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Open research questions in Heart Failure Treatment and Management

89 unresolved questions extracted from the limitations and future-work sections of 778 Heart Failure Treatment and Management papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Several health systems have incorporated pharmacist-led medication optimization for HFrEF, but this has not been assessed in a randomized controlled trial (RCT).

    Pharmacist-led intervention for optimal heart failure medications: A pilot randomized controlled trial · 2026 · DOI

  • For this analysis, LTFU was defined as the absence of both a completed 6‐month assessment and any subsequent clinical follow‐up throughout the study (confirmation of vital status alone was insufficient).

    Lost to Follow‐Up in Pragmatic Trials With Remote Follow‐Up: Insights From CONNECT‐HF and TRANSFORM‐HF · 2026 · DOI

  • In the future, longitudinal studies with larger samples should be conducted to increase the generalizability of these findings and the effects of psychosocial factors on quality of life should be examined in detail. Therefore, the findings are limited to this study group only and have limited generalizability.

    Factors Affecting Quality of Life in Heart Failure Patients: Nutrition, Anthropometric Measurements and Individual Variables · 2026 · DOI

  • Abstract Background The ratio of serum sodium to log(D-dimer) (log-SDR) in different types of chronic heart failure (CHF) is not well established.

    Predictive value of the serum sodium to log(D-dimer) ratio for the risk of all-cause death in patients with chronic heart failure with different ejection fractions · 2026 · DOI

  • No pre-specified safety event (KDIGO >or=1 AKI, hyperkalemia, hyponatremia, symptomatic hypotension) was detected (0/8 post-adjustment draws in 5/21 patients; exact 95% CI 0-37%); laboratory ascertainment was sparse, so a meaningful harm rate cannot be excluded.

    SURPASS-HF: Safety and Utility of Remote Pulmonary Artery Sensor Shared-management in Heart Failure · 2026 · DOI

  • 1 The health-promoting behaviors of CHF patients have not reached an ideal level The results showed that the overall level of health-promoting behaviors among patients with CHF was moderate, suggesting that most patients had not yet established stable and optimal health behavior patterns in daily disease management.

    Health literacy, social support, and health activation as determinants of health-promoting behaviors in patients with chronic heart failure: a COM-B model–based path analysis · 2026 · DOI

  • No. 9-01 Future clinical trials in HF should preferentially classify patients as HFrEF (LVEF <50%) or HFpEF (LVEF ≥50%). 9-02 Patients with LVEF 41–49% should generally be included within HFrEF trial populations, unless there is a specific scientific rationale otherwise. 9-03 Future therapeutic trials may alternatively enroll patients across the entire LVEF spectrum or according to underlying disease phenotypes and evaluate treatment effects continuously rather than using arbitrary EF categories. R: Recommend; Su: Suggest; HFrEF: Heart Failure with reduced ejecGon fracGon; LVEF: leI ventricular ejecGon fracGon; HFpEF: heart failure with preserved ejecGon fracGon.

    Draft Document for Public Consultation: What is new and what has changed in the 2026 Global Heart Failure Implementation Guidelines and why · 2026 · DOI

  • No. 8-08A 8-08B 8-09 Influenza vaccination once yearly (preferably at high dosages) in patients with HF in accordance with local vaccination policies and regional public health recommendations. Pneumococcal vaccination in eligible patients with HF, preferably as a single-dose higher-valent conjugate vaccine (e.g., PCV20 or PCV21) where appropriate, in accordance with regional and national vaccination schedules.. Administer COVID-19 vaccination in patients with HF in accordance with current regional and national public health recommendations to reduce the risk of severe infection, hospitalization, and cardiovascular complications. 8-10 Consider herpes zoster (shingles) vaccination in eligible patients with HF according to age-based and regional vaccination recommendations. 8-11 Consider respiratory syncytial virus (RSV) vaccination in eligible patients with HF according to age-based and regional vaccination recommendations.

