicians. (It hosted a two-day “State-of-the-Art Heart Failure Course” for continuing medical education in October.)
The team is also taking a closer look at its inpatient and outpatient care, to achieve even better outcomes. It’s among a select group of programs working with the American Heart Association’s Implement-HF initiative to increase healthy life expectancy.
“We’re looking at our performance and trying to understand how are we doing, where are the gaps and what can we do better?” Goldberg says.
Updated Heart Failure Guidelines Capture the Promise of New Therapies
Published in April, the updated guidelines reflect evidence gathered by the American Heart Association, the American College of Cardiology and the Heart Failure Society of America. Penn Medicine contributed to many of the clinical trials driving the changes, and several Penn heart failure physicians helped write or review the revisions.
Heart Failure Staging and Risk
Among other updates, the guidelines provide strategies for prevention, risk stratification and prognosis, as well as for understanding patient trajectory. They embrace the use of biomarkers across the heart failure journey, from people at risk to those with chronic cases. And they call for frequent reassessment of left ventricular ejection fraction (LVEF).
The guidelines establish four stages of heart failure, to complement the existing New York Heart Association classification:
- Stage A (at risk): Risk factors include hypertension, cardiovascular disease, diabetes, obesity, cardiotoxic agents, family history and genetic variants.
- Stage B (pre-HF): In this stage, a patient has structural heart disease, shows signs of increased filling pressure, or has risk factors for heart failure and higher biomarkers.
- Stage C: A patient has heart failure and experiences symptoms, or did so previously.
- Stage D: Even with optimized medical therapy, a patient has symptoms that interfere with daily life and endures repeated hospitalizations.
New Approaches to Guideline-Directed Medical Therapy
Notably, guideline-directed medical therapy (GDMT) also shifted, reflecting significant clinical trial findings and a series of new drug approvals since 2015. To start, treatment of patients with LVEF of 40 percent or less (reduced ejection fraction) now calls for four kinds of medications aimed at heart failure.
Patients should still receive a beta blocker and mineralocorticoid receptor antagonist (MRA). In addition, an angiotensin receptor-neprilysin inhibitor (ARNi) is now the first choice for renin-angiotensin system inhibition (RASi), with other options such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB) or hydralazine and nitrates available when it’s not tolerated.
The fourth class, sodium-glucose cotransporter-2 (SGLT2) inhibitors, are repurposed medications that represent a new and effective option for a range of heart failure. Clinical trials have shown a clear impact on morbidity and mortality for reduced ejection fraction. Additional trials are underway to further confirm early evidence of benefit for mildly reduced ejection fraction (LVEF 41 to 49 percent) and preserved ejection fraction (above 49 percent).
“You can actually see turnaround,” says Hansie Mathelier, MD, attending heart failure cardiologist at Penn Presbyterian Medical Center. “That’s very exciting.”
Guidelines for Special Populations, Therapy Devices and Advanced Heart Failure
Other medical therapy advances include options for light chain and transthyretin cardiac amyloidosis. Some medications also gained approval after the guidelines, including vericiguat for patients who don’t respond to four-drug therapy and mavacamten for obstructive hypertrophic cardiomyopathy (HCM).
On the device side, Penn Medicine is investigating another type of cardiac resynchronization therapy and an alternative to CRT called cardiac contractility modulation (CCM). These options could support patients not eligible for standard therapy and help prevent disease progression.
If patients do develop advanced heart failure, an updated left ventricular assist device (LVAD), the HeartMate 3, gained approval in 2017. With longer survival and fewer complications, the newer model offers an improved option for both bridge and destination therapies. Transplant remains the gold standard, with Penn Medicine and other programs working to expand the donor pool and increase organ viability.
Importance of Heart Failure Specialty Care
The updated guidelines reemphasize the benefit of timely referral to a specialized program for patients progressing toward stage D and advanced heart failure. The heart failure team can then review medical therapy and assess further options.
