William T. Abraham

Aims: Circadian patterns influence cardiovascular physiology, yet have not been characterized in intracardiac pressures of ambulatory chronic heart failure patients. We aimed to assess diurnal variation via a novel remote intracardiac left atrial pressure sensor. Methods and results: Daily ambulatory left atrial pressure (LAP) measurements were obtained with an implantable intracardiac sensor. Patients performed morning and evening measurements during longitudinal follow-up. We compared diurnal variability in morning and evening LAP, examined its potential association with diuretic regimen, presence of atrial fibrillation, and acute decompensated heart failure (ADHF) events. Across >15 500 measurement days with an average follow up time of 25.5 ± 18.6 months in 73 heart failure patients, median left atrial pressure was higher in the evening than in the morning [12.4 (6.8, 18.3) vs 10.7 (5.5, 17.3) mmHg; P < .01]. Neither higher diuretic dose, twice-daily dosing, nor atrial fibrillation modified this diurnal variation (P = .98, P = .50). Patients who suffered ADHF events demonstrated higher left atrial pressures [14.3 (9.5, 19.9) vs 10.4 (5.4, 17.3) mmHg, P < .01]. Higher LAP was also independently associated with increased risk of ADHF events (OR 1.40, 95% CI 1.10–1.78; P < .01). Diurnal variation was present irrespective of acute decompensated heart failure status (P = .79). Conclusions: Using direct ambulatory intracardiac LAP monitoring, we observed consistent diurnal variation with higher evening pressures, largely unchanged by diuretic dose or dosing schedule, atrial fibrillation, or association with ADHF events. Trial registration numbers: NCT03775161, NCT05448833, NCT05712824, NCT06147336.

Central sleep apnoea (CSA) and Cheyne–Stokes respiration are prevalent in patients with heart failure and contribute to disease progression, increased risk of death, heart failure hospitalisations and reduced quality of life. The 2025 American Academy of Sleep Medicine Clinical Practice Guideline for the Treatment of Central Sleep Apnea in Adults represents a major advance, recognising transvenous phrenic nerve stimulation as an evidence-based therapy for adults with CSA, including those with heart failure, as well as updating the clinical data on adaptive servo-ventilation. This review summarises key updates in the American Academy of Sleep Medicine 2025 guideline, examines the pathophysiological link between CSA and heart failure, and evaluates the clinical evidence and practical considerations for treatment. Current evidence indicates improvements in apnoea indices, oxygenation and quality of life, while the effect on mortality and hospitalisation needs additional prospective randomised data. Identification of patients with signs and symptoms which are likely due to central sleep apnoea is often missed in clinical practice, and treatment has a significant impact on quality of life.

BACKGROUND: Among 508 patients randomized to interatrial shunt implantation versus a placebo procedure in the RELIEVE-HF trial (Reducing Lung Congestion Symptoms Using the V-Wave Shunt in Advanced Heart Failure), 2-year clinical outcomes were improved in heart failure with reduced ejection fraction (HFrEF, n=206) and worsened in heart failure with preserved ejection fraction (HFpEF, n=302). However, randomized trials typically include therapeutic responders and nonresponders. We sought to determine the independent predictors of outcomes and model individual patient risk after atrial shunt implantation in HFrEF and HFpEF. METHODS: The primary outcome included all-cause death, cardiac transplantation or left ventricular assist device implantation, heart failure hospitalizations, and outpatient worsening heart failure events. From 37 baseline clinical, laboratory, echocardiographic, and hemodynamic covariates, the cumulative mean function of recurrent events during follow-up was modeled by the Lin-Wei-Yang-Ying method. RESULTS: Among control patients with HFrEF, independent baseline predictors of outcomes were atrial fibrillation, elevated troponin, lower left ventricular ejection fraction, and greater right atrial pressure. In contrast, independent predictors of outcomes in shunt-treated patients with HFrEF were lower systolic blood pressure and elevated right ventricular end-diastolic area index, pulmonary artery pressure, and pulmonary vascular resistance. Among control patients with HFpEF, independent predictors of outcomes were diabetes, higher heart rate and left ventricular end-systolic volume, and lower right ventricular fractional area change. Conversely, independent predictors in shunt-treated patients with HFpEF were hypertension, smoking, lower 6-minute walk distance, reduced estimated glomerular filtration rate, elevated troponin, and moderate or greater tricuspid regurgitation. Risk modeling estimated that 67.2% of patients with HFrEF might benefit from shunt placement compared with 21.4% of patients with HFpEF. CONCLUSIONS: In RELIEVE-HF, distinct baseline risk factors influenced cardiovascular outcomes before and after atrial shunt treatment in HFrEF and HFpEF. Despite markedly different group responses to atrial shunt treatment in the randomized HFrEF and HFpEF strata, given individual differences in patient risk factor profiles, most but not all patients with HFrEF may benefit, and some patients with HFpEF may also improve after shunt treatment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03499236.

