JoAnn Lindenfeld

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.

We developed a physiologically grounded metric—the Delta Myocardial Stress Index (ΔMSI)—to estimate myocardial oxygen supply-demand imbalance during the donor agonal phase and evaluated its association with posttransplant graft dysfunction. We performed a retrospective single-center study of adult donation after circulatory death (DCD) heart transplants (February 2020–June 2025). High-resolution hemodynamic data from withdrawal to declaration of death (WTD) were analyzed. Delta Myocardial Stress Index, integrating myocardial oxygen supply-demand balance, was derived from available hemodynamic data. Associations between ΔMSI and severe primary graft dysfunction (PGD) were assessed. Among 191 cases (16 severe PGD events), ΔMSI trajectories were significantly elevated in donors who developed severe PGD ( p < 0.001). Two distinct ΔMSI trajectory phenotypes were identified; high ΔMSI was independently associated with severe PGD (odds ratio [OR]: 2.49, p = 0.02) and 90 day mortality (OR: 4.58, p = 0.03). The association between WTD and PGD operated primarily through cumulative ΔMSI burden ( p = 0.02), whereas WTD alone was not associated with PGD after accounting for ΔMSI ( p = 0.25). Delta Myocardial Stress Index provides a noninvasive quantification of myocardial stress during DCD withdrawal. Myocardial stress, rather than agonal duration alone, was associated with severe PGD. These findings support a shift from time-based thresholds toward physiologic assessment of donor myocardial resilience.

BACKGROUND: While clinical benefits of guideline-directed medical therapy in patients with heart failure (HF) are well established, acute hemodynamic changes after initiation of these agents are not well described. Wireless pulmonary artery pressure (PAP) monitoring using implantable sensors is ideally suited to determine changes in pressure following medication titration. METHODS: We compared PAP from 7 days pre-initiation to the 7-day period following 30 days of newly initiated treatment with core HF therapies: angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, sodium-glucose co-transporter-2 inhibitors, and β-blockers in patients implanted with a PAP sensor (CardioMEMS, Abbott) as part of the GUIDE-HF study (Hemodynamic-Guided Management of HF). Patients with changes in loop diuretics or other core HF therapies during the 30-day interval were excluded from the analysis. RESULTS: Of 2358 patients in the study, 50 patients had new angiotensin receptor-neprilysin inhibitor initiation, 97 patients had new sodium-glucose co-transporter-2 inhibitor initiation, 112 patients had new mineralocorticoid receptor antagonist initiation, and 33 had new β-blocker initiation at least 30 days post-implant, continued to take the medication for at least 30 days, and were included in this analysis. Following angiotensin receptor-neprilysin inhibitor or mineralocorticoid receptor antagonist initiation, diastolic PAP decreased by −1.56 (95% CI, −3.54 to −0.40) and −1.15 (95% CI, −1.82 to −0.47) mm Hg, respectively, in the absence of changes in loop diuretics or other core HF therapies. By contrast, there was no detectable change in PAP following the new initiation of the sodium-glucose co-transporter-2 inhibitor. A trend to higher PAP was observed after β-blocker initiation though differences were not significant. CONCLUSIONS: These results may inform the selection of pharmacological therapy to manage elevated filling pressures during hemodynamic-guided therapy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03387813.

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.