Significant Reverse Remodeling Research Articles

Effect of Ivabradine on Left Ventricular Reverse Remodeling in Relatively Stable Heart Failure Outpatients With Reduced Ejection Fraction.

Background: Elevations of resting heart rate (HR) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) are often missed, resulting in some patients with an indication for ivabradine reportedly being missed. Methods and Results: We studied 30 relatively stable HFrEF outpatients, and ivabradine was administered when regular follow-up echocardiography showed a resting HR ≥75 beats/min. Significant left ventricular reverse remodeling was observed 10.1±3.9 months after administration of ivabradine. Conclusions: This finding may well make this procedure a potential new approach for preventing worsening of HF for relatively stable patients with HFrEF.

Kiosk 4R-FB-06 - Contemporary Heart Failure Medical Therapy Results in Significant Left Ventricular and Left Atrial Reverse Remodelling in Patients with Severe Left Ventricular Systolic Dysfunction

Kiosk 4R-FB-06 - Contemporary Heart Failure Medical Therapy Results in Significant Left Ventricular and Left Atrial Reverse Remodelling in Patients with Severe Left Ventricular Systolic Dysfunction

Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure

Abstract Background Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. Since sacubitril/valsartan was reported to be more potent than renin-angiotensin-aldosterone system inhibitors for lowering blood pressure, HF patients with low blood pressure were not included in most clinical studies as a result of sacubitril/valsartan administration, and average systolic blood pressure of most enrolled patients was around 120 mmHg. Thus, the effect of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for HF patients with LVEF < 50% and low blood pressure, remains uncertain. Purpose The aim of this study was to examine the effect of sacubitril/valsartan on LV reverse remodeling after initiation of the maximum tolerated dose of sacubitril/valsartan for HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg, and a comparison of its efficacy with that for patients with systolic blood pressure > 100 mmHg. Methods We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. Results sacubitril/valsartan was discontinued for 17 (10.4%) as decided by the attending physician mainly due to hypotension. The prevalence of discontinuation of sacubitril/valsartan for the low blood pressure group was higher than that for the non-low blood pressure group, but the difference was not statistically significant (16.0% vs. 9.4%, P = 0.32). No serious adverse events occurred during this study. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group than for the non-low blood pressure group (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P<0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P<0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups (Figure). Conclusions Significant LV reverse remodeling can occur after initiation of sacubitril/valsartan even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg if tolerated. This finding is expected to offer new insights for better management of HF patients.Figure

CRT non-responder to responder conversion rate in the MORE-CRT MPP Trial.

To assess the impact of MultiPoint™ Pacing (MPP) in cardiac resynchronization therapy (CRT) non-responders after six months of standard biventricular pacing (BiVP). The trial enrolled 5,850 patients who planned to receive a CRT device. The echocardiography core laboratory assessed CRT response before implant and after six months of BiVP; non-response to BiVP was defined as < 15% relative reduction in left ventricular end-systolic volume (LVESV). Echocardiographic non-responders were randomized in a 1:1 ratio to receive MPP (541 patients) or continued BiVP (570 patients) for an additional six months and evaluated the conversion rate to the echocardiographic response. The characteristics of both groups at randomization were comparable. The percentage of non-responder patients who became responders to CRT therapy was 29.4% in the MPP arm and 30.4% in the BIVP arm (p=0.743). In patients with > 30 mm spacing between the two left ventricular pacing sites (MPP-AS), identified during the first phase as a potential beneficial subgroup, no significant difference in the conversion rate was observed. Our trial shows that approximately 30% of patients, who do not respond to CRT in the first six months, experience significant reverse remodeling in the following six months. This finding suggests that CRT benefit may be delayed or slowly incremental in a relevant proportion of patients and that the percentage of CRT responders may be higher than what has been described in short/middle-term studies. MPP does not improve CRT response in non-responders to BiVP, even with MPP-AS.

Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure.

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100mmHg in systole) than for the non-low blood pressure group (> 100mmHg in systole) (165 ± 106mg vs. 238 ± 124mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0mL vs. 137.7 ± 56.1mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3mL vs. 94.6 ± 55.7mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100mmHg.

Long-term impact of angiotensin receptor-neprilysin inhibitor based on short-term treatment response in heart failure.

