Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial.

BACKGROUND: Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. METHODS: This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. FINDINGS: Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. INTERPRETATION: Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. FUNDING: Medtronic.

Association Between the Use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Health Care Use and Cost.

OBJECTIVES: To assess the association between the use of adaptive pacing on clinical and economic outcomes of cardiac resynchronization therapy (CRT) recipients in a real-world analysis. BACKGROUND: The adaptivCRT (aCRT) algorithm was shown in prior subgroup analyses of prospective trials to achieve clinical benefits, but a large prospective trial showed nonsignificant changes in the endpoint of mortality or hospitalizations due to heart failure. METHODS: CRT-implanted patients from the Optum Clinformatics database with ≥ 90 days of follow-up were included. Remote monitoring data were used to classify patients based on CRT setting-adaptive biventricular and left ventricular pacing (aCRT) vs standard biventricular pacing (Standard CRT). Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Mortality, 30-day readmissions, health care use, and payer and patients' costs were evaluated post-implantation. RESULTS: This study included 2412 aCRT and 1638 Standard CRT patients (mean follow-up: 2.4 ± 1.4 years), with balanced baseline characteristics after adjustment. The aCRT group was associated with lower all-cause mortality rates (adjusted hazard ratio = 0.88 [95% confidence interval (CI):0.80, 0.96]), fewer all-cause 30-day readmissions (adjusted incidence rate ratio = 0.87 [CI:0.81, 0.94]), and fewer all-cause and HF-related inpatient, outpatient and emergency department visits. The aCRT cohort was also associated with lower all-cause outpatient payer-paid amounts and lower all-cause and HF-related inpatient and emergency department patient-paid amounts. CONCLUSIONS: In this retrospective analysis of a large real-world cohort, the use of an adaptive CRT algorithm was associated with lower mortality rates, reduced health care resource use and lower payer and patient costs.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial.

BACKGROUND: Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients. METHODS: In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged ≥40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033. FINDINGS: Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1·0 [95% CI 0·8-1·2]; p=0·85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (pinteraction=0·002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=0·02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0·11). INTERPRETATION: Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. FUNDING: Corvia Medical.

A Review of Heart Failure in Patients with COVID-19.

The interplay of COVID-19 and heart failure is complex and involves direct and indirect effects. Patients with existing heart failure develop more severe COVID-19 symptoms and have worse clinical outcomes. Pandemic-related policies and protocols have negatively affected care for cardiovascular conditions and established hospital protocols, which is particularly important for patients with heart failure.

Machine learning method for predicting pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: An accurate assessment of permanent pacemaker implantation (PPI) risk following transcatheter aortic valve replacement (TAVR) is important for clinical decision making. The aims of this study were to investigate the significance and utility of pre- and post-TAVR ECG data and compare machine learning approaches with traditional logistic regression in predicting pacemaker risk following TAVR. METHODS: Five hundred fifity seven patients in sinus rhythm undergoing TAVR for severe aortic stenosis (AS) were included in the analysis. Baseline demographics, clinical, pre-TAVR ECG, post-TAVR data, post-TAVR ECGs (24 h following TAVR and before PPI), and echocardiographic data were recorded. A Random Forest (RF) algorithm and logistic regression were used to train models for assessing the likelihood of PPI following TAVR. RESULTS: Average age was 80 ± 9 years, with 52% male. PPI after TAVR occurred in 95 patients (17.1%). The optimal cutoff of delta PR (difference between post and pre TAVR PR intervals) to predict PPI was 20 ms with a sensitivity of 0.82, a specificity of 0.66. With regard to delta QRS, the optimal cutoff was 13 ms with a sensitivity of 0.68 and a specificity of 0.59. The RF model that incorporated post-TAVR ECG data (AUC 0.81) more accurately predicted PPI risk compared to the RF model without post-TAVR ECG data (AUC 0.72). Moreover, the RF model performed better than logistic regression model in predicting PPI risk (AUC: 0.81 vs. 0.69). CONCLUSIONS: Machine learning using RF methodology is significantly more powerful than traditional logistic regression in predicting PPI risk following TAVR.

Real-world behavior of CRT pacing using the AdaptivCRT algorithm on patient outcomes: Effect on mortality and atrial fibrillation incidence.

