Heart failure (HF) therapies have advanced rapidly in recent years, but challenges in workflow, site-based trial execution, and the implementation of findings appear to hinder ongoing HF optimization across populations. The reviews in this special collection highlight the progression of HF from the intensive care unit through the clinic and into the home.1–5
These manuscripts span five domains, including cardiogenic shock thresholds in restrictive physiology, device detection and congestion management, cardiometabolic therapies that are redefining long-term HF treatment, specific treatments for transthyretin amyloid cardiomyopathy (ATTR-CM), and health literacy as the limiting factor to effective use of HF treatments in the real world. The collection provides a coherent view of the various stages and presentations of HF that occur, along with the challenges ahead as we seek to implement ongoing new HF treatments (Figure 1 ). Although therapies continue to demonstrate efficacy in trials, ongoing implementation research will be required to optimize each therapy along an individual’s HF trajectory.
Cardiogenic Shock and Restrictive Cardiomyopathies: Advances at the Threshold of Heart Failure Care
The trigger for many advanced HF therapies usually occurs at the point of cardiogenic shock. Although only a small proportion of patients have stage D HF, millions live with HF in the US, while donor hearts remain limited.6,7 Additionally, there are a limited number of centers with left ventricular assist device experience or the capacity for high-volume mechanical circulatory support. As a result, cardiogenic shock still defines our ceiling in advanced HF.
The review by Abou Hassan and colleagues furthers our understanding of the complex differences between cardiogenic shock and restrictive physiology.1 The review documents the nature of managing a poorly filled ventricle, which is heavily reliant on preload. The use of inotropes and mechanical support also differs in restrictive physiology, which explains why restrictive shock differs from post-MI shock. The landscape of cardiogenic shock continues to broaden as evidence demonstrates venoarterial extracorporeal membrane oxygenation (VA-ECMO) can stabilize profound shock, yet it often needs unloading and careful right-sided management. The review provides a comprehensive view of the advances in cardiogenic shock management, which may further stabilize the highest risk HF patients who will ultimately require heart transplant or left ventricular assist device. The use of these measures in patients with a low likelihood of survival remains under investigation.
Managing Stage C Heart Failure Patients: Device to Decongestion Innovation
Benarroch and colleagues review the role of device therapy in the chronic management of Stage C HF patients.2 The therapies demonstrate the ability to detect earlier indicators of congestion and ultimately reduce HF hospitalizations. For instance, CardioMEMS, an implantable pulmonary artery sensor, reduced HF hospitalizations in the CHAMPION trial by 39% in the treatment arm. Again, although efficacy is clear from much of the randomized clinical trial data, the effectiveness of these interventions requires proper implementation and planning for escalation when triggered events occur. These tools still require a responsive team and a clear escalation plan.
Transcatheter mitral repair combined with guideline-directed medical therapy was associated with a significant reduction in both HF hospitalizations and mortality as compared to guideline-directed medical therapy alone in the COAPT trial.8 However, MITRA-FR did not reduce the composite of death from any cause or unplanned hospitalization for HF at 12 months, highlighting the importance of patient selection and trial design.9
With ongoing technological advancements, tricuspid interventions are evolving. The TRILUMINATE Pivotal demonstrated that tricuspid transcatheter edge-to-edge repair significantly reduced the severity of tricuspid regurgitation and improved quality of life.10 TRISCEND II demonstrated a significant improvement in a hierarchical composite endpoint at 1 year for transcatheter tricuspid valve replacement (win ratio = 2.02), driven by improvements in symptoms and health status; however, this was accompanied by an increased need for pacemakers and a higher bleeding risk.11 Ultimately, the ‘practical’ message regarding tricuspid interventions has remained consistent: demonstrated results suggest reduced congestion and improved patient experience, although it remains most successful when used in conjunction with a system that translates signals and anatomy into timely action.
Guideline-directed Medical Therapy Remains Central Heart Failure Therapy, but Systems Infrastructure is Paramount
Lopez and colleagues provide a comprehensive review of reviews of the evidence for SGLT-2 inhibitors and GLP-1RAs, given their longstanding use in conditions within the cardiac–kidney–metabolic paradigm.3 Results from the DAPA-HF trial were the first to demonstrate that dapagliflozin reduced worsening HF or cardiovascular death by 26%.12 Additionally, pertaining to HF with preserved function, EMPEROR-Preserved reported empagliflozin reduced the composite of cardiovascular death and first HF hospitalization by 21%, with similar trials conferring benefit in the higher ejection fraction (EF) ranges. Clinical inertia remains a challenge to optimize SGLT-2 inhibitor use in the population.