Goldberg also sees a role for heart failure programs in supporting community physicians earlier in the course of disease, well before stage D. The four-medication regimen comes with new requirements and nuances, particularly for SGLT2 inhibitors. And additional medications should be considered for certain populations.
Heart failure can also cause complications such as functional mitral regurgitation, atrial fibrillation and pacing challenges, potentially requiring device placement or other surgery on top of medical therapy. Patients also often need exercise or diet plans, and many face barriers to care and treatment adherence. Up to 70 percent have a comorbidity — hypertension, diabetes, kidney disease, sleep apnea or chronic obstructive pulmonary disease — that adds complexity.
“Care has become more subspecialized and more complex,” Goldberg says. “It’s important that we’re seen as a resource and a collaborator.”
In addition to inpatient care, the Penn Heart Failure Program can see outpatients within seven days. It follows a “shared care” model, in which community partners perform standard procedures, conduct much of the follow-up imaging and bloodwork, and provide day-to-day management. Patients can come for a one-time consultation or evaluations at set intervals.
“For specialty centers, you need to have good outcomes and you need to have ongoing communication, coordination and care,” says Ross Zimmer, MD, director of the Heart Failure Program at Penn Presbyterian. “You create a roadmap to follow.”
How Penn Medicine Can Help Your Heart Failure Patients
The Heart Failure Program at Penn Medicine can assist with:
- Confirming an uncommon diagnosis and providing subsequent care: The program features more than 20 specialists certified by the American Board of Internal Medicine in Advanced Heart Failure and Transplant Cardiology. Subspeciality expertise extends to pulmonary hypertension, cardiac amyloidosis, cardiac sarcoidosis and inherited cardiovascular disease, including muscular dystrophies.
- Adjusting GDMT: Since the team was involved with clinical trials and guideline updates, it had medication protocols in place well before the April release. It has previous experience with SGLT2 inhibitors, as well as a team of pharmacists who can help with access.
- Treating complications: Penn Medicine cardiac surgeons, electrophysiologists and interventional cardiologists can perform more uncommon procedures and device placements, such as CCM implantation and ablations in the left ventricular apex. For functional regurgitation, physicians are exploring new options to repair or replace the mitral and tricuspid valves.
- Managing comorbidities and overcoming barriers to care: Patients have coordinated access to a wide range of specialties across Penn Medicine. The Heart Failure Program also features substantial infrastructure and capacity. Social workers and a nutritionist provide personalized attention. Certified heart failure nurse coordinators cover the depth of follow-up required. Collectively, the team also represents a diverse ethnic and racial makeup.
“We might be able to help engage a patient in a different way,” says Joyce Wald, DO, an attending heart failure cardiologist at the Hospital of the University of Pennsylvania and Medical Director of the Cardiogenic Shock Program. “Don’t hesitate to call with anything.”
To reach the Penn Heart Failure Program, please call 215-615-0800.
Timeline of Recent Heart Failure Advances
- 2015: The combination of sacubitril and valsartan — the only ARNi currently available — gains approval. The PARADIGM-HF trial showed the combination was superior to valsartan alone.
- 2017: The HeartMate 3 gains approval after the MOMENTUM 3 trial.
- 2019: Tafamidis meglumine and tafamidis gain approval for transthyretin-mediated amyloidosis (ATTR) after the ATTR-ACT trial.
- 2020: An SGLT2 inhibitor — dapagliflozin — gains approval for heart failure with reduced ejection fraction after the DAPA-HF trial.
- 2021:
- Daratumumab, given in combination with bortezomib, cyclophosphamide and dexamethasone, gains approval for newly diagnosed light chain amyloidosis (AL). It followed the ANDROMEDA trial.
- A second SGLT2 inhibitor, empagliflozin, gains approved for reduced ejection fraction after the EMPEROR-Reduced trial. It later gains approval for preserved ejection fraction following the EMPEROR-Preserved trial.
- Vericiguat gains approval for reduced ejection fraction after the VICTORIA trial.
- 2022: Mavacamten gains approval for obstructive hypertrophic cardiomyopathy after the EXPLORER-HCM trial.