What are the current research gaps in heart failure (HF) and sickle cell disease (SCD)?

From the Guidelines

Current research gaps in heart failure (HF) and sickle cell disease (SCD) include the need for specialized treatment protocols that address the unique pathophysiology when these conditions coexist, with a particular emphasis on bridging the gap between evidence and care, as highlighted in a recent study 1. The lack of optimal heart failure medication dosing in sickle cell patients is a significant concern, as standard medications like ACE inhibitors, beta-blockers, and aldosterone antagonists have not been adequately studied in this population.

• Research is needed to investigate how chronic hemolysis and iron overload contribute to cardiac dysfunction in sickle cell disease, and whether chelation therapy with medications like deferasirox or deferoxamine might prevent heart failure development.
• The mechanisms of pulmonary hypertension in sickle cell patients and its relationship to left ventricular dysfunction require further investigation, as do the effects of hydroxyurea, the primary disease-modifying therapy for sickle cell disease, on cardiac outcomes.
• More research is needed on biomarkers that could predict heart failure development in sickle cell patients before clinical symptoms appear, as well as prospective studies examining the effectiveness of early cardiac screening protocols and investigations into whether exchange transfusion protocols might prevent heart failure progression, as discussed in a systematic review of clinical practice guidelines and recommendations for heart failure with preserved ejection fraction management 1. The development of an 'Evidence to Care' conceptual model, as proposed in a recent study 1, could foster simultaneous generation of evidence and long-term implementation to bridge the gap between evidence and care, ultimately improving outcomes for patients with HF and SCD.

From the FDA Drug Label

The Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) was a randomized, double-blind trial comparing ivabradine and placebo in 6,558 adult patients with stable New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 bpm

The current research gaps in heart failure (HF) and sickle cell disease (SCD) are not directly addressed in the provided drug label.

• The label discusses a clinical trial (SHIFT) that investigated the use of ivabradine in patients with heart failure, but it does not mention sickle cell disease.
• The trial focused on the treatment of heart failure with ivabradine, and the results do not provide information on research gaps in either heart failure or sickle cell disease 2.

From the Research

Current Research Gaps in Heart Failure (HF) and Sickle Cell Disease (SCD)

• The diagnosis of SCD-associated cardiomyopathy, a major cause of reduced quality of life and early mortality in SCD patients, is challenging due to unusual echocardiographic features and the fact that the classical diagnosis algorithm for HF is generally not suitable in SCD patients 3.
• There is a need for improved phenotyping to identify SCD patients at an earlier stage of myocardial dysfunction, as HF is poorly recognized and mostly diagnosed at a late congestive stage in routine practice 3.
• Cardiopulmonary complications, including cardiomyopathy, diastolic dysfunction, pulmonary hypertension (PH), and sudden cardiac death, are the most common causes of morbidity and mortality in SCD patients, highlighting the need for early diagnosis and intervention 4.
• The insidious evolution of HF with preserved ejection fraction (HFpEF) in SCD patients differs from the relatively acute evolution of HF with reduced ejection fraction, and the presence of PH significantly reduces functional capacity and increases mortality 5.
• There is a need for a comprehensive understanding of the pathogenesis of cardiovascular complications associated with SCD, as well as the development of tools to facilitate early diagnosis and management of patients with SCD 6.

Knowledge Gaps in SCD-Associated Cardiomyopathy

• The pathophysiology of SCD-associated cardiomyopathy is not fully understood, and further research is needed to improve the prognosis and quality of life of SCD patients 3.
• The relationship between LV diastolic dysfunction, myocardial fibrosis, and the evolution of PH-HFpEF in SCD patients is not well understood, and further studies are needed to assemble what has been learnt from clinical and animal studies 5.

Future Research Directions

• Further investigations are needed to improve the diagnosis and management of SCD-associated cardiomyopathy, including the development of new therapeutic approaches 3.
• Research is needed to address the increasing rates of cardiopulmonary complications in SCD patients, including pulmonary hypertension, heart failure with diastolic dysfunction, and sudden death 6.