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............................................................................................................................................................................. 16 Gaps in evidence

Major advances in the diagnosis and treatment of patients with HF have occurred over recent years. Strong evidence for new treatment options have been given by recent RCTs and HF management may undergo major changes in the next years. New discoveries, however, pose new challenges and many areas with lack of evidence still remain. The following is a short list of selected, common issues that deserve to be addressed in future clinical research.

(1) Definition and epidemiology

i. Further research into the underlying characteristics, pathophysiology, and diagnosis of HFmrEF and HFpEF ii. Consensus about normal values/ranges of EF iii. Better phenotyping of HFpEF iv. More information on the incidence and prevalence of ‘recovered LV’ systolic function (2) Diagnosis

i. Definitive studies on the role of biomarkers, focusing on their additive value in the diagnosis of HF ii. More randomized studies on screening for HF in asymptomatic subjects that may translate into improved outcomes iii. Studies on biomarkers showing the impact on outcome of their measurements for the identification of subjects at risk of developing HF as well as to guide treatment in patients with HF iv. Validated diagnostic protocols for the diagnosis of HFmrEF and HFpEF (3) Pharmacotherapy of CHF

i. Pragmatic studies on the order of adding disease-modifying drugs for HFrEF ii. Specific therapies for HFmrEF and HFpEF and, likely, their different phenotypes iii. More data and prospective clinical trials of HFrEF therapies in

patients with eGFR <30 mL/min/1.73 m2 iv. Further evidence from prospective RCTs for the treatment of specific HF phenotypes: myocarditis, cardiotoxicity, inherited CMPs, PPCM, amyloidosis v. Management strategies and therapies for ‘recovered LV’ systolic function vi. More evidence on the effects of fluid restriction, dietary salt restriction, and nutrition (4) Devices and interventions

i. Indications for ICDs in specific subgroups of HFmrEF/HFpEF and optimal selection of ICD candidates in HFrEF, including patients with ischaemic and non-ischaemic cardiomyopathy ii. More research on CRT efficacy in AF iii. Further prospective randomized studies showing the impact on outcomes of AF ablation strategies compared to OMT in HF patients iv. Further research on the percutaneous treatment of valve heart disease and its impact on patients’ outcomes and QOL v. Larger RCTs on CCM and baroreceptor stimulation in HFrEF (5) Disease management

i. The role of remote monitoring strategies in HF in the post COVID-19 era ii. Studies on optimal models for follow-up of stable HF patients iii. Studies to determine specific options for palliative care (6) Advanced HF

i. Better definition of risk profiles according to INTERMACS and other classifications ii. RCTs to establish the effects on outcomes of long-term MCS in hospitalized patients as well as in ambulatory outpatients (for instance INTERMACS 46 profiles) iii. Advances in long-term MCS, including strategies to reduce the risk of bleeding, thromboembolic events, and infection iv. Advances in medical treatment for the many patients who cannot undergo MCS or heart transplantation including development of treatment strategies, novel inotropes or myotropes for patients with advanced HF (7) AHF

i. Better definition and classification of patient phenotypes to facilitate improved treatment ii. Evidence-based use of imaging techniques and biomarkers that have an impact on patients’ clinical course iii. Development of better strategies for congestion relief, including monitoring of diuretic administration, and/or to improve organ perfusion iv. Identification of treatments with an impact on post-discharge outcomes v. New devices for short-term MCS vi. Definition of evidence-based treatment options and therapeutic algorithms for patients with cardiogenic shock (8) CV comorbidities

i. RCTs showing best strategies for the treatment of ventricular arrhythmias ii. RCTs to establish the role of coronary revascularization procedures in different patient subsets iii. RCTs to establish the impact on patients’ outcomes and/or

QOL of percutaneous treatment of mitral or tricuspid valve disease in patients with HF (9) Non-CV comorbidities

i. RCTs addressing cachexia and/or sarcopenia and/or frailty and showing the impact of treatment on QOL and/or outcome ii. RCTs of medical therapies or devices in patients with severe CKD and HF iii. RCTs showing the effects on outcomes of medical treatment of electrolyte abnormalities iv. RCTs showing the effects on outcomes of treatment of CSA v. Prospective studies showing the impact on outcomes and/or QOL of early diagnosis, better prevention and treatment of cardiotoxicity of cancer therapies vi. Better treatment of infections and prevention of cardiac injury with infection (10) Special conditions

i. RCTs of treatment for PPCM ii. Better phenotyping of CMPs through genetic testing, biomarkers and imaging modalities, and tailoring of therapy iii. RCTs of treatment of different types of myocarditis, including immunosuppressive therapies iv. RCTs of new treatments of different forms of cardiac amyloid v. Better definition and treatment of LA myopathy. Downloaded from academic.oup.com/eurheartj/article/42/36/3599/6358045 by guest on 07 October 2026