The long-term effect of angiotensin receptor-neprilysin inhibitor (ARNI) remains uncertain in patients who have experienced improvements in left ventricular (LV) systolic function or significant LV reverse remodelling following a certain period of treatment. It is also unclear how ARNI performs in patients who have not shown these improvements. This study aimed to assess the impact of prolonged ARNI use compared with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with and without significant treatment response after 1year of heart failure (HF) treatment. The present study enrolled patients with HF with reduced ejection fraction (HFrEF) who were treated with either ARNI or ACEIs/ARBs within 1year of undergoing index echocardiography. After 1year of treatment, patients were reclassified into the following groups: (i) patients with HF with improved ejection fraction and persistent HFrEF and (ii) patients with and without LV reverse remodelling based on the follow-up echocardiography. The effect of ARNI versus that of ACEIs/ARBs in each group was assessed from the time of categorizing into new groups using the composite event of all-cause mortality and HF hospitalization. A total of 671 patients with HFrEF (age, 66.4±14.1years; males, 66.8%) were included, and 133 (19.8%) composite events of death and rehospitalization for HF were observed during the follow-up (median follow-up, 44 [interquartile range, 34-51] months). ARNI had a significantly lower event rate than ACEIs/ARBs in patients with HF with improved ejection fraction (7.0% vs. 30.4%, P=0.020) and those with persistent HFrEF (17.6% vs. 49.7%, P<0.001). Irrespective of whether patients exhibited LV reverse remodelling (15.8% vs. 31.1%, P=0.001) or not (15.0% vs. 54.9%, P<0.001), ARNIs were associated with a significantly lower event rate than ACEIs/ARBs. Regardless of significant treatment response measured by either LVEF or LV reverse remodelling after 1year of treatment, the extended utilization of ARNI demonstrated a more favourable prognosis than that of ACEIs/ARBs in patients with HFrEF.

The evolution of hemodynamic force parameters after cardiac resynchronization

Abstract Funding Acknowledgements Type of funding sources: None. Background A new mathematical model allows calculation of hemodynamic forces (HDF) from routine transthoracic echocardiographic images. In large cohorts, the evolution of HDF parameters in patients after onset of cardiac resynchronization therapy (CRT) has not been investigated. Purpose To compare HDF parameters at baseline versus six months follow-up after CRT implantation in patients with non-ischemic cardiomyopathy. Methods Patients with LV ejection fraction (LVEF) ≤35%, QRS duration ≥130 ms and left bundle branch block were included. In the complete heart cycle, the following HDF parameters were calculated: apical-basal strength (AB strength), lateral-septal strength (LS strength), the ratio of LS strength to AB strength (LS-AB ratio) and the dominant angle of HDF (angle) (Figure 1). In the systolic thrust, apical-basal impulse (AB impulse) and the angle were measured (Figure 1). The measurements are presented as percentages, normalized for left ventricular volume and adjusted for fluid density and gravity acceleration. The measurements were acquired at baseline and six months after CRT implantation. Results 196 patients were included (mean age 64 ± 11 years, 62% male). Clinical and echocardiographic characteristics were acquired, as well as HDF parameters at baseline and after six months (Table 1). After six months a significant improvement occurred in clinical parameters (New York Heart Association class, Quality of Life and 6-minute walking distance) with significant reverse LV remodeling (reduction in left ventricular and left atrial volumes with increased LVEF and global longitudinal strain). Moreover, a significant change in the magnitude of apical-basal force, represented in the AB strength and AB impulse and in the orientation of force, represented as the ratio and the angle of HDF were observed. Conclusion The evaluation of HDF parameters after CRT implantation shows an increase in magnitude of force and a change in orientation of force. This new tool provides insight in changes of fluid dynamics after CRT implantation and may contribute to better understand the benefit of CRT.

Feasibility of CMR Imaging during Biventricular Pacing: Comparison with Invasive Measurement as a Pathway towards a Novel Optimization Strategy.