BACKGROUND: The AdaptivCRT (aCRT) algorithm continuously adjusts cardiac resynchronization therapy (CRT) according to intrinsic atrioventricular conduction, providing synchronized left ventricular pacing in patients with normal PR interval and adaptive BiV pacing in patients with prolonged PR interval. Previous analyses demonstrated an association between aCRT and clinical benefit. We evaluated the incidence of patient mortality and atrial fibrillation (AF) with aCRT compared with standard CRT in a real-world population. METHODS AND RESULTS: Patients enrolled in the Medtronic Personalized CRT Registry and implanted with a CRT from 2013-2018 were divided into aCRT ON or standard CRT groups based upon device-stored data. A Frailty survival model was used to evaluate the potential survival benefit of aCRT, accounting for patient heterogeneity and center variability. Daily AF burden and first device-detected AF episodes of various durations were recorded by the device during follow-up. A total of 1814 CRT patients with no reported long-standing AF history at implant were included. Mean follow-up time was 26.1 ± 16.5 months and 1162 patients (64.1%) had aCRT ON. Patient survival probability at 36 months was 88.3% for aCRT ON and 83.7% for standard CRT (covariate-adjusted hazard ratio [HR] = 0.71, 95% CI: 0.53-0.96, P = .028). Mean AF burden during follow-up was consistently lower in aCRT ON patients compared with standard CRT. At 36 months, the probability of AF was lower in patients with aCRT ON, regardless of which AF definition threshold was applied (6 minutes-30 days, all P < .001). CONCLUSION: Use of the AdaptivCRT algorithm was associated with improved patient survival and lower incidence of AF in a real-world, prospective, nonrandomized registry.

Changes in mechanical dyssynchrony in severe aortic stenosis patients undergoing transcatheter aortic valve replacement.

INTRODUCTION: Aortic stenosis (AS) imposes a significant afterload on the left ventricle, but regional manifestations of the overall load may not be uniform, leading to mechanical dyssynchrony. Accordingly, we evaluated the prevalence of dyssynchrony in patients with severe AS at baseline as well as changes after transfemoral aortic valve replacement (TAVR). METHODS: This study is a retrospective analysis of 225 patients in sinus rhythm who underwent TAVR for severe AS, in whom inter-ventricular and intra-ventricular dyssynchrony were measured at baseline, discharge, 1 month, and 1 year. Inter-ventricular dyssynchrony was defined as the difference between left and right ventricular pre-ejection intervals; intra-ventricular dyssynchrony was defined as the difference between time to peak systolic velocity of the basal septal and lateral segments. Patients were further stratified into those with QRS <120 ms or >120 ms. RESULTS: At baseline, a quarter of patients met the criterion for significant inter-ventricular dyssynchrony, and a third had evidence of intra-ventricular dyssynchrony. Both decreased after TAVR although only the intra-ventricular dyssynchrony reached statistical significance. The interplay between QRS duration and changes in inter- and intra-ventricular dyssynchrony are also explored. CONCLUSIONS: In patients with severe AS, there was evidence of mechanical dyssynchrony that is improved post-TAVR. Whether dyssynchrony is clinically and prognostically significant, and if it represents a potential target for additional therapy remains to be studied.

Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction.

AIMS: We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI). METHODS AND RESULTS: A total of 126 patients at 27 international sites within 10 days of onset of anterior or non-anterior MI with creatine phosphokinase >3000 U/L and QRS duration ≤120 ms were randomized 1:1:1 to dual-site biventricular pacing vs. single-site LV only pacing vs. non-implanted control. The primary endpoint was the echocardiographic core laboratory-assessed change in LV end-diastolic volume (ΔLVEDV) from baseline to 18 months between the pooled pacing therapy groups and the control group. ΔLVEDV increased by 15.3 ± 28.6 mL in the control group and by 16.7 ± 30.5 mL in the pooled pacing groups during follow-up (adjusted mean difference (95% CI) = 0.6 (-12.3, 13.5) mL, P = 0.92). There were also no significant between-group differences in the change in LV end-systolic volume or ejection fraction over time. Quality of life, as assessed by the Minnesota Living with Heart Failure (HF) and European Quality of Life-5 Dimension questionnaires and New York Heart Association class, was also similar between groups during 18-month follow-up. Six-minute walk distance improved during follow-up to an equal degree between groups, and there were no significant differences in the 18-month rates of death or HF hospitalization between the pooled pacing therapy vs. control groups (17.4 vs. 21.7% respectively, P = 0.59). CONCLUSIONS: In the present multicentre, randomized trial, peri-infarct pacing did not prevent LV remodelling or improve functional or clinical outcomes during 18-month follow-up in patients with large first MI. CLINICALTRIALSGOV IDENTIFIER: NCT01213251.

