Improvement In Left Ventricular Ejection Fraction Research Articles

Impact of Early Invasive Strategy on Left Ventricular Function Recovery in Acute Myocardial Infarction Patients in Pakistan.

Background Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries like Pakistan, where healthcare resources are limited. Early Invasive Strategy (EIS), typically involving percutaneous coronary intervention (PCI), has been shown to improve outcomes in AMI patients. However, the effectiveness of EIS in resource-limited settings, such as Pakistan, remains under-explored. Objective This prospective observational cohort study aimed to assess the impact of an Early Invasive Strategy (EIS) on left ventricular (LV) function recovery in acute myocardial infarction (AMI) patients in Pakistan. The primary objective was to measure the change in left ventricular ejection fraction (LVEF) over six months. Secondary objectives included evaluating mortality, rehospitalization rates, and incidences of major adverse cardiovascular events (MACE). Multivariate regression analysis was employed to adjust for potential confounders. Methods The study was conducted from January to December 2023 at the National Institute of Cardiovascular Diseases (NICVD) satellite centers in Sukkur, Nawab Shah, and Khairpur. A total of 300 AMI patients presenting within 24 hours of symptom onset were included. Participants were divided into two groups: the EIS group (n = 150) received percutaneous coronary intervention (PCI) within 24 hours of admission, while the delayed treatment group (n = 150) received standard therapy, with invasive procedures performed after 24 hours if clinically indicated. Data were collected at baseline, during hospitalization, and at three- and six-months post-AMI. Results The EIS group demonstrated a significantly greater improvement in LVEF compared to the delayed treatment group (13.1% [95% CI, 10.8%-15.4%] vs. 7.5% [95% CI, 5.8%-9.2%], p < 0.001). Mortality was lower in the EIS group (3% [n = 4] vs. 9% [n = 13], p = 0.01), as were rehospitalizations for heart failure (7% [n = 10] vs. 14% [n = 21], p = 0.02) and incidences of MACE (8% [n = 12] vs. 16% [n = 24], p = 0.01). Multivariate regression analysis confirmed that EIS was independently associated with better LVEF improvement (coefficient = 5.78 [95% CI, 4.21-7.35], p < 0.001). Conclusion Early invasive treatments significantly enhance left ventricular function recovery and reduce mortality and rehospitalization rates in AMI patients in Pakistan. These findings advocate for the implementation of timely PCI interventions in resource-limited settings to improve clinical outcomes, particularly emphasizing cost-effectiveness and the availability of PCI.

Sex differences outcomes in conduction system pacing for patients with typical left bundle branch block

BackgroundBiventricular pacing (BVP) appears to confer more pronounced advantages in women, yet the impact of conduction system pacing (CSP) remains insufficiently characterized. This investigation seeks to elucidate sex-specific disparities in clinical outcomes among patients with typical left bundle branch block (LBBB) undergoing CSP, with a particular focus on assessing contributory factors. MethodsConsecutive patients diagnosed with nonischemic cardiomyopathy, exhibiting left ventricular ejection fraction (LVEF) ≤ 40%, and manifesting typical LBBB as Strauss criteria, underwent CSP. Subsequent longitudinal monitoring assessed improvements in LVEF and the composite endpoint of mortality or heart failure hospitalization (HFH). ResultsAmong the included 176 patients, women (n = 84, mean age: 69.5 ± 8.8 years) displayed smaller heart size (LVEDd, 62.0 ± 8.3 mm vs. 64.8 ± 7.9 mm, P = 0.023) and shorter baseline QRSd (163.5 ± 17.7 ms vs. 169.7 ± 15.1 ms; P = 0.013) than men. Of the 171 patients who completed the follow-up, super-response was observed in 120 (70%), with a higher occurrence in women than men (78.3% vs. 62.5%, P = 0.024). The incidence of death or HFH was numerically lower in women (7.1% Vs 13%, Log-rank P = 0.216). Notably, the super-response showed a significant difference in women compared to men at the same electrocardiography and/or echocardiographic parameters value. Mediation analysis between sex and super-response revealed that LVEDd and pQRSd play an intermediary role, with the mediation proportion of 26.07% and 27.98%, respectively. ConclusionsWomen may derive more benefits from CSP, and pQRSd and LVEDd partly drive this difference.

Left Ventricular Reverse Remodeling after Surgical Aortic Valve Replacement for Aortic Regurgitation-An Explorative Study.

