Klein, Liviu

Abstract Aims Trends in upright seated pulmonary artery pressure (PAP) with synchronous measurement of weight, blood pressure (BP), and heart rate (HR) have not been compared prior to heart failure events (HFE) and other causes of hospitalization during remote monitoring. Methods We analysed 24-month data from patients in the PROACTIVE-HF trial. Participants (N = 456) used the CordellaTM HF daily to measure seated PAP, weight, BP, and HR, all taken and transmitted within minutes. Events that were analysed included HFE, those potentially related to HF treatment (HF-TRE), and others (non-HFE). Parameters were trended from 60-days before (D-60) to 30-days after (D + 30) the day of the event (D = 0), and their concurrent changes were compared between D-60 and D = 0, and D = 0 and D + 30 using a mixed effects model. Results There were 196 HFE, 276 non-HFE, and 66 HF-TRE. Prior to HFE, average mean PAP (mPAP) increased from 27.8 ± 10.9 mmHg at D-60 to 32.6 ± 11.2 mmHg at D = 0 (P < .001), and decreased to 30.0 ± 12.4 mmHg at D + 30 (P = .001). Kinetics of mPAP before HFE differed by left ventricular ejection fraction (LVEF); mPAP rose by 3.4 ± 6.8 mmHg in 2 weeks before HFE in those with LVEF >40%, whereas a similar magnitude (3.1 ± 9.1 mmHg) of mPAP rise occurred over 6-weeks before HFE in those with LVEF ≤40%. No consistent changes in weight, SBP, or HR prior to HFE were observed (P > .05). Changes in vital signs but not mPAP were noted prior to HF-TRE and non-HFE. Conclusion Seated mPAP increased weeks in advance of HFE and vital signs did not change consistently before HFE. Differential kinetics of mPAP prior to HFE by the LVEF suggest that an uptrend in seated mPAP may need to be addressed more rapidly in those with LVEF>40%. Changes in vital signs with non-HFE and HF-TRE need further validation.

BACKGROUND: A preservation system, the Organ Care System (OCS; TransMedics) uses normothermic pulsatile perfusion during organ transport for heart transplantation. This system has demonstrated favorable outcomes in hearts recovered from extended-criteria donors after brain death (DBD) and donors after circulatory death (DCD). METHODS: The OCS Heart Perfusion Registry collects data on US heart transplantations using the OCS, static cold storage (SCS), or thoracoabdominal normothermic regional perfusion (NRP) and donor hearts recovered from DBD or DCD donors. We analyzed donor and recipient characteristics and posttransplantation outcomes in patients transplanted with OCS donor hearts (either DBD or DCD) compared with SCS hearts, and with OCS hearts from DCD donors compared with those recovered with NRP followed by SCS. Propensity score matching was used in survival analyses to adjust for differences among recipient characteristics. RESULTS: Between 2021 and 2023, 3225 consecutive heart transplantations enrolled from 56 centers were analyzed in the Heart Perfusion Registry. The OCS was used in 854 of 3225 heart transplantations (26.4%), among which 340 (39.8%) were DBD and 514 (60.2%) were DCD donors, whereas 2174 DBD donors were recovered with SCS and another 197 DCD donors with NRP techniques. The OCS-DBD group experienced a greater number of organ offer refusals before final acceptance (13 versus 6; Wilcoxon rank sum, P <0.001) and a longer transport distance (667 miles versus 232 miles; Wilcoxon rank sum, P <0.001) compared with SCS-DBD. Survival at 12 months was similar between the 2 groups (89.9% for OCS-DBD versus 90.6% for SCS-DBD; marginal Cox model, P =0.54). Among the OCS-DCD and SCS-DBD groups, survival at 12 months was also similar (91.0% versus 92.5%, respectively; marginal Cox model, P =0.32). The OCS-DCD and NRP-DCD groups demonstrated similar survival (91.0% versus 91.7%, respectively; log rank, P =0.63), although the transport distance was longer in OCS-DCD compared with DCD with NRP followed by SCS (400 miles versus 223 miles; Wilcoxon rank sum, P <0.001). By 2023, 90% of all OCS donor management and recovery was performed with dedicated organ recovery teams. CONCLUSIONS: We demonstrate that real-world implementation of the OCS for DBD donors (using predominantly a dedicated recovery team) is associated with expanded donor criteria, longer transport distance, and excellent posttransplantation outcomes. In OCS-DCD donors, outcomes parallel those of donors recovered with NRP-DCD and compare favorably with DBD donor organs.