Biventricular pacing for atrioventricular block and systolic dysfunction.

BACKGROUND: Right ventricular pacing restores an adequate heart rate in patients with atrioventricular block, but high percentages of right ventricular apical pacing may promote left ventricular systolic dysfunction. We evaluated whether biventricular pacing might reduce mortality, morbidity, and adverse left ventricular remodeling in such patients. METHODS: We enrolled patients who had indications for pacing with atrioventricular block; New York Heart Association (NYHA) class I, II, or III heart failure; and a left ventricular ejection fraction of 50% or less. Patients received a cardiac-resynchronization pacemaker or implantable cardioverter-defibrillator (ICD) (the latter if the patient had an indication for defibrillation therapy) and were randomly assigned to standard right ventricular pacing or biventricular pacing. The primary outcome was the time to death from any cause, an urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the left ventricular end-systolic volume index. RESULTS: Of 918 patients enrolled, 691 underwent randomization and were followed for an average of 37 months. The primary outcome occurred in 190 of 342 patients (55.6%) in the right-ventricular-pacing group, as compared with 160 of 349 (45.8%) in the biventricular-pacing group. Patients randomly assigned to biventricular pacing had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing (hazard ratio, 0.74; 95% credible interval, 0.60 to 0.90); results were similar in the pacemaker and ICD groups. Left ventricular lead-related complications occurred in 6.4% of patients. CONCLUSIONS: Biventricular pacing was superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I, II, or III heart failure. (Funded by Medtronic; BLOCK HF ClinicalTrials.gov number, NCT00267098.).

Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial.

BACKGROUND: Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). METHODS: Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. RESULTS: Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met (P = 0.89). For the patients treated with pSDF-1, there was a trend toward an improvement in LVEF at 12 months (placebo vs. 15 mg vs. 30 mg ΔLVEF: -2 vs. -0.5 vs. 1.5%, P = 0.20). A pre-specified analysis of the effects of pSDF-1 based on tertiles of LVEF at entry revealed improvements in EF and LVESV from lowest-to-highest LVEF. Patients in the first tertile of EF (<26%) that received 30 mg of pSDF-1 demonstrated a 7% increase in EF compared with a 4% decrease in placebo (ΔLVEF = 11%, P = 0.01) at 12 months. There was also a trend towards improvement in LVESV, with treated patients demonstrating an 18.5 mL decrease compared with a 15 mL increase for placebo at 12 months (ΔLVESV = 33.5 mL, P = 0.12). The change in end-diastolic and end-systolic volume equated to a 14 mL increase in stroke volume in the patients treated with 30 mg of pSDF-1 compared with a decrease of -11 mL in the placebo group (ΔSV = 25 mL, P = 0.09). In addition, the 30 mg-treated cohort exhibited a trend towards improvement in NTproBNP compared with placebo at 12 months (-784 pg/mL, P = 0.23). CONCLUSIONS: The blinded placebo-controlled STOP-HF trial demonstrated the safety of a single endocardial administration of pSDF-1 but failed to demonstrate its primary endpoint of improved composite score at 4 months after treatment. Through a pre-specified analysis the STOP-HF trial demonstrates the potential for attenuating LV remodelling and improving EF in high-risk ischaemic cardiomyopathy. The safety profile supports repeat dosing with pSDF-1 and the degree of left ventricular remodelling suggests the potential for improved outcomes in larger future trials.

The Post-Myocardial Infarction Pacing Remodeling Prevention Therapy (PRomPT) Trial: Design and Rationale.

BACKGROUND: Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. METHODS: The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 µg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group. Those randomized to a device will be blinded to the pacing mode, but randomization to a device or control cannot be blinded. Subjects randomized to pacing will have the device implanted within 10 days of MI. The primary objective is to assess the change in left ventricular end-diastolic volume from baseline to 18 months. Secondary objectives are to assess changes in clinical and mechanistic parameters between the groups, including rates of hospitalization for heart failure and cardiovascular events, the incidence of sudden cardiac death and all-cause mortality, New York Heart Association functional class, 6-minute walking distance, and quality of life. CONCLUSIONS: The PRomPT trial will provide important evidence regarding the potential of peri-infarct pacing to interrupt adverse remodeling in patients with large MI.