The timing of treatment for chronic aortic valve regurgitation (AR), especially in asymptomatic patients, is gaining attention since less invasive strategies have become available. The aim of the present study was to evaluate left ventricular reverse remodeling after aortic valve replacement (AVR) for severe AR. Patients (n = 25) who underwent surgical AVR for severe AR with left ventricular ejection fraction (LVEF) less than 55% were included in this study. Preprocedural and follow-up clinical and echocardiographic measurements of LVEF and left ventricular (LV) diameters were retrospectively analyzed. Mean LVEF increased significantly following surgical AVR (p < 0.0001). LV diameters showed a clear regression (p = 0.0088). Younger patients and those receiving a mechanical valve tended to have less improved LVEF on follow-up than patients over 60 years or the ones who were implanted with a biological prosthesis (p = 0.0239 and p = 0.069, respectively). Gender had no effect on the degree of LVEF improvement (p = 0.4908). We demonstrated significant LV reverse remodeling following AVR for AR. However, more data are needed on LV functional and geometrical improvement comparing the different types of valve prostheses to provide an optimal treatment strategy.

The Pathobiology of Myocardial Recovery and Remission: From Animal Models to Clinical Observations in Heart Failure Patients.

Heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) is a morbid and life-threatening disease, arising secondary to abnormalities of cardiac structure and function that lead to adverse LV remodeling. Implementation of medical and device therapies results in significant improvements in patient outcomes that are associated with reverse LV remodeling and improved LV ejection fraction. This review provides an overview of the pathobiology of reverse LV remodeling in animal models and in HFrEF patients. We emphasize the differences between myocardial recovery and remission as well as the fragile nature of maintaining a state of myocardial remission.

Clinical outcomes of conduction system pacing compared to biventricular pacing in patients with mid-range ejection fraction.

There is a paucity of data comparing conduction system pacing (CSP) to biventricular pacing (BiVP) in patients with heart failure (HF) with mid-range left ventricular ejection fraction (LVEF). Compare the clinical outcomes of patients with mid-range LVEF undergoing CSP versus BiVP. Patients with mid-range LVEF (> 35 to 50%) undergoing CSP or BiVP were retrospectively identified. Lead performance, LVEF, HF hospitalization, and clinical composite outcome including upgrade to cardiac resynchronization therapy and mortality were compared. A total of 36 patients (20 BiVP, 16 CSP--14 His bundle pacing, 4 left bundle branch area pacing) were analyzed. The mean age was 73 ± 15, 44% were female, and the mean LVEF was 42 ± 5%. Procedural and fluoroscopy time was comparable between the two groups. QRS duration was significantly shorter for the CSP group compared to the BiVP group (P < 0.001). During a mean follow-up of 47 ± 36months, nosignificant differences were found in thresholds or need for generator change due to early battery depletion. LVEF improved in both groups (41.5 ± 4.5% to 53.9 ± 10.9% BiVP, P < 0.001; 41.6 ± 5.3% to 52.5 ± 8.3% CSP, P < 0.001). There were no significant differences in HF hospitalizations (P = 0.71) or clinical composite outcomes (P = 0.07). Among patients with HF with moderately reduced ejection fraction, CSP appears associated with similar improvements in LVEF and had similar clinical outcomes as BiVP in mid-term follow-up.

Protocol-driven approach to guideline-directed medical therapy optimization for heart failure: A real-world application to recovery

The objective of our study was to evaluate the real-world effects of an aggressive, personalized protocol for guideline-directed medical therapy (GDMT) titration in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We conducted a two-center retrospective cohort study. Patients with HFrEF who presented to a HF clinic from January 2020 to December 2022 were placed on a GDMT protocol. 180 patients were included in the study. Mean GDMT score significantly increased from 4.7 to 5.9 (p < 0.001) between initial and final visits. Mean left ventricular ejection fraction (LVEF) significantly increased from 28 % to 33 % (+5 %, p < 0.001). 27 (15.7 %) of the 172 patients with complete New York Heart Association (NYHA) classification data had improvement by at least 1 class, while 2 (1.2 %) patients had worsening NYHA classification. 140 (77.8 %) patients had no unplanned hospitalizations between visits. 21 (11.7 %) patients had an unplanned hospitalization for acute HF during the study period with a mean time from first clinic visit to hospitalization of 183 days (range: 13–821 days). 2 (1.1 %) patients were hospitalized due to GDMT-associated adverse drug events (i.e. hypotension, hyperkalemia). 7 (3.9 %) patients died during the study period, which was lower than the predicted 1-year death rate for our cohort (12.3 %) using the MAGGIC score. In conclusion, an aggressive, personalized protocol for GDMT titration in patients with HFrEF led to significant improvements in LVEF, NYHA classification, hospitalization, and mortality in a real-world setting. This protocol may help serve as a road map to lessen the gap between clinical knowledge and practice surrounding optimization of GDMT and move HFrEF patients toward a path to recovery.