Background: FIX-HF-5C multicenter, randomized study demonstrated cardiac contractility modulation (CCMTM) improved patient-centered outcomes, including functional capacity, symptom burden, and health-related quality of life. Reductions in cardiovascular death and heart failure hospitalization (HFH) were observed. These event-driven outcomes were not prespecified efficacy endpoints and were not incorporated into overall assessment of treatment benefit. Comprehensive clinical benefit of CCM therapy was re-analyzed by a win-ratio method that integrated event-driven clinical endpoints with patient-centered outcomes. Methods: The hierarchical win-ratio prioritized cardiovascular mortality, HFH, and patient-centered outcomes comprising equally weighted components of peak oxygen consumption, Minnesota Living with Heart Failure Questionnaire score, 6-minute walk distance, and NYHA functional class. Sub-group analyses were performed in patients with NYHA Class III versus IV. Results: In the primary analysis of 160 randomized patients (6,364 patient pairs), the overall win ratio was 2.48 (95% CI 1.76 to 3.64; p < 0.001), corresponding to a 71% pairwise comparative probability of clinical benefit with CCM versus OMT. Event-driven clinical endpoints accounted for 22% of total wins while 56.2% came from patient-centric endpoints. CCM consistently outperformed OMT across all hierarchies. Sensitivity analyses yielded similar findings with win ratios favoring CCM (range: 1.52 to 2.42). Treatment effects were consistent across NYHA class III and IV subgroups. Conclusions: The win-ratio re-analysis supports and extends the original study results demonstrating a consistent clinical benefit of CCM therapy over OMT across a hierarchical framework integrating event-driven clinical endpoints with patient-centered functional outcomes. The findings, while clinically highly encouraging, are hypothesis-generating and warrant validation in future confirmatory study.

Background: Ischemic heart disease (IHD) presents a growing global health burden across diverse geographic and socioeconomic settings. Clinical practice guidelines are typically developed by professional societies in high-income countries, often with limited consideration of implementation barriers in other healthcare settings. We sought to understand clinicians' use of IHD guidelines in their practice, perceived deficiencies, implementation barriers, and differences between doctors practicing in high-income countries (HIC) or in low-/middle-income countries (LMIC).Methods: An internet-based, international survey of physicians treating patients with IHD, (July 26, 2025-November 15, 2025), inquiring about participants' demographics, experience, and views of IHD guidelines as related to their practice.Results: Responses were provided by 587 clinicians from 97 countries. Approximately half (51.8%) considered the IHD guidelines as mostly or fully applicable in their country, a view more preponderant in HIC (67.3%) than in LMIC (48.8%; p=0.0125). Most (63.2%) thought IHD guidelines were highly applicable in HIC, but only 9.0% deemed the same for LMIC. The greatest barriers to guideline implementation were their being mostly relevant for HIC (72%), and cost, with the latter selected more frequently by the LMIC than the HIC group (61.7% v 20.4%; p<0.00001). Desires for future guidelines included availability in digital format, and inclusion of co-authors from LMIC.Conclusions: Survey respondents indicated that current IHD guidelines do not address the needs of clinicians and patients in LMIC as effectively as they do for those in HIC. Respondents advocated for future guidelines to have specific recommendations for differing socio-economic environments, and consideration of cost reimbursement.