    Draft Document for Public Consultation: What is new and what has changed in the 2026 Global Heart Failure Implementation Guidelines and why · 2026 · DOI

  • No. 4-17 4-19A 4-19B Use oral soluble guanylate cyclase stimulator (vericiguat) to reduce HF hospitalization and CV death with HFrEF and recent worsening of HF despite GDMT who have a NT-proBNP <6,000 pg/mL. Use low dose digoxin or digitoxin (target serum concentration 0.5-0.9 ng/mL)_ in patients with HFrEF who remain symptomatic despite GDMT as tolerated to decrease worsening HF events and HF hospitalization. If feasible, perform a plasma digitoxin / digoxin level assessment approximately 4–6 weeks after initiation or dose adjustment, while recognizing that earlier assessment may be appropriate when clinically indicated, to guide therapy and reduce the risk of toxicity. Particularly this should be considered for patients with low BMI and CKD.

    Draft Document for Public Consultation: What is new and what has changed in the 2026 Global Heart Failure Implementation Guidelines and why · 2026 · DOI

  • To enhance long-term outcomes in this population, we recommend routine screening for adherence barriers with standardized assessment (e.g., MMAS-8) and corresponding patient-centered individualized counseling, development of multilingual patient the education programs specifically addressing knowledge gaps in GDMT, cost subsidization programs to alleviate medication access issues, standardized post-discharge follow-up protocols at 1 and 3 months, and the conduct of multicenter prospective studies utilizing objective adherence assessment methods. Additionally, future studies must obtain serial blood pressure, BNP/NT-proBNP, troponin, eGFR, and electrolytes pre-GDMT and at 3 and 6 months thereafter for an objective assessment of adherence-related changes in cardiac remodeling and end-organ function, in addition to NYHA/QOL assessments. ACKNOWLEDGMENTS The presented data was abstracted from a dissertation submitted by Naz M. Abbas to the Kurdistan Higher Council of Medical Specialties (KHCMS) as a partial requirement for the Clinical Pharmacy fellowship.

    Adherence to Guideline-Directed Medical Therapy and its Impact on Clinical Outcomes in Heart Failure Patients Admitted to a Teaching Hospital · 2026 · DOI

  • 10 mg once daily Outpatient or inpatient (stable) ≥25–30 mL/min/1.73 m² Baseline, 2–4 weeks, then 3–6 monthly Hygiene + antifungal as needed Sick day rules, ketone…

    CLINICAL OUTCOMES OF DAPAGLIFLOZIN IN HEART FAILURE WITH REDUCED EJECTION FRACTION: A COMPREHENSIVE REVIEW · 2026 · DOI

  • The relative contribution of clinical stability variables versus co-prescribed guideline-directed medical therapy (GDMT) to confounding has not been directly quantified in this setting.

    In-hospital SGLT2 inhibitor initiation, prescribing gaps, and 30-day all-cause readmission in heart failure with reduced ejection fraction: a US post-guideline cohort study · 2026 · DOI

  • Funding The current analysis is based on a national administrative database which collects discharge reports. Consequently, it lacks granularity of in-hospital clinical data (e.g., HF etiology, phenotype, disease severity, or treatment). Overall, in administrative datasets, the validity for HF diagnosis varies, with high specificity—most recorded cases represent true HF—but low sensitivity, as many true cases are missed or underreported. Also, it has restricted ability to assess long-term outcomes beyond hospital readmissions. However, Research funded by Novartis Pharma Services Romania SRL.

    Heart failure hospitalization in Romania – A national multiannual study based on administrative dataset collection · 2026 · DOI

  • Apply AHF nursing guidelines in ED and CCU to im- prove respiratory status. Provide educational materials for nurses in both units. Replicate the study with larger, geographically diverse samples in Egypt.

    Improving Respiratory Status Among Patients With Acute Heart Failure by Implementing Nursing Guidelines · 2026 · DOI

  • Background The clinical significance of β 1 AR‐AAb (β 1 ‐adrenergic receptor autoantibody) subclasses, particularly IgG3 (immunoglobulin G subclass 3), in contemporary populations with HF (heart failure) remain unclear, especially in relation to β‐blocker therapy and HF phenotype.