This prospective pilot study assessed the feasibility of cardiovascular magnetic resonance (CMR) imaging during biventricular (BIV) pacing in patients with a CMR conditional cardiac resynchronization therapy defibrillator (CRT-D) and compared the results with invasive volume measurements. Ten CRT-D patients underwent CMR imaging prior to device implantation (baseline) and six weeks after device implantation, including CRT-on and CRT-off modes. Left ventricular (LV) function, volumes, and strain measurements of LV dyssynchrony and dyscoordination were assessed. Invasive pressure-volume measurements were performed, matching the CRT settings used during CMR. Post-implantation imaging enabled reliable cine assessment, but showed artefacts on late gadolinium enhancement images. After six weeks of CRT, significant reverse remodeling was observed, with a 22.7 ± 11% reduction in LV end-systolic volume during intrinsic rhythm (CRT-off). During CRT-on, the LV ejection fraction significantly improved from 27.4 ± 5.9% to 32.2 ± 8.7% (p < 0.01), and the strain assessment showed the abolition of the left bundle branch block contraction pattern. Invasively measured and CMR-assessed LV hemodynamics during BIV pacing were significantly associated. Post-CRT implantation CMR assessing acute LV pump function is feasible and provides important insights into the effects of BIV pacing on cardiac function and contraction patterns. LV assessment during CMR may constitute a future CRT optimization strategy.

Cardiac resynchronization therapy via left bundle branch area pacing and a dual-chamber ICD; a CROSS-LEFT substudy

Abstract Funding Acknowledgements Type of funding sources: None. Background Left bundle branch area pacing (LBBAP) has emerged as a promising technique to deliver cardiac resynchronization therapy (CRT). Purpose We sought to evaluate the feasibility of a single LBBAP lead connected to a dual-chamber ICD in patients indicated with a CRT-D implantation. Methods The CROSS-LEFT study prospectively included consecutive sinus rhythm patients with a reduced ejection fraction and a complete left bundle branch block. A DF-1 lead was implanted at the right ventricular apex, and an LBBAP lead through the interventricular septum. Patients were implanted with a dual-chamber DF-1 defibrillator (ICD) connected to the atrial lead (RA port), the LBBAP lead (RV IS-1 port), and the defibrillation lead (RV DF-1 port), the IS-1 pin being capped. Atrioventricular delay was optimized to ensure fusion between LBBAP and native conduction from the right bundle. Patients were followed during 6 months. Results A total of 22 patients were included (median age 68 years, 77% male, 41% ischemic). LBBAP resulted in a significant reduction of median QRS width from 161 to 128ms (p&amp;lt;0.0001). At 6 months, median ventricular sensing was 18mV (range 5–31, IQR 9), and LBBAP threshold 0.5V (range 0.25–0.75, IQR 0). Median LVEF significantly improved from 27 to 45% at 6 months (p&amp;lt;0.0001), with a median reduction of LV end-systolic volume of 32% (p=0.0002), 67% of patients being considered as super-responders. Conclusion In patients with a left bundle branch block indicated with a biventricular defibrillator, CRT can be safely and efficiently performed via a single LBBAP lead connected to a dual-chamber ICD, and is associated with significant electromechanical reverse remodeling.

P72 A CASE OF DRAMATIC HEART CHAMBERS REVERSE REMODELING AND DISEASE REGRESSION IN A PATIENT WITH HEART FAILURE AND END–STAGE RENAL FAILURE TREATED WITH SACUBITRIL/VALSARTAN AND SGLT2I: THE IMPORTANCE OF PUSHING THE BOUNDARIES

Abstract Background Heart failure (HF) therapy has been disrupted by the introduction of 2 new prognostic–relevant drugs: Sacubitril/Valsartan and SGLT2i. However, the amount of evidence for guideline–directed HF therapies in the context of chronic kidney disease (CKD) is relatively modest, especially in advanced stages (e.g., on haemodialysis). Aim of this report is to describe the feasibility and the efficacy of HF medical therapy in a patient with naive HFrEF and CKD on haemodialysis. Case report: A woman in her 40’s, with no cardiovascular history, affected by polycystic kidney disease end end–stage CKD placed on hemodialysis for the previous 9 months, underwent a echocardiography (TTE) in 09/2021, as part of investigations for kidney transplantation. The TTE showed a picture consistent with dilated cardiomyopathy with reduced EF, severe left atrium (LA) dilation and moderate–to–severe mitral regurgitation (MR). Thus, the patient was temporarily suspended from the transplant list. She was on chronic diuretic therapy with high dose of furosemide (250mg b.i.d.), with a residual diuresis of 400–500 mL per day. An elective coronary angiography showed normal coronary arteries. A Cardiac Magnetic Resonance (CMR) confirmed the diagnosis of DCM with severe dilation of the left ventricle (LV), reduced EF and severe MR. A cardiopulmonary exercise test (CPET) showed mild functional limitation with no pulmonary vascular limitation. After a multidisciplinary evaluation involving HF specialists and nephrologists, the recommended quadruple HF therapy was started and gradually up–titrated during the following 10 months. Neither the hemodialysis protocol nor the diuretic therapy was changed throughout this period. No adverse events were observed (e.g., increased sessions or dialysis schedule, hyperkalemia, hypotension). During this timeframe, the patients was asymptomatic and a progressive and sustained decrease in N–terminal pro B–type natriuretic peptide (NT–proBNP) from 26356 to 1556 ng/ml was observed. We documented a significant amelioration in CPET and other laboratory parameters (sST2), as well as a consistent reverse remodeling of the left heart chambers and a significant reduction in MR grade. Conclusions We described a case of significant left heart chambers reverse remodeling and disease regression in a patient with end–stage CKD presenting with HFrEF treated with off–label optimized HF medical therapy. Further studies on hemodialyzed HF patients will be needed.