Abstract We109: AAV9-Mediated Overexpression of Mixed Lineage Kinase 3 After Transaortic Constriction Improves Left Ventricular Function

Introduction: Mixed-lineage kinase 3 (MLK3) is a cGMP-dependent protein kinase 1α (PKG1α) substrate, preserving left ventricular (LV) function without affecting blood pressure (BP). MLK3 kinase-dependent effects maintain LV function, while kinase-independent signalling regulates BP. Thus, enhancing MLK3 kinase activity may improve LV function in heart failure (HF) while circumventing PKG1-induced hypotension. No MLK3-activation strategies exist currently, thus hindering progress in MLK3 research and potential therapeutics. Hypothesis: Augmenting MLK3 after pressure overload by transaortic constriction (TAC) would prevent LV hypertrophy and dysfunction in mice. Goal: To test the effect of adeno-associated virus 9 (AAV9)-mediated MLK3 overexpression on LV function, when administered in the setting of pre-existing LV hypertrophy and dysfunction. Methods: Male mice 12 weeks of age underwent 26G TAC or sham surgery. At day 5 post-TAC we administered by retro-orbital injection AAV9 encoding MLK3 or TdTomato negative control, each under control of the CM-specific cTNT promoter (AAV-MLK3: n=12 TAC, 7 sham; AAV-TdTomato: n=10 Tac, 8 sham. At day 28 post-AAV9 injection, we measured cardiac structure and function by echocardiography, invasive LV hemodynamics, and organ weights. Results: Echocardiography 5 days post-TAC confirmed TAC-induced LV hypertrophy and reduced systolic function prior to AAV9 treatment. At day 28, AAV-MLK3-treated TAC mice demonstrated improved LV ejection fraction and fractional shortening compared with TAC-AAV-Td controls, indicating improved systolic function. MLK3-treated TAC mice maintained higher LV systolic pressure post-TAC vs. Td controls, further indicating improved cardiac performance. Diastolic indices, including ratio of mitral E/A inflow velocities, tau, and LV relaxation rate were also improved in AAV-MLK3 TAC versus AAV-Td controls. AAV9-MLK3 administration had no effect on LV wall thickness or on LV or whole heart mass normalized to tibia length. MLK3 expression was increased 3-fold in AAV9-MLK3 TAC LVs compared with AAV9-Td controls. Conclusion: AAV9-mediated MLK3 overexpression after the onset of LV hypertrophy and dysfunction improves LV function in mice.

Efficacy of early administration of sacubitril/valsartan after coronary artery revascularization in patients with acute myocardial infarction complicated by moderate-to-severe mitral regurgitation: a randomized controlled trial.

Effects of angiotensin receptor/neprilysin inhibitors (ARNI) on ventricular remodeling in patients with heart failure, especially heart failure with reduced ejection fraction (HFrEF), are better than those of angiotensin-converting enzyme inhibitors (ACEI). Acute myocardial infarction (AMI) complicated by mitral regurgitation exacerbates ventricular remodeling and increases the risk of heart failure. There is limited evidence on the effects of early administration of ARNI in patients with AMI complicated by mitral regurgitation. The aim of this trial was to examine the effectiveness and the safety of early administration of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation. This was a randomized, single-blind, parallel-group, controlled trial. From June 2021 to June 2022, we enrolled 142 consecutive patients with AMI complicated by moderate-to-severe mitral regurgitation and followed them for 12months. The patients received standard treatment for AMI and were randomly assigned to receive ARNI or benazepril. The primary efficacy end points were the differences in mitral regurgitant jet area (MRJA), mitral regurgitant volume (MRV), concentration of n-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume and end-systolic volume (LVEDV and LVESV) between groups and within groups at baseline, 1, 3, 6, and 12months. Secondary end points included the rates of heart failure hospitalization, all-cause mortality, refractory angina, malignant arrhythmias, recurrent myocardial infarction, and stroke. Safety end points included the rates of hyperkalemia, renal dysfunction, hypotension, angioedema, and cough. The ARNI group had significantly lower NT-proBNP levels than the benazepril group at 1month and later (P < 0.001). MRJA and MRV significantly improved in the ARNI group compared with the benazepril group at 12months (MRJA: - 3.21 ± 2.18 cm2 vs. - 1.83 ± 2.81 cm2, P < 0.05; MRV: - 27.22 ± 15.22mL vs. - 13.67 ± 21.02mL, P < 0.001). The ARNI group also showed significant reductions in LVEDV and LVESV (P < 0.05) and improvement in LVEF (P < 0.05). Secondary end point analysis showed a significantly higher rate of heart failure hospitalization in the benazepril group compared with the ARNI group (HR = 2.03, 95% CI 1.12-3.68, P = 0.021). Safety end point analysis showed a higher rate of hypotension in the ARNI group (P < 0.05). Early use of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation can significantly reduce mitral regurgitation, improve ventricular remodeling, and decrease heart failure hospitalization. Nevertheless, caution is needed to avoid hypotension. Chinese Clinical Trial Registry (ChiCTR2100054255) registered on December 11, 2021.