    Subclass‐Specific Impact of β <sub>1</sub> ‐Adrenergic Receptor Autoantibodies and Phenotype‐Specific Interaction With β‐Blockers in a Contemporary Population With Heart Failure · 2026 · DOI

  • Background/Objectives: Telemedicine and remote patient monitoring have emerged as promising strategies to improve outcomes in heart failure (HF), but prior meta-analyses reported conflicting results, partly due to insufficient differentiation between intervention modalities.

    Digital Health Strategies in Heart Failure: Effects of Telemedicine and Remote Monitoring on Clinical Outcomes—A Systematic Review and Meta-Analysis · 2026 · DOI

  • This study has several notable strengths. It is one of the first investigations in Indonesia to systematically quantify the prevalence and determinants of excessive polypharmacy among HF patients using a clinically verified cohort with comprehensive medication documentation. The use of real-world data extracted from EMR enhances the validity and applicability of the findings to current clinical practice. Furthermore, the application of multivariate logistic regression analysis provides robust identification of independent predictors of excessive polypharmacy, minimizing confounding effects from demographic and comorbidity-related variables. Nevertheless, several limitations should be acknowledged. First, the cross-sectional design precludes causal inference regarding the temporal relationship between comorbidities the development of excessive polypharmacy. Future and 122 longitudinal or prospective studies are needed to determine whether polypharmacy directly contributes to adverse clinical outcomes, such as hospitalization, medication non-adherence, or mortality. Second, this study was conducted at a tertiary cardiovascular referral center; the patient population was predominantly composed of individuals with CAD and complex cardiovascular conditions. Therefore, referral bias may exist, and the medication burden observed in this cohort may not fully represent community-based or primary care HF populations. Despite these limitations, the study provides an essential early framework for understanding the multidimensional determinants of excessive polypharmacy in HF within an Indonesian healthcare context. It establishes a basis for future multicenter, longitudinal, and interventional studies aimed at evaluating deprescribing strategies, clinical outcomes, and the cost-effectiveness of integrated polypharmacy management programs.

    Excessive Polypharmacy Among Indonesian Heart Failure Patients: Clinical Correlates and Care Implications · 2026 · DOI

  • The included trials in our review have notable limitations. First, heterogeneity in patient population: some trials included CHF patients, while in others, some additional diseases were to be met for inclusion, these include type 2 diabetes mellitus (T2DM), and clinical symptoms of current fluid overload. Moreover, different definitions of HF were used, and the range of loop diuretics were broad, and some were only present in one RCT limiting our data synthesis. In addition, different HF definitions were included as well as different HF phenotypes. This heterogeneity may affect the pooled estimates, as differences in patient characteristics and disease severity may lead to variation in treatment response across studies. As a result, pooling these studies may obscure potential differences between loop diuretics. In 3 trials, the loop diuretics were administered intravenously and not orally in CHF patients, contributing to heterogeneity. This difference in route of administration may influence pharmacokinetics and thereby drug exposure and clinical response. Additionally, follow-up time varied from 2 days to 4 years. This reflects substantial methodological heterogeneity across trials, including differences in treatment duration and clinical setting. Sensitivity analyses excluding intravenous trials were not performed due to the limited number of available trials. Also, the absence of dose-adjusted analyses represent a limitation of this study, as differences in outcomes may partly reflect variation in dosing rather than differences in loop diuretics. A post-hoc analysis of the TRANSFORM-HF study demonstrated that higher loop diuretic dosage was associated with 40–58% relative increase in all-cause mortality compared to those receiving low dosage. These findings are independent of type of loop diuretic. A limitation to this finding is that the dosing of loop diuretic was not randomised, thus those receiving high dosages required high dosage, and are theoretically more decompensated, which itself proposes as a risk factor for death; this introduces confounding by indication in the post-hoc analysis. However, Terrovitis et al. randomised CHF patients, who were already on > 120 mg of furosemide to either maintenance dosage 1 3European Journal of Clinical Pharmacology (2026) 82:150 or a reduction with similar findings in all-cause mortality and more hospitalisations in the maintenance dose group. Here dosing but not type of diuretics was randomised, which eliminates the confounding found in the post-hoc analysis of TRANSFORM-HF. Only 4 trials contributed to the analysis of SAEs.