Background: Persistent congestion at discharge is associated with worse outcomes in acute decompensated heart failure (ADHF), with impaired lymphatic function contributing to difficult-to-target tissue and organ congestion. Methods: The safety and effectiveness of the eLym System in ADHF were evaluated in the multicentre, single-arm DELTA-HF trial. A localized reduced-pressure zone at the venous angle was created in 40 patients using an endovenous axial pump to support lymph drainage through the thoracic duct. Results: Forty patients with ADHF (32.5% female, 71 ± 11 years) received therapy. Patients had a median of two hospitalizations in the prior 6 months. All were on home daily loop diuretic dose equivalent to ≥80 mg furosemide. Device deployment was successful in all cases (therapy time: 23.1 ± 7.3 h). Weight decreased by 3.6 ± 2.4 kg during eLym therapy and by 6.8 ± 3.4 kg at discharge. Median modified EVEREST Clinical Congestion Score improved from 5.0 (4.0–6.0) to 2.0 (1.0–4.0) after eLym treatment and to 0 (0–1.0) by discharge, remaining stable through 6 months (change from baseline P-values <.0001). Serum creatinine remained stable acutely and through 6 months. Freedom from device- or procedure-related serious adverse events was 95%. One patient had a vascular complication causing mediastinal haematoma and death; another required inotropes due to hypotension. At 6 months, two patients experienced three HF hospitalizations, and five patients died: four from cardiovascular causes; one from urosepsis. Conclusions: eLym therapy in ADHF appeared to be safe, with early data suggesting effective, durable decongestion and a low 6-month rehospitalization rate. Randomized controlled trials evaluating eLym therapy are warranted.

Central sleep apnoea (CSA) is a common comorbidity in patients with heart failure. Due to its insidious and chronic nature, CSA often remains unrecognised. Patients with CSA typically present with symptoms, such as daytime fatigue, recurrent heart failure decompensations and cardiac arrhythmias. Although the pathophysiology of CSA is not yet fully understood, the most widely accepted theory suggests that fluctuations in PaCO2 levels, particularly crossing the apnoeic threshold, play a central role in its development. CSA is associated with various changes, including activation of the sympathetic nervous system, neurohormonal disturbances and haemodynamic perturbations, all of which contribute to increased morbidity and mortality. Transvenous phrenic nerve stimulation (TPNS) has been demonstrated to be a safe and effective therapy for reducing the apnoea–hypopnoea index and improving both left ventricular ejection fraction and quality of life in patients with CSA. These benefits have been validated in randomised clinical trials (RCTs). New methods of analysing RCTs were recently introduced. Applying the win ratio method in a post hoc analysis of the primary RCTs evaluating TPNS suggested that TPNS may also contribute to reduced mortality and fewer heart failure hospitalisations. In this article we explore the pathophysiology of CSA and evaluate the existing evidence on therapeutic options, with a particular focus on TPNS.

BACKGROUND: The clinical significance of elevated baseline natriuretic peptide level and prior heart failure hospitalization (HFH) within the prior year in mitral transcatheter edge-to-edge repair outcomes is unclear. This analysis examined the impact of BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal pro-B-type natriuretic peptide) and prior HFH on outcomes in patients with severe secondary mitral regurgitation. METHODS: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) was a randomized controlled trial of subjects assigned to mitral valve transcatheter edge-to-edge repair with the MitraClip device versus guideline-directed medical therapy alone. COAPT patients were grouped by BNP/NT-proBNP levels and prior HFH within 1 year: (1) Mild heart failure (HF): no prior HFH with BNP/NT-proBNPP _trend =0.001). These rates were 48.7% and 73.4% among patients with moderate HF and a prior HFH only versus elevated BNP/NT-proBNP≥median only ( P =0.003). Mitral transcatheter edge-to-edge repair reduced death/HFH compared with guideline-directed medical therapy alone regardless of HF severity ( P _interaction =0.50). CONCLUSIONS: In patients with HF with severe secondary mitral regurgitation enrolled in the COAPT trial, 2-year rates of death/HFH were increased with an elevated baseline BNP/NT-proBNP≥median, and more so if HFH within 1 year prior had occurred. Treatment with mitral transcatheter edge-to-edge repair reduced all-cause mortality and HFH consistently in mild, moderate, and severe HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01626079.