Considering Diastolic Dyssynchrony as a Predictor of Favorable Response in LV-Only Fusion Pacing Cardiac Resynchronization Therapy

Background: CRT improves systolic and diastolic function, increasing cardiac output. Aim of the study: to assess the outcome of LV diastolic dyssynchrony in a population of fusion pacing CRT. Methods: Diastolic dyssynchrony was measured by offline speckle-tracking-derived TDI timing assessment of the simultaneity of E″ and A″ basal septal and lateral walls. New parameters introduced: E″ and, respectively, A″ time (E″T/A″T) as the time difference between E″ (respectively, A″) peak septal and lateral wall. Patients were divided into super-responders (SR), responders (R), and non-responders (NR). Results: Baseline characteristics: 62 pts (62 ± 11 y.o.) with idiopathic DCM, EF 27 ± 5.2%; 29% type III diastolic dysfunction (DD), 63% type II, 8% type I. Average follow-up 45 ± 19 months: LVEF 37 ± 7.9%, 34%SR, 61%R, 5%NR. The E″T decreased from 90 ± 20 ms to 25 ± 10 ms in SR with significant LV reverse remodeling (LV end-diastolic volume 193.7 ± 81 vs. 243.2 ± 82 mL at baseline, p < 0.0028) and lower LV filling pressures (E/E' 13.2 ± 4.6 vs. 11.4 ± 4.5, p = 0.0295). DD profile improved in 65% of R with a reduction in E/E' ratio (21 ± 9 vs. 14 ± 4 ms, p < 0.0001). Significant cut-off value calculated by ROC curve for LV diastolic dyssynchrony is E″T > 80 ms and A″T > 30 msec. Conclusions: The study identifies the cut-off values of diastolic dyssynchrony parameters as predictors of favorable outcomes in responders and super-responder patients with fusion CRT pacing. These findings may have important implications in patient selection and follow-up.

Abstract 11588: Multicenter Development and Validation of a Machine Learning Model to Predict Myocardial Recovery During LVAD Support: The UCAR Score

Introduction: Although significant cardiac reverse remodeling is a prerequisite for a left ventricular (LV) assist device (LVAD) patient to be considered for device weaning, multiple factors including patient goals, physician comfort, and center experience, weigh in on this complex decision. Existing predictive models defining recovery as device removal may under detect patients that could benefit from a targeted bridge to recovery strategy. We sought to derive and validate a predictive tool to identify patients prone to reverse remodel, independent of the complex decision of device explant. Methods: Heart failure patients (N=782) requiring LVAD were enrolled at the Utah Transplant Affiliated Hospitals (n=537) and 5 US programs (n=245). Baseline characteristics were recorded. The primary outcome was ‘responder’ incidence, defined as follow-up LV ejection fraction (LVEF) ≥40% and LV end-diastolic diameter (LVEDD) ≤6 cm within one year on LVAD support. Bootstrap imputation and lasso variable selection techniques were used to derive a predictive model which was then validated. A predictive calculator was developed and patients were classified into groups with varying potential for reverse remodeling. Results: Patients were predominantly white (84%), males (82%), aged 56±1 years. Overall, 14.8% patients were identified as responders. A subset of 10 pre-operative variables associated with reverse remodeling were included in the multivariate model achieving an optimism-corrected C-statistic of 0.75 (95% CI: 0.73-0.84) (Figure) . Conclusions: The UCAR calculator is a machine learning-based multicenter and validated risk tool, implementing routine pre-operative clinical data, effectively stratifying patients into groups with varying potential for reverse remodeling. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery.