Predictors and Prognostic Factors of Heart Failure with Improved Ejection Fraction.

Heart failure with reduced ejection fraction (HFrEF) patients who have improved ejection fraction have a better prognosis than those with persistently reduced ejection fraction. This study aimed to analyze the predictors for progression of patients with HFrEF to heart failure with improved ejection fraction (HFimpEF), as well as their characteristics and analyze predictors for prognosis. A retrospective analysis was conducted on 1251 patients with HFrEF at baseline, who also had a second echocardiogram 3 months. After left ventricular ejection fraction (LVEF) reassessment, patients were separated into the HFimpEF group (n = 408) and the persistent HFrEF group (n = 611). The primary endpoint was a composite of cardiovascular death or heart failure hospitalization. Multivariate logistic regression showed that without history of alcohol consumption (OR: 0.47, 95% CI: 0.28-0.78), non-New York Heart Association (NYHA) class III-IV (OR: 0.28, 95% CI: 0.15-0.52), without dilated cardiomyopathy (OR: 0.47, 95% CI: 0.26-0.84), concomitant hypertension (OR: 1.53, 95% CI: 1.02-2.29), -blockers use (OR: 2.29, 95% CI: 1.54-3.43), and lower uric acid (OR: 0.999, 95% CI: 0.997-1.000) could predict LVEF improvement. Kaplan-Meier curves demonstrated that HFimpEF patients had a significantly lower incidence of adverse events than HFrEF patients (log Rank p 0.001). Multivariate Cox regression found that older age (HR: 1.04, 95% CI: 1.02-1.06), NYHA class III-IV (HR: 2.25, 95% CI: 1.28-3.95), concomitant valvular heart disease (HR: 1.98, 95% CI: 1.01-3.85), and higher creatinine (HR: 1.003, 95% CI: 1.001-1.004) were independent risk factors for the primary endpoint in HFimpEF patients. HFrEF patients without a history of alcohol consumption, non-NYHA class III-IV, without dilated cardiomyopathy, concomitant hypertension, -blockers use, and lower uric acid were more likely to have LVEF improvement. Although the prognosis of HFimpEF patients was better than that of HFrEF patients, older age, NYHA class III-IV, concomitant valvular heart disease, and higher creatinine were still risk factors for cardiovascular events in HFimpEF patients.

Efficacy of Beta-Blockers and Angiotensin-Converting Enzyme Inhibitors in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis.

Non-ischemic dilated cardiomyopathy (NIDCM) is a form of heart failure with a poor prognosis and unclear optimal management. The aim of the study was to systematically review the literature and assess the efficacy and safety of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors in the management of chronic heart failure secondary to NIDCM and explore their putative mechanisms of action. Studies from 1990 to 2023 were reviewed using PubMed and EMBASE, focusing on their effects on left ventricular ejection fraction (LVEF) in NIDCM patients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Beta-blockers showed a significant beneficial effect on LVEF improvement in NIDCM, with an overall effect size of Cohen's d = 1.30, 95% confidence interval (CI) (0.76, 1.84), high heterogeneity (Tau2 = 0.90; Chi2 = 162.05, df = 13, P < 0.00001; I2 = 92%), and a significant overall effect (Z = 4.72, P < 0.00001). ACE inhibitors also showed a beneficial role, but with less heterogeneity (Tau2 = 0.02; Chi2 = 1.09, df = 1, P = 0.30; I2 = 8%) and a nonsignificant overall effect (Z = 1.36, P = 0.17), 95% CI (-0.24, 1.31). The study highlights the efficacy of carvedilol in improving LVEF in NIDCM patients over ACE inhibitors, recommends beta-blockers as first-line therapy, and advocates further research on ACE inhibitors.

