Echocardiographic strain imaging and progression of atrial fibrillation in low-risk individuals.

Systemic inflammation, especially of white blood cells (WBCs), is being increasingly accepted as a central mechanism underlying the pathogenesis and development of heart failure (HF). Few studies have assessed their effectiveness as accessible and cost-efficient biomarkers for the early detection of left ventricular dysfunction, as well as their potential predictive value in patients with coronary artery disease (CAD). To explore the correlation between WBC parameters and low left ventricular ejection fraction (LVEF) in HF patients and to evaluate its predictive potential. Two-hundred patients with angiographically proven CAD were enrolled in the study. Lymphocyte and neutrophil counts were measured in an automated analyzer. The number of neutrophils was divided by serum level of high density lipoprotein (HDL) to obtain the neutrophil-to-HDL ratio (NHR). Regression analysis was used to examine correlations, and receiver operating characteristic curve analysis was employed to identify predictive value of these hematological markers. WBC, neutrophils, lymphocytes, and NHR are significantly higher among HF patients with low LVEF. Regression analysis revealed a negative association between LVEF and WBC (r 2 = 0.007), neutrophils (r 2 = 0.019), lymphocytes (r 2 = 0.089), and the NHR (r 2 = 0.013). ROC analysis revealed that the AUC for WBC was 0.61, with a sensitivity of 72% and specificity of 60%, while neutrophils showed the same AUC (0.61) but with 56% sensitivity and 60% specificity. Lymphocytes showed a higher AUC of 0.68 (72% sensitivity, 60% specificity), while NHR had the lowest AUC at 0.59 (65% sensitivity, 52% specificity). These data indicate that parameters of WBCs, notably lymphocytes, neutrophils, and NHR, can act as useful biomarkers for detection of decreased LVEF in patients with HF. These findings suggest that neutrophils, lymphocytes, and NHR are not only routinely available and cost-effective markers but may also serve as early predictors of reduced LVEF in CAD patients, offering potential utility in clinical risk stratification and management. Further research is needed to validate these findings and explore their potential as clinical risk markers and therapeutic targets in CAD with HF.

There are limited data on mortality in patients with moderate mixed aortic valve disease (MAVD), defined as the combination of moderate aortic stenosis (AS) and moderate aortic regurgitation (AR). Consequently, current guidelines lack specific recommendations for aortic valve replacement (AVR) in this population. This study aims to compare survival between moderate MAVD and isolated severe AS or severe AR, and to evaluate the impact of symptoms or left ventricular ejection fraction (LVEF) < 50%, as current criteria for AVR in severe AS or AR. Overall, 1926 patients were included from four centers: 527 with moderate MAVD, 413 with severe AR, and 986 with severe AS. The primary endpoint was all-cause mortality. Over a median follow-up of 7.2 (interquartile range 3.4-11.3) years, 748 patients died. After adjusting for clinical and echocardiographic variables (including New York Heart Association [NYHA] class, LVEF < 50%, and AVR as time-dependent covariate), moderate MAVD patients showed 10-year survival similar to severe AS but worse than severe AR (62%, 55%, and 79%, respectively; P < .001). Symptomatic moderate MAVD patients showed adjusted mortality comparable to symptomatic severe AS, while asymptomatic moderate MAVD patients had adjusted mortality similar to severe AR (symptomatic and asymptomatic). Moderate MAVD patients with LVEF < 50% had adjusted mortality comparable to severe AS with LVEF < 50%, while those with LVEF ≥ 50% showed mortality similar to severe AR (regardless of left ventricular dysfunction). In moderate MAVD, the presence of symptoms or LVEF < 50% is associated with increased mortality, comparable to isolated severe AS under similar conditions. Therefore, patients with moderate MAVD should benefit from AVR in the presence of symptoms or left ventricular dysfunction.