    Comparison of loop diuretics for chronic heart failure: a systematic review and meta-analysis · 2026 · DOI

  • Strengths This study has several notable strengths. First, it represents the first comprehensive characterization of heart failure epidemiology, clinical presentation, and outcomes at CHUMT, providing essential baseline data for quality improvement initiatives and health policy planning. Second, all cases were confirmed by echocardiography, ensuring diagnostic accuracy and allowing detailed characterization of cardiac structure and function. Third, the three-year study period provides a substantial sample size and reduces the impact of seasonal or temporal variations. Fourth, the use of multivariate analysis allowed identification of independent prognostic factors while controlling for confounding variables. Fifth, the study adhered to contemporary international guidelines for heart failure definition and classification [1].

    Epidemiological and Clinical Profile of Heart Failure at the Morafeno University Hospital of Toamasina, Madagascar: A Three-Year Retrospective Study · 2026 · DOI

  • The referenced cluster-randomized controlled trial (TRICORDER, reference 22) evaluating AI-enabled stethoscope triple cardiovascular disease detection does not specify how explainable AI methods will be integrated to ensure clinician understanding and adoption of AI predictions at the bedside, which is critical for early heart failure detection workflows.

    Artificial intelligence in early heart failure detection: from algorithms to bedside integration · 2026 · DOI

  • The smartwatch ECG feasibility study (reference 18) for predicting heart failure rehospitalization lacks specification of required wearable sensor accuracy specifications, data transmission reliability standards, and real-time processing latency thresholds necessary for clinical deployment in continuous AI-enabled cardiovascular monitoring.

    Artificial intelligence in early heart failure detection: from algorithms to bedside integration · 2026 · DOI

  • The excerpt references AI-enabled ECG screening for asymptomatic left ventricular dysfunction (reference 5, 14) but does not specify optimal screening intervals or risk stratification thresholds needed to transition from opportunistic screening to systematic population-based screening protocols for early heart failure detection.

    Artificial intelligence in early heart failure detection: from algorithms to bedside integration · 2026 · DOI

  • The differentiation between transient serum creatinine elevation representing hemodynamic changes versus clinically actionable cardio-renal pathology remains methodologically challenging and lacks validated diagnostic criteria. This phenotyping challenge directly affects appropriate patient selection for device therapy, requiring development of biomarkers or hemodynamic measures that reliably distinguish reversible from irreversible renal injury.

    Device-based therapies in cardio-renal syndrome: a pathophysiology-driven approach to a complex bidirectional disease · 2026 · DOI

  • Operator experience and procedural learning curves significantly influence outcomes for innovative cardio-renal syndrome devices, yet standardized training protocols and competency benchmarks for device insertion and hemodynamic adjustment are not established. The scalability of device-based CRS management beyond specialized centers requires structured operator training frameworks and protocol refinement documentation.

    Device-based therapies in cardio-renal syndrome: a pathophysiology-driven approach to a complex bidirectional disease · 2026 · DOI

  • Device-based therapies for cardio-renal syndrome are primarily investigational with limited integration into established clinical care pathways. Evidence demonstrating the efficacy of specific device types (pullers, reducers, pushers, interstitial modulators, fluid redistribution devices) matched to pathophysiologic phenotypes remains insufficient, requiring comparative effectiveness studies in specialized heart failure centers.

    Device-based therapies in cardio-renal syndrome: a pathophysiology-driven approach to a complex bidirectional disease · 2026 · DOI

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89 open questions have been extracted from the limitations and future-work passages of 778 Heart Failure Treatment and Management papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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