Predicting factors for omitting beta-blockers in patients with tachycardia-induced cardiomyopathy after successful catheter ablation for atrial fibrillation.

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation.

Conduction system pacing upgrade versus biventricular pacing on pacemaker-induced cardiomyopathy: a retrospective observational study.

Objective: The feasibility of the conduction system pacing (CSP) upgrade as an alternative modality to the traditional biventricular pacing (BiVP) upgrade in patients with pacemaker-induced cardiomyopathy (PICM) remains uncertain. This study sought to compare two modalities of CSP (His bundle pacing (HBP) and left bundle branch pacing (LBBP)) with BiVP and no upgrades in patients with pacing-induced cardiomyopathy. Methods: This retrospective analysis comprised consecutive patients who underwent either BiVP or CSP upgrade for PICM at the cardiac department from 2017 to 2021. Patients with a follow-up period exceeding 12months were considered for the final analysis. Results: The final group of patients who underwent upgrades included 48 individuals: 11 with BiVP upgrades, 24 with HBP upgrades, and 13 with LBBP upgrades. Compared to the baseline data, there were significant improvements in cardiac performance at the last follow-up. After the upgrade, the QRS duration (127.81 ± 31.89 vs 177.08 ± 34.35ms, p < 0.001), NYHA class (2.28 ± 0.70 vs 3.04 ± 0.54, p < 0.05), left ventricular end-diastolic diameter (LVEDD) (54.08 ± 4.80 vs 57.50 ± 4.85mm, p < 0.05), and left ventricular ejection fraction (LVEF) (44.46% ± 6.39% vs 33.15% ± 5.25%, p < 0.001) were improved. There was a noticeable improvement in LVEF in the CSP group (32.15% ± 3.22% vs 44.95% ± 3.99% (p < 0.001)) and the BiVP group (33.90% ± 3.09% vs 40.83% ± 2.99% (p < 0.001)). The changes in QRS duration were more evident in CSP than in BiVP (56.65 ± 11.71 vs 34.67 ± 13.32, p < 0.001). Similarly, the changes in LVEF (12.8 ± 3.66 vs 6.93 ± 3.04, p < 0.001) and LVEDD (5.80 ± 1.71 vs 3.16 ± 1.35, p < 0.001) were greater in CSP than in BiVP. The changes in LVEDD (p = 0.549) and LVEF (p = 0.570) were similar in the LBBP and HBP groups. The threshold in LBBP was also lower than that in HBP (1.01 ± 0.43 vs 1.33 ± 0.32V, p = 0.019). Conclusion: The improvement of clinical outcomes in CSP was more significant than in BiVP. CSP may be an alternative therapy to CRT for patients with PICM. LBBP would be a better choice than HBP due to its lower thresholds.

Left bundle branch block cardiomyopathy (LBBB-CMP): from the not-so-benign finding of idiopathic LBBB to LBBB-CMP diagnosis and treatment.