Background: Late cardiotoxicity is a recognized complication in survivors of childhood cancer treated with potentially cardiotoxic agents, particularly anthracyclines. These therapies may cause progressive myocardial injury through mechanisms involving oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. Over time, this process can lead to ventricular remodeling, dilated cardiomyopathy, and heart failure. Advanced ventricular dilation frequently results in functional mitral and tricuspid regurgitation, further worsening hemodynamic burden and clinical outcomes. Case summary: We report the case of a 42-year-old man with a history of non-Hodgkin lymphoma diagnosed in childhood and treated with chemotherapy, without subsequent cardiologic follow-up. From the age of 29, he developed progressive heart failure symptoms. Transthoracic echocardiography revealed severe functional mitral regurgitation with mixed mechanism (Carpentier type I due to annular dilation and type IIIa due to leaflet restriction) and massive tricuspid regurgitation, associated with severe atrial dilation, grade III diastolic dysfunction, and pulmonary hypertension. Left ventricular systolic dysfunction was documented with an ejection fraction of 36% and markedly reduced global longitudinal strain (−11%), consistent with non-ischemic dilated cardiomyopathy. The patient underwent mitral valve replacement and tricuspid valve repair but developed intraoperative cardiac arrest and postoperative mixed shock. Persistent severe ventricular dysfunction (LVEF 26%, GLS −8%) and multiple complications were observed. Conclusion: This case highlights the importance of long-term cardiovascular surveillance in childhood cancer survivors and the role of strain imaging in detecting chemotherapy-related cardiomyopathy.

Heart failure (HF) is a prevalent cardiovascular condition among the elderly population, with an incidence rate that continues to rise annually, highlighting the urgent need for effective therapeutic interventions. Sustained activation of Toll-like receptor 4 (TLR4) may contribute to left ventricular dysfunction and adverse cardiac remodeling through the induction of myocardial inflammation and oxidative stress - pathological processes that closely align with the hallmark features of HF. Preclinical studies in animal models have demonstrated that TLR4 deficiency improves cardiac function in aged mice; however, the precise role and underlying mechanisms of TLR4 in human HF remain poorly understood. This study aims to test the central hypothesis that TLR4 serves as a critical molecular link between chronic inflammation and the pathophysiology of HF. HF was induced in 18-month-old male C57BL/6J mice via continuous subcutaneous infusion of isoproterenol (ISO, 30 mg/kg/day) over a period of 3 weeks. Thereafter, mice received daily intraperitoneal injections of the TLR4 inhibitor TAK-242 (2 mg/kg), deoxyribonuclease I (DNase I, 5 mg/kg), or the peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 (4 mg/kg) for 7 consecutive days. Cardiac function was assessed using a ultrasound imaging system. HE staining and Masson staining were employed to evaluate myocardial pathological changes and collagen deposition. ELISA was performed to measure serum levels of myeloperoxidase-DNA (MPO-DNA), neutrophil elastase-DNA (NE-DNA), cTnI, NT-proBNP, IL-1beta, IL-6 and TNF-alpha. Immunofluorescence staining was performed to detect the co-localization levels of Ly6G with myeloperoxidase (MPO) and citrullinated histone H3 (cit-H3) in myocardial tissue, in order to assess the formation level of neutrophil extracellular traps (NETs). Western blot were utilized to determine the expression level of TLR4 protein. The expression of TLR4 was significantly upregulated in the myocardial tissue of aged HF mice. Inhibition of TLR4 not only markedly improved cardiac function but also alleviated pathological damage to myocardial tissue and reduced collagen fiber deposition. Concurrently, it also decreased the serum levels of MPO-DNA, NE-DNA, NT-proBNP, cTnI, and inflammatory factors. Moreover, the colocalization levels of Ly6G with MPO or cit-H3 in myocardial tissue was also diminished. These findings were consistent with the effects observed following DNase I and GSK484 interventions. Targeting TLR4 can mitigate inflammatory responses and enhance cardiac function in HF mice by inhibiting NETs formation. Key words Heart failure " Cardiac function " Inflammation " Toll-like receptor 4 " Neutrophil extracellular traps.

In severe aortic stenosis with reduced left ventricular ejection fraction (LVEF), transcatheter aortic valve implantation (TAVI) improves systolic function