The Relationship Among Heart Failure Disease Management, Quality of Care, and Hospitalizations.

Heart failure (HF) affects 5.1 million adult patients, accounting for over 1 million hospitalizations, 1.8 million office visits, and nearly 680,000 emergency department visits annually. HF hospitalizations have been incorporated into a national measure of hospital and provider quality, with associated financial penalties based on the 30-day readmission rate after an index hospitalization for HF. However, it is not clear whether the number of HF-related hospitalizations or 30-day readmissions is consistently related to quality of care. The relationships between various measures of HF care quality and hospitalization rates were evaluated by performing a cohort study of an HF disease management program in a clinical practice setting. Following the statistical analyses assessing outcomes and survival, the conclusion was that an HF disease management program in clinical practice associated with improved utilization of evidence-based medical and device therapies tends to improve ejection fraction and survival, and reduce sex and race disparities, but not with an associated reduction in hospitalizations or total hospital days.

The relationship between cardiac resynchronization therapy and diastolic function.

Cardiac resynchronization therapy (CRT) improves measures of systolic function and clinical status. However, its effect on diastolic function is not well established. Commonly used parameters of diastolic function are measured from echocardiography, using pulse wave and tissue Doppler technologies, as well as timing and deformation data. Review of the existing studies that address the relationship between diastolic function and CRT shows conflicting data, but general trends can be deduced. Baseline elevated filling pressure appears to identify patients most likely to derive improvement in that particular parameter. Intrinsic relaxation does not appear to be significantly impacted by CRT. Generally, changes in diastolic properties after CRT appear to be linked to changes in systolic function. Specific therapy aimed at diastolic asynchrony is lacking, partly due to an unclear relationship between diastolic asynchrony and diastolic dysfunction, and the inability to specifically impact diastolic timing with a systolic intervention such as CRT.

Management strategies and prognosis of patients ineligible for transcatheter mitral valve replacement.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) faces anatomical challenges, currently limiting widespread adoption. OBJECTIVES: To describe the natural history and prognosis of patients ineligible for various TMVR devices. METHODS: During a 4-year period (2019-2023) 3 TMVR devices (SAPIEN M3, Intrepid and Alta Valve) became available at a single institution (The Christ Hospital, Cincinnati, OH) in the setting of pivotal clinical trials or early feasibility study. Consenting patients who were deemed ineligible ≥1 of these trials were prospectively studied to capture anatomical reasons for ineligibility, cross-over to alternative mitral valve therapies (surgery or high-risk mitral transcatheter edge to edge repair [M-TEER]), and clinical events. RESULTS: A total of 61 patients (out of 71 consenting patients or 85.9 %) were deemed ineligible for TMVR during the study period. The mean age was 79.2 ± 8.8 years, 65.6 % were female, with elevated surgical risk (median STS 4.3, IQR: 2.7-7.3). The 2 most common anatomical reasons for ineligibility were increased risk of left ventricular outflow tract obstruction (LVOTO) (n = 24, 39.3 %) and annular size (n = 29, 47.5 %). During follow-up (median 277 [162-555] days) there were 7 deaths (11.5 %) and 12 (19.7 %) hospitalizations for heart failure. Management strategies included high-risk M-TEER in 11 patients (1 death [9.0 %], 0 HF hospitalizations [0 %]), surgery in 9 patients (0 deaths, 1 HF hospitalizations [11.1 %]), and medical management in 41 patients (6 deaths [14.6 %], 11 HF hospitalizations [26.8 %]) (p = 0.715 for mortality and p = 0.093 for HF hospitalizations). Residual MR ≥ moderate was 0 %, 50 %, and 100 % for surgery, M-TEER and medical treatment, respectively (p < 0.001). CONCLUSIONS: One third of patients deemed ineligible for TMVR are candidates for high-risk M-TEER or surgery with acceptable morbidity and mortality. Our results have practical implications for patient management.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II.

BACKGROUND: The REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, "responders" (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. OBJECTIVES: This study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. METHODS: The study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. RESULTS: In 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). CONCLUSIONS: At 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033).

Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

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) >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 >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 < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 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 < 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 >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.

Clinical response with adaptive CRT algorithm compared with CRT with echocardiography-optimized atrioventricular delay: a retrospective analysis of multicentre trials.