Impact of percutaneous mitral valve clipping on right ventricular functions

Abstract Background Percutaneous mitral valve clipping (PMVC) is being used successfully in the management of severe functional mitral regurgitation (MR) in patients with high surgical risk. However, the impact of (PMVC) on right ventricular volumes and functions is not clear. Aim The aim of the present study was to assess the impact of (PMVC) (on both short and intermediate terms) on right ventricular (RV) volumes and functions using trans-thoracic echocardiography. Methods The study population included 37 patients with severe (MR), and congestive heart failurewho wereat high surgical risk. The mean age was 61±14 years, 9 (24.3%)were males. (PMVC) was successfully done for all patients.All had clinical and echocardiographic follow up at 6 and 12-months post (PMVC). Results MR showed significant improvement after (PMVC). MRwas less than grade II in 29 (78%)of patients at 6 months and persisted at 12 months (P=0.0001). Similarly, tricuspid regurgitation (TR) showed marked improvement. Severe (TR) was seen in 29 patients (78%) before), but decreased to 7 patients (18.9%) after (PMVC) (P=0.004). Left ventricular ejection fraction (LVEF) improved from 32.63±13.35% at base line to 36.31±13.28% at 6 months (P=0.003). This was maintained at 12 months (35.38±91%) Table 1 shows the changes in RV end diastolic volume (RVDV); RV end systolic volume (RVSV) RV ejection fraction (RVEF), Tricuspid annulus plane systolic excursion (TAPSE), RV longitudinal systolic function by tissue Doppler imaging (TDI) as well as peak systolic pulmonary artery pressure (PASP). Conclusion (PMVC) induced a significant reverse remodeling of RV by decreasing both (RVDV) and (RVSV). Moreover, it improved longitudinal RV systolic function as well as (RVEF). This was maintained up to one year follow up. Funding Acknowledgement Type of funding sources: None.

Clinical myocardial recovery in advanced heart failure with long term left ventricular assist device support.

Left ventricular assist-device (LVAD) implantation is a life-saving therapy for patients with advanced heart failure (HF). With chronic unloading and circulatory support, LVAD-supported hearts often show significant reverse remodeling at the structural, cellular and molecular level. However, translation of these changes into meaningful cardiac recovery allowing LVAD explant is lagging. Part of the reason for this discrepancy is lack of anticipation and hence promotion and evaluation for recovery post LVAD implant. There is additional uncertainty about the long-term course of HF following LVAD explant. In selected patients, however, guided by the etiology of HF, duration of disease and other clinical factors, significant functional improvement and LVAD explantation with long-term freedom from recurrent HF events has been demonstrated to be feasible in a reproducible manner. The identified predictors of myocardial recovery suggest that the elective therapeutic use of potentially less invasive VADs for reversal of HF earlier in the disease process is a future goal that warrants further investigation. Hence, it is prudent to develop and implement tools to predict HF reversibility prior to LVAD implant, optimize unloading-promoted recovery with guideline directed medical therapy and monitor for myocardial improvement. This review article summarizes the clinical aspects of myocardial recovery and together with its companion review article focused on the biological aspects of recovery, they aim to provide a useful framework for clinicians and investigators.

Reviewing the Modern Therapeutical Options and the Outcomes of Sacubitril/Valsartan in Heart Failure.

Sacubitril/valsartan (S/V) is a pharmaceutical strategy that increases natriuretic peptide levels by inhibiting neprilysin and regulating the renin-angiotensin-aldosterone pathway, blocking AT1 receptors. The data for this innovative medication are mainly based on the PARADIGM-HF study, which included heart failure with reduced ejection fraction (HFrEF)-diagnosed patients and indicated a major improvement in morbidity and mortality when S/V is administrated compared to enalapril. A large part of the observed favorable results is related to significant reverse cardiac remodeling confirmed in two prospective trials, PROVE-HF and EVALUATE-HF. Furthermore, according to a subgroup analysis from the PARAGON-HF research, S/V shows benefits in HFrEF and in many subjects having preserved ejection fraction (HFpEF), which indicated a decrease in HF hospitalizations among those with a left ventricular ejection fraction (LVEF) < 57%. This review examines the proven benefits of S/V and highlights continuing research in treating individuals with varied HF characteristics. The article analyses published data regarding both the safeness and efficacy of S/V in patients with HF, including decreases in mortality and hospitalization, increased quality of life, and reversible heart remodeling. These benefits led to the HF guidelines recommendations updating and inclusion of S/V combinations a key component of HFrEF treatment.