two main objectives: (1) to explore the natural history of "asymptomatic" iLBBB carriers; (2) to characterize the outcomes and therapeutic approach used in a "real-world" cohort of possible LBBB-CMP patients (pts). tertiary care centre retrospective study of pts with iLBBB and possible LBBB-CMP, screened from a large hospital electrocardiographic database from 2011 to 2017 (LBBB = 347). To assign the 1st objective, only pts with left ventricular ejection fraction (LVEF) ≥ 50% and available follow-up (FU) data were included (n = 152). Regarding the 2nd objective, possible LBBB-CMP pts were selected and defined as iLBBB pts with LVD (LVEF < 50%) and no secondary causes for LVD (n = 53). Data were based on pts' careful review of medical records. focusing our 1st objective, 152 iLBBB carriers were identified. Median FU time were 8years, and 61% were female. During FU, approximately 25% developed LVD, 20% needed ≥ 1 cardiovascular (CV) hospitalization, and 15% needed a cardiac device implantation. The majority (2/3) of pts with LVD on FU (n = 35) had no secondary causes for LVD, being classified as possible LBBB-CMP pts. Time-to-LVD analysis showed no differences between pts with a known cause for LVD vs LBBB-CMP pts (Log-rank = 0.713). Concerning the 2nd objective, 53 possible LBBB-CMP pts were identified. Median FU time were 10years, and 51% were female. During the FU, 77% presented heart failure (HF) symptoms, and 42% needed ≥ 1 CV hospitalization, mainly due to HF. Half presented severe LVD at some point in time, and 55% needed a cardiac device, most of them a cardiac resynchronization therapy (CRT) device. Comparing CRT with non-CRT pts, no differences were found in terms of medical therapy, but better outcomes were observed in CRT group: LVEF improvement was higher (median LVEF improvement of 11% in non-CRT vs 27% in CRT; p < 0.001), and fully recovery from LVD was more frequent (50% of CRT vs 14% non-CRT; p = 0.028). our data strengthen current evidence on natural history of iLBBB, showing significant CV morbidity associated with the presence of iLBBB, and reinforces the need for a serial and proper FU of these carriers. Our data on "real-world" possible LBBB-CMP pts shows high rates of CV events, namely HF-related events, and supports the growing evidence pointing out CRT as this subgroup of pts' cornerstone of treatment. In conclusion, our work sheds additional light on these largely unknown topics and underlines the urgent need for larger and prospective studies addressing the identification of LVD development predictors in iLBBB carriers, as well as the establishment of diagnostic criteria and therapeutic approach for LBBB-CMP.

Echocardiographic Predictors of Improvement of Left Ventricular Ejection Fraction below 35% in Patients with ST-Segment Elevation Myocardial Infarction.

Introduction: An ST-elevation myocardial infarction (STEMI) is a clinical syndrome defined by symptoms of myocardial ischemia, persistent electrocardiographic ST-segment elevation and subsequent release of biomarkers suggestive of myocardial necrosis. In clinical practice, echocardiography has become essential in evaluating patients after acute myocardial infarction. We aimed to assess clinical and echocardiographic parameters that may affect LV function recovery in patients after STEMI. Methods: This study is a retrospective observational study from a tertiary referral center in Israel. We collected patients that were admitted with STEMI and a left ventricular ejection fraction (LVEF) below 35% on preliminary echocardiography at the index hospitalization and compared the findings to a follow-up study performed within 1-6 months after that event, in order to see if there are predictors of LVEF change > 10% within 90 days following STEMI. Results: This study included 101 patients that were admitted between 2016 and 2021. Within a median follow-up of 9.7 weeks (IQR 5.9-17.1), 27 (25.2%) patients had improved their LVEF, and 74 (69.2%) had no change or further reduced LVEF. Compared to patients without LVEF improvement, those with improved LVEF were more likely to be female (29.6% vs. 9.5%, p = 0.01), less likely to suffer from hypertension (33.3% vs. 56.8%, p = 0.04) and had marginally higher rates of thrombolysis treatment (14.1% vs. 4.1%, p = 0.06). Conclusions: in the population of STEMI patients with residual LVEF < 35%, approximately a quarter will improve at least 10% in their follow-up LVEF, and there were no clear echocardiographic predictors for this improvement.

Comparative effectiveness of mesenchymal stem cell versus bone-marrow mononuclear cell transplantation in heart failure: a meta-analysis of randomized controlled trials

BackgroundThere is no clear evidence on the comparative effectiveness of bone-marrow mononuclear cell (BMMNC) vs. mesenchymal stromal cell (MSC) stem cell therapy in patients with chronic heart failure (HF).MethodsUsing a systematic approach, eligible randomized controlled trials (RCTs) of stem cell therapy (BMMNCs or MSCs) in patients with HF were retrieved to perform a meta-analysis on clinical outcomes (major adverse cardiovascular events (MACE), hospitalization for HF, and mortality) and echocardiographic indices (including left ventricular ejection fraction (LVEF)) were performed using the random-effects model. A risk ratio (RR) or mean difference (MD) with corresponding 95% confidence interval (CI) were pooled based on the type of the outcome and subgroup analysis was performed to evaluate the potential differences between the types of cells.ResultsThe analysis included a total of 36 RCTs (1549 HF patients receiving stem cells and 1252 patients in the control group). Transplantation of both types of cells in patients with HF resulted in a significant improvement in LVEF (BMMNCs: MD (95% CI) = 3.05 (1.11; 4.99) and MSCs: MD (95% CI) = 2.82 (1.19; 4.45), between-subgroup p = 0.86). Stem cell therapy did not lead to a significant change in the risk of MACE (MD (95% CI) = 0.83 (0.67; 1.06), BMMNCs: RR (95% CI) = 0.59 (0.31; 1.13) and MSCs: RR (95% CI) = 0.91 (0.70; 1.19), between-subgroup p = 0.12). There was a marginally decreased risk of all-cause death (MD (95% CI) = 0.82 (0.68; 0.99)) and rehospitalization (MD (95% CI) = 0.77 (0.61; 0.98)) with no difference among the cell types (p > 0.05).ConclusionBoth types of stem cells are effective in improving LVEF in patients with heart failure without any noticeable difference between the cells. Transplantation of the stem cells could not decrease the risk of major adverse cardiovascular events compared with controls. Future trials should primarily focus on the impact of stem cell transplantation on clinical outcomes of HF patients to verify or refute the findings of this study.

