Expanding Therapies and Challenges in Heart Failure Management in 2024

Advances in ATTR-CM Treatments

• The HELIOS-B trial showed that vutrisiran (Amvuttra; Alnylam), a novel “silencer” agent for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), reduced all-cause mortality and recurrent cardiovascular events compared to placebo.
• The benefits of vutrisiran were evident in both the overall population and among patients not on background tafamidis (Vyndaqel and Vyndamax; Pfizer), the first FDA-approved drug for ATTR-CM.
• The FDA  approved acoramidis (Attruby; BridgeBio) for ATTR-CM, based on the ATTRibute-CM trial, marking the second approved therapy for this condition.

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Cardiac Myosin Inhibitors for HCM

• The SEQUOIA-HCM trial demonstrated that aficamten (Cytokinetics) improved peak oxygen uptake and other health indicators in patients with obstructive hypertrophic cardiomyopathy (HCM).
• Updated guidelines from the AHA and ACC highlighted advancements in therapies, including mavacamten (Camzyos; Bristol Myers Squibb), approved in 2022 for symptomatic obstructive HCM.

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Concerning Trends in HF Mortality

• A study published in April suggested that heart failure (HF) mortality rates have increased, potentially reversing years of progress, with current rates higher than in 1999.
• Experts debated whether these trends reflect genuine changes or issues related to the classification and coding of causes of death.

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FINEARTS-HF Trial and MRAs

• The FINEARTS-HF trial showed that finerenone (Kerendia; Bayer AG), a nonsteroidal mineralocorticoid receptor antagonist (MRA), reduced worsening HF events and cardiovascular mortality in patients with HFmrEF or HFpEF.
• MRAs continue to be a cornerstone of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), although their uptake remains suboptimal.

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GLP-1 Receptor Agonists in HFpEF

• The STEP-HFpEF DM trial demonstrated that semaglutide (Wegovy; Novo Nordisk) improved symptoms and physical function in patients with obesity-related HFpEF and type 2 diabetes.
• The SUMMIT trial revealed that tirzepatide (Zepbound; Eli Lilly) significantly reduced cardiovascular mortality and worsening HF events in patients with HFpEF and obesity.
• Challenges with long-term adherence due to high costs and side effects remain significant barriers to the broader use of these therapies.

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Implications of ADHD Medications and ARNI Therapy

• A study linked ADHD medications to cardiomyopathy in young adults, raising concerns about their cardiovascular risks.
• The SARAH trial found that sacubitril/valsartan (Entresto; Novartis) helped protect against cardiotoxicity from anthracycline chemotherapy in high-risk cancer patients.

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RELIEVE-HF Trial: Ventura Interatrial Shunt

• The RELIEVE-HF trial found that the Ventura interatrial shunt (V-Wave), though safe, did not improve prognosis or symptoms across a range of HF patients.
• Potential benefits were observed in HFrEF patients, but harm was suggested in those with HFpEF, highlighting the need for careful patient selection.

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Sharp Increases in HF Incidence

• The Heart Failure Society of America (HFSA) reported significant increases in HF incidence among younger populations, racial/ethnic minorities, and individuals with comorbid conditions.
• The HFSA issued a "call to action" to address these disparities and the growing burden of HF in the US population.

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Summary of Challenges and Opportunities in HF Care

• Despite worrisome trends, the HF community now offers more treatment options than ever, with challenges shifting to optimizing combinations and sequences of therapies.
• Experts noted the dramatic transformation in the HF landscape over the past two decades, with optimism for continued progress in the coming years.