AIMS: Adaptive cardiac resynchronization therapy (aCRT) is a novel algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular (LV) or bi-ventricular (BiV) pacing and optimization of atrioventricular (AV) and inter-ventricular (VV) delays based on periodic measurement of intrinsic conduction. We aimed to compare the clinical response between aCRT and standard CRT in historical trials. METHODS AND RESULTS: The treatment arm of the aCRT trial was compared with a pooled historical control (HC) derived from the CRT arms of four clinical trials (MIRACLE, MIRACLE ICD, PROSPECT, and InSync III Marquis) with respect to the proportion of patients who had an improved clinical composite score (CCS) at the 6-month follow-up. Patients in the HC underwent echocardiography-guided AV optimization after the implant. A propensity score model was used to adjust for 22 potential baseline confounders of the effect of CRT. Patients were stratified into quintiles according to the propensity score and the adjusted absolute treatment effect was obtained by averaging estimates across these quintiles. The propensity score model included 751 patients (aCRT: 266, historical trials: 485). The adjusted absolute difference in percent improved in CCS between the aCRT and HC arms was 11.9% [95% confidence interval (CI): 2.7-19.2%] favouring aCRT. The patients in the aCRT group were significantly more likely to have an improved CCS than the patients in the HC (odds ratio = 1.65, 95% CI: 1.1-2.5). CONCLUSION: The aCRT algorithm may be associated with additional improvement in clinical response compared with historical CRT with echocardiographic AV optimization.

Alterations in early filling dynamics predict the progression of compensated pressure overload hypertrophy to heart failure better than abnormalities in midwall systolic shortening.

To evaluate whether the evolution of compensated pressure overload hypertrophy (POH) to overt heart failure (HF) is better predicted by systolic versus diastolic dysfunction, serial echocardiography was performed 1, 2, 4, 8, and 10 weeks after suprarenal aortic banding in 52 rats. One week after banding, at comparable extent of left ventricular hypertrophy and geometry, myocardial and chamber systolic performance, a restrictive filling pattern was well evident only in rats which eventually developed overt HF, according to postmortem lung weight. In experimental POH, early assessment of transmitral flow velocity allows to predict a faster progression toward HF.

Systolic Heart Failure is Associated with Higher Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Analysis.

Heart failure (HF) is prevalent among patients with aortic stenosis and presents a poor prognosis. In order to better portray outcomes for HF patients undergoing transcatheter aortic valve replacement (TAVR), we evaluated clinical outcomes in patients with systolic vs diastolic heart failure who underwent TAVR in a large nationwide database. We searched the National Inpatient Sample (NIS) for hospitalized adult patients who underwent TAVR with coexisting history of systolic (SHF) or diastolic heart failure (DHF) as a secondary diagnosis using the ICD-10 codes. The primary outcome was in-hospital mortality, with secondary outcomes of cardiac arrest (CA), cardiogenic shock (CS), respiratory failure (RF), Non-ST elevation myocardial infarction (NSTEMI), acute kidney injury (AKI), use of cardiac and respiratory assist device, and health care utilization defined as length of stay, average hospital cost (AHC) and patient charge (APC). Both univariate and multivariate logistic, generalized linear, and Poisson regression analyses were used to evaluate and test the outcomes. A P-value of <0.05 was significant. A total of 106,815 patients were admitted to acute care hospitals for TAVR, and 73% had a secondary diagnosis of heart failure (41% had SHF and 59% DHF). SHF group were older (mean age of 78.9 years [SD ± 8.9] vs 79.9 years [SD ± 8.3]) with more males (61.8% vs 48.2%) and white predominant (whites [85.9% vs 87.9%]). Compared to DHF, SHF had higher inpatient mortality (1.75% vs 1.14%, P = 0.003), CA (1.31% vs 0.81%, P = 0.01), NSTEMI (2.52% vs 1.0%, P = 0.001), RF (10.87% vs 8.01%, P = 0.001), and CS (3.94% vs 1.14%, P = 0.001). In addition, SHF had greater LOS (5.1 days vs. .3.9, P = 0.0001) & AHC ($52,901 vs $48,070, P = 0.0001). HF is common among patients admitted for TAVR. SHF had worse CV outcomes, greater use of hospital resources, and higher acute care hospital mortality compared to those with DHF.