Catheter ablation for atrial fibrillation and impact on clinical outcomes.

Catheter ablation is the most effective rhythm-control option in patients with atrial fibrillation (AF) and is currently considered an option mainly for improving symptoms. We aimed to assess the impact of catheter ablation on hard clinical outcomes. We performed a systematic review of randomized controlled trials (RCTs) comparing catheter ablation vs. optimized medical treatment. We searched MEDLINE, EMBASE, and CENTRAL on 8 January 2024, for trials published ≤10 years. We pooled data through risk ratio (RR) and mean differences (MDs), with 95% confidence interval (CI), and calculated the number needed to treat (NNT). Sub-group and sensitivity analyses were performed for the presence/absence of heart failure (HF), paroxysmal/persistent AF, early ablation, higher/lower quality, and published ≤5 vs. >5 years. Twenty-two RCTs were identified, including 6400 patients followed for 6-52 months. All primary endpoints were significantly reduced by catheter ablation vs. medical management: all-cause hospitalization (RR = 0.57, 95% CI 0.39-0.85, P = 0.006), AF relapse (RR = 0.48, 95% CI 0.39-0.58, P < 0.00001), and all-cause mortality (RR = 0.69, 95% CI 0.56-0.86, P = 0.0007, NNT = 44.7, driven by trials with HF patients). A benefit was also demonstrated for all secondary endpoints: cardiovascular mortality (RR = 0.55, 95% CI 0.34-0.87), cardiovascular (RR = 0.83, 95% CI 0.71-0.96), and HF hospitalizations (RR = 0.71, 95% CI 0.56-0.89), AF burden (MD = 20.6%, 95% CI 5.6-35.5), left ventricular ejection fraction (LVEF) recovery (MD = 5.7%, 95% CI 3.5-7.9), and quality of life (MLHFQ, AFEQT, and SF-36 scales). Catheter ablation significantly reduced hospitalizations, AF burden, and relapse, and improved quality of life. An impact on hard clinical outcomes, with an important mortality reduction and improvement in LVEF, was seen for patients with AF and HF.

Predictive value of early-phase heart rate reduction for subsequent recovery of left ventricular systolic function in heart failure with reduced ejection fraction.

Predictors of heart failure with recovered ejection fraction (HFrecEF) remain to be fully elucidated. This study investigated the impact of heart rate and its change on the recovery of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). From 398 outpatients who had a history of hospitalisation for heart failure, 138 subjects diagnosed as HFrEF (LVEF < 40%) on heart failure hospitalisation were enrolled and longitudinally surveyed. During follow-up periods more than one year, 64 and 46 patients were identified as HFrecEF (improved LVEF to ≥ 40% and its increase of ≥ 10 points) and persistent HFrEF, respectively. In the overall subjects, the reduction of heart rate through the observation periods was closely correlated with the improvement of LVEF (r = -0.508, p < 0.001). Heart rate on hospital admission for heart failure was markedly higher in patients with HFrecEF (112 ± 26 bpm) than in those with persistent HFrEF (90±18 bpm). Whereas heart rate at the first outpatient visit after discharge was already lower in the HFrecEF group (80 ± 13 vs. 85 ± 13 bpm in the persistent HFrEF group). A multivariate logistic regression analysis revealed that the decrease in heart rate from admission to the first visit after discharge was a significant determinant of HFrecEF (p < 0.001), independently of confounding factors such as ischemic heart disease and baseline LVEF and left ventricular dimension. Our findings suggest that heart rate reduction in the early phase after heart failure onset is a powerful independent predictor of the subsequent recovery of LVEF in HFrEF patients.