Dual-chamber ICD for left bundle branch area pacing: the cardiac resynchronization and arrhythmia sensing via the left bundle (cross-left) pilot study.

Left bundle branch area pacing (LBBAP) has emerged as a promising technique to deliver cardiac resynchronization therapy (CRT). However, safety and efficacy of ventricular arrhythmia sensing via the left bundle in implantable cardioverter-defibrillator (ICD) recipients remain unclear. We sought to evaluate the feasibility of a single LBBAP lead connected to a dual-chamber ICD in patients indicated with a CRT-D implantation. The CROSS-LEFT pilot study prospectively included 10 consecutive patients with a reduced ejection fraction and a complete left bundle branch block, indicated with a prophylactic CRT-D. A DF-1 lead was implanted at the right ventricular (RV) apex, and an LBBAP lead through the interventricular septum. Ventricular fibrillation was induced at implantation in both conventional (RV) and left bundle branch area sensing configurations. The latter was the final sensing configuration, and patients were implanted with a dual-chamber DF-1 ICD connected to the atrial lead (RA port), the LBBAP lead (RV IS-1 port), and the defibrillation lead (RV DF-1 port), the IS-1 pin being capped. Atrioventricular delay was optimized to ensure fusion between LBBAP and native conduction from the right bundle. Patients were followed during 6months. No difference between both configurations was observed regarding R-wave sensing in sinus rhythm (p = 0.22), ventricular fibrillation median interval detection (p = 1.00), or total induced episode duration (p = 0.78). LBBAP resulted in a significant reduction of median QRS width from 164 to 126ms (p = 0.002). Median ventricular sensing significantly improved from 9.7 at implantation to 18.8mV at 6months (p = 0.01). Median LVEF also significantly improved from 29 to 44% at 6months (p = 0.002). Ventricular arrhythmia sensing and defibrillation can be performed via a single LBBAP lead connected to a dual-chamber ICD, and is associated with significant electromechanical reverse remodeling. NCT05102227 In patients presenting with left bundle branch block and left ventricular systolic dysfunction, a left bundle branch area pacing lead connected to a DF-1 dual-chamber implantable cardioverter-defibrillator provides safe ventricular arrhythmia sensing and efficient electro-mechanical resynchronization.

Left Atrial Remodeling after Mitral Valve Repair for Primary Mitral Regurgitation: Evolution over Time and Prognostic Significance.

Left atrial (LA) dilatation is associated with worse outcomes in primary mitral regurgitation (MR). However, the effects of mitral valve repair on LA size and its prognostic implications are not well known. In the current study, LA volume index (LAVi) and LA reservoir strain (LASr) were evaluated immediately before and after surgery, and during long-term follow-up in 226 patients undergoing mitral valve repair for primary MR (age 62 ± 13 years, 66% male). Mean LAVi was reduced significantly after surgery and at long-term follow-up (from 56 ± 28 to 38 ± 21 to 32 ± 17 mL/m2; p < 0.001). LASr reduced significantly after surgery but increased again during the long-term (from 23.6 ± 9.4 to 11.5 ± 5.0 to 17.3 ± 7.5%; p < 0.001). Age, pre-operative LAVi, MR severity, and postoperative transmitral pressure gradient were associated with LA reverse remodeling by the long-term check-up. During a median follow-up of 72 (40–114) months, 43 (19%) patients died. Patients with LAVi ≥ 42 mL/m2 at long-term follow-up showed significant higher mortality rates compared to patients with LAVI < 42 mL/m2 (p < 0.001), even after adjusting for clinical covariates. In conclusion, significant LA reverse remodeling was observed both immediately and at long-term follow-up after mitral valve repair. LA dilatation at long term follow-up after surgery was still associated with all-cause mortality.

Invasive Hemodynamic Assessment and Procedural Success of Transcatheter Tricuspid Valve Repair-Important Factors for Right Ventricular Remodeling and Outcome.