Recent evidence suggests that the story of optimal GLP-1RAs in the HF population remains to be told. For instance, agents such as semaglutide and tirzepatide have demonstrated significant improvements in obesity-related HF with preserved ejection fraction (HFpEF), with associated improvements in symptoms and quality-of-life measures. However, earlier trials of GLP-1RAs, such as liraglutide, did not yield similar benefits. Instead, there was a slight signal of safety concerns, with higher hospitalizations reported in the therapeutic arm. That said, the efficacy data are clear, as benefits exist for HFpEF treatments, although further investigations are necessary to evaluate other HF phenotypes.
A New Era of Heart Failure Management: Alignment of Phenotype and Genotypes
As our understanding of the human genome continues to expand, the therapeutic landscape for genetic cardiomyopathies is evolving rapidly.4 Clinical trials focusing on various mechanisms of ATTR-CM, particularly the variant Val142Ile, have led to the approval of several interventions to slow disease progression. Each class of newer therapies targets a different mechanism of action: stabilizers block amyloid tetramer dissociation, silencers reduce ATTR-CM protein production, and depleters increase the clearance of abnormal protein fibrils. Tafamidis improved outcomes in ATTR-CM, including lower all-cause mortality (HR 0.70) and fewer cardiovascular hospitalizations.13 Acoramidis improved a hierarchical composite endpoint in ATTRibute-CM (win ratio = 1.8).14 Vutrisiran reduced mortality and recurrent cardiovascular events in HELIOS-B (HR 0.72) and is now Food and Drug Administration (FDA)-approved for ATTR-CM.15 The therapeutic landscape now affords serious discussion of access to treatment and how to increase awareness of ATTR-CM in the community, particularly with a predominance of Val142Ile cases seen in Black or African Americans with a particular western African inheritance. Other investigations will ultimately determine whether the separate classes of medication can be used earlier upstream to manage ATTR-CM in selected individuals, providing the potential of longer survival rates overall.
The Missing Link for Real-world Heart Failure Outcomes: Communication and Health Literacy
The final review of this series by Latif and colleagues highlights persistent gaps in HF care in effective communication and health literacy assessment.5 In reality, the rules of health literacy assessment have not been static; they have become increasingly complex as newer HF therapies emerge. Although optimal implementation of HF therapies depends on a certain health-literate understanding, we must also assume accountability for the fact that, as the HF paradigm changes in scope and therapeutics, we face an ever-widening divide between the value of all therapies and the value of patients. The authors’ view emphasizes the need to align the pace of patient education with the rapid advancement of therapies and interventions. Although many patients have difficulty understanding their HF diagnosis, symptoms, and prognosis, the medication and therapeutic guidelines have become increasingly complex for non-HF clinicians. Thus, it stands to reason that if provider education has not kept pace with guideline-derived medical therapies, how can we expect patients to keep pace with the nuances of HF treatment?
In essence, health literacy shapes outcomes; the medical community bears significant accountability for helping the HF community understand the value of available therapies and the promise of future research. As technological innovations have provided greater conveniences in Western civilization, communication must begin on a multidimensional platform that enables understanding of the written word and other means of communication. Thus, technicalities of comprehension, such as readability and complexity, must be tailored to the populations of interest. Ultimately, adequate provider communication can enhance patients’ health literacy.
Efficacy Becomes Effectiveness Only When Communication Changes Behavior
Among the widespread discussions of several key aspects of HF management, a central theme has emerged: the continued growth of HF clinical trial activity, particularly in artificial intelligence and the global clinical trial market. However, these studies also link the sophisticated findings of clinical trials to FDA-approved therapies. Yet, without adequate investment in defining health literacy as we shift the goalposts with phenotypic and therapeutic nuances, we risk an even greater lag in population-level understanding of, or value placed on, therapeutic advances in HF. As a result, disseminating information and resources that combat misinformation and enhance health literacy and self-preservation measures are critically essential. The work to improve HF outcomes begins with understanding physiology that informs clinical interventions and culminates in language that promotes better HF care for all.