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients.

Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e., stemness, viability, phenotypes, paracrine activity, etc., need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention. To investigate the effect of RoD of MSCs on safety and efficacy in HF patients. RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints. Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001). Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Single-center experience of efficacy and safety of atrioventricular node ablation after left bundle branch area pacing for the management of atrial fibrillation.

Atrioventricular node ablation (AVNA) with permanent pacing is an effective treatment of symptomatic atrial fibrillation (AF). Left bundle branch area pacing (LBBAP) prevents cardiac dyssynchrony associated with right ventricular pacing and could prevent worsening of heart failure (HF). In this retrospective monocentric study, all patients who received AVNA procedure with LBBAP were consecutively included. AVNA procedure data, electrical and echocardiographic parameters at 6 months, and clinical outcomes at 1 year were studied and compared to a matched cohort of patients who received AVNA procedure with conventional pacing between 2010 and 2023. Seventy-five AVNA procedures associated with LBBAP were studied. AVNA in this context was feasible, with a success rate of 98.7% at first ablation, and safe without any complications. There was no threshold rise at follow-up. At 1 year, 6 (8%) patients were hospitalized for HF and 2 (2.7%) were deceased. Patients had a significant improvement in NYHA class and left ventricular ejection fraction (LVEF) (P ≤ 0.0001). When compared to a matched cohort of patients with AVNA and conventional pacing, AVNA data and pacing complications rates were similar. Patients with LBBAP had a better improvement of LVEF (+5.27 ± 9.62% vs. -0.48 ± 14%, P = 0.01), and a lower 1-year rate of composite outcome of hospitalization for HF or death (HR 0.39, 95% CI: 0.16-0.95, P = 0.037), significant on survival analysis (log-rank P-value = 0.03). AVNA with LBBAP in patients with symptomatic AF is feasible, safe, and efficient. Hospitalization for HF or death rate was significantly lower and LVEF improvement was greater.

Prognostic Impact of Left Ventricular Ejection Fraction Improvement after Transcatheter Aortic Valve Replacement.

Introduction: Transcatheter aortic valve replacement (TAVR) has become an efficient and safe alternative to surgical aortic valve replacement (SAVR). While severe aortic stenosis as well as severe aortic regurgitation (AR) are known to negatively impact left ventricular ejection fraction (LVEF), prior studies have shown that TAVR can lead to an improvement in LVEF. Thus far, little is known about the prognostic implication of LVEF improvement as a sole predictor of outcomes. Therefore, the aim of this study was to assess the prognostic impact of LVEF impairment before TAVR, as well as early LVEF improvement in patients undergoing TAVR. Materials and Methods: Patients undergoing TAVR in a large tertiary university hospital were consecutively included in a prospective registry. Transthoracic echocardiography (TTE) was performed at baseline, after 1 month and annually thereafter. Significant LVEF improvement was defined as a relative increase of ≥10% in LVEF at 30 days compared to baseline LVEF. The primary outcome was all-cause mortality at 1 year. Secondary outcomes were major adverse cardiovascular events (MACEs) including cardiovascular death, non-fatal myocardial infarction, stroke, bleeding and unplanned re-interventions of the aortic valve at 5 years. Results: Among 1655 patients who underwent TAVR between September 2011 and April 2024, the LVEF at baseline was available for 1556 patients. Of these, 1031 patients (66.2%) had preserved LVEF at baseline (LVEF ≥ 53%), whereas 303 patients (19.5%) had moderately reduced LVEF (40-52%) and 222 patients (14.3%) had severely reduced LVEF (<40%). Out of the patients with impaired LVEF, 155 (40.4%) patients showed a significant improvement in LVEF ≥10% after 30 days, while 229 (60.6%) patients showed no significant LVEF improvement (<10%). Patients with preserved LVEF at baseline had significantly better mortality outcomes than those with severely reduced LVEF (p < 0.001). LVEF improvement was associated with a survival benefit after 1 year (p = 0.009, HR 2.68, 0.95 CI 1.23-5.85) which diminished after 5 years (p = 0.058), but patients with LVEF improvement showed lower MACE rates at 5 years (p < 0.001). Conclusions: Preserved LVEF before TAVR is an independent predictor for improved outcomes. Additionally, early improvement in LVEF is associated with beneficial outcomes in patients undergoing TAVR.