ImportanceGreater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF).ObjectiveTo explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM).Design, Setting, and ParticipantsThis was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024.InterventionSAVM vs sham control procedure.Main Outcomes and MeasuresThe primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP.ResultsA total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, −0.03 mm Hg; 95% CI, −2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, −6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, −9.2% to 18.8%; P = .48).Conclusions and RelevanceResults show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF.Trial RegistrationClinicalTrials.gov Identifier: NCT04592445

Abstract Aims Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. Methods and results Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) &gt;40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF &gt;40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was −5.7 (−8.6, −2.9) mmHg at 6 months (p &lt; 0.001). At baseline, 8% had New York Heart Association class I–II status and improved to 68% at 1 year (p &lt; 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20–30) and 27 (22–32) points, respectively (both p &lt; 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. Conclusions In patients with heart failure and LVEF &gt;40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Aims In heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll‐in cohort of the REBALANCE‐HF trial. Methods and results The open‐label (roll‐in) arm of REBALANCE‐HF will enrol up to 30 patients, followed by the randomized, sham‐controlled portion of the trial (up to 80 additional patients). Patients with HF, left ventricular ejection fraction (LVEF) ≥50%, and invasive peak exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg underwent SAVM. Baseline and follow‐up assessments included resting and exercise PCWP, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6‐min walk test, and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). Efficacy and safety were assessed at 1 and 3 months. Here we report on the first 18 patients with HFpEF that have been enrolled into the roll‐in, open‐label arm of the study across nine centres; 14 (78%) female; 16 (89%) in NYHA class III; and median (interquartile range) age 75.2 (68.4–81) years, LVEF 61.0 (56.0–63.2)%, and average (standard deviation) 20 W exercise PCWP 36.4 (±8.6) mmHg. All 18 patients were successfully treated. Three non‐serious moderate device/procedure‐related adverse events were reported. At 1‐month, the mean PCWP at 20 W exercise decreased from 36.4 (±8.6) to 28.9 (±7.8) mmHg ( p < 0.01), NYHA class improved by at least one class in 33% of patients ( p = 0.02) and KCCQ score improved by 22.1 points (95% confidence interval 9.4–34.2) ( p < 0.01). Conclusion The preliminary open‐label results from the multicentre REBALANCE‐HF roll‐in cohort support the safety and efficacy of SAVM in HFpEF. The findings require confirmation in the ongoing randomized, sham‐controlled portion of the trial.

Background: Heart failure (HF), a leading cause of morbidity and mortality in women, continues to disproportionately affect African-American (AA) women compared to women of other races/ethnicities. In a large cohort of post-menopausal women, we investigated if AA women progress through HF stages and coronary heart disease (CHD) death more rapidly than Caucasian (Cau) or Hispanic/Latina (HL) women. Methods: We assessed the American College of Cardiology/American Heart Association (ACC/AHA) HF stage A upon enrollment into the Women’s Health Initiative (1993-1998) and the progression from Stage A to Stage C, Stage C to CHD death, up to the last date of follow-up (2010). Cox proportional hazard regressions models were used to assess disease progression risk. We adjusted for age, baseline comorbidities, duration of comorbidities, interval development of myocardial infarction, ejection fraction at HF diagnosis, socioeconomic factors, and sex specific variables. Results: At baseline, AA women were younger and had a higher percentage of Stage A HF (76%) than Cau (54%) and HL (55%) women. Overall, AA and HL women had significantly lower risk of progressing from Stage A to Stage C compared to Cau women [AA vs. Cau adjusted Hazard Ratio (HR) 0.77 (95% Confidence Interval (CI) 0.64 -0.93) p = 0.0055; HL vs. Cau HR 0.54 (95% CI 0.40 -0.71) p < 0.0001]. After stratifying by age groups(<65, 65-69, >70 years), AA women had a similar risk of progression from stage A to C compared to Cau women. When compared to Cau women, AA had an insignificant increased risk of progressing from Stage C to CHD death [adjusted HR 1.29 (95% CI 0.72 -2.32) p = 0.3883)]. Conclusions: Cau women were at higher risk for HF progression from Stage A to Stage C compared to HL women, but at similar risk as AA women. AA women had an insignificant but increased risk of progression from Stage C to CHD death compared to Cau women.