IntroductionSevere tricuspid regurgitation (TR) is a common condition promoting right heart failure and is associated with a poor long-term prognosis. Transcatheter tricuspid valve repair (TTVR) emerged as a low-risk alternative to surgical repair techniques. However, patient selection remains controversial, particularly regarding the benefits of TTVR in patients with pulmonary hypertension (PH).AimWe aimed to investigate the impact of preprocedural invasive hemodynamic assessment and procedural success on right ventricular (RV) remodeling and outcome.MethodsAll patients undergoing TTVR with a TR reduction of ≥1 grade without precapillary or combined PH [mean pulmonary artery pressure (mPAP) ≥25 mmHg, mean pulmonary artery Wedge pressure ≤ 15 mmHg, pulmonary vascular resistance ≥3 Wood units] were assigned to the responder group. All patients with a TR reduction of ≥1 grade and precapillary or combined PH were classified as non-responders. Patients with a TR reduction ≥2 grade were directly classified as responders, and patients without TR reduction were directly assigned as non-responders.ResultsA total of 107 patients were enrolled, 75 were classified as responders and 32 as non-responders. We observed evidence of significant RV reverse remodeling in responders with a decrease in RV diameters (−2.9 mm, p = 0.001) at a mean follow-up of 229 days (±219 SD) after TTVR. RV function improved in responders [fractional area change (FAC) + 5.7%, p < 0.001, RV free wall strain +3.9%, p = 0.006], but interestingly further deteriorated in non-responders (FAC −4.5%, p = 0.003, RV free wall strain −3.9%, p = 0.007). Non-responders had more persistent symptoms than responders (NYHA ≥3, 72% vs. 11% at follow-up). Subsequently, non-response was associated with a poor long-term prognosis in terms of death, heart failure (HF) hospitalization, and re-intervention after 2 years (freedom of death, HF hospitalization, and reintervention at 2 years: 16% vs. 78%, log-rank: p < 0.001).ConclusionHemodynamic assessment before TTVR and procedural success are significant factors for patient prognosis. The hemodynamic profiling prior to intervention is an essential component in patient selection for TTVR. The window for edge-to-edge TTVR might be limited, but timely intervention is an important factor for a better outcome and successful right ventricular reverse remodeling.

Restrictive annuloplasty on remodeling and survival in patients with end-stage ischemic cardiomyopathy

ObjectivesTo elucidate the influence of concomitant restrictive mitral annuloplasty (RMA) on postoperative left ventricular (LV) reverse remodeling and survival in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG). MethodsThis study comprised 157 patients with ischemic cardiomyopathy (LV ejection fraction ≤40%) who underwent CABG and completed echocardiographic examination at 1 year after surgery, with 84 (54%) undergoing concomitant RMA for clinically relevant ischemic mitral regurgitation. The primary end point was postoperative reduction in LV end-systolic volume index (LVESVI). The secondary end point was overall survival. Median follow-up was 5.1 years. ResultsAt baseline, patients who underwent CABG with RMA had a larger LVESVI (83 ± 23 vs 75 ± 24 mm; P = .046). One-year postoperatively, CABG with RMA reduced the LVESVI more than did CABG alone (37% vs 21% from baseline; P < .001), yielding nearly identical postoperative LVESVI (53 ± 27 vs 61 ± 26 mm; P = .065). In multivariable logistic regression analysis, concomitant RMA was associated with significant LV reverse remodeling (odds ratio, 2.79; 95% CI, 1.34-5.78; P = .006). The prevalence in moderate or severe mitral regurgitation was not different between the groups (7% vs 10%; P = .58). Survival rates were similar between the groups (5 years, 78% vs 83%; P = .35). ConclusionsIn patients with ischemic cardiomyopathy undergoing CABG, concomitant RMA was associated with significant reduction in LVESVI. The influence of LV reverse remodeling on survival remains undetermined.

Impact of baseline left ventricular volume on left ventricular reverse remodeling after cardiac resynchronization therapy.

Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival. Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles). A total of 864 patients were included (mean age 66 ± 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m2), 272 (32%) in quintile 2 (65-95 mL/m2), 247 (29%) in quintile 3 (95-125 mL/m2), 151 (18%) in quintile 4 (125-155 mL/m2), and 93 (11%) in quintile 5 (>155 mL/m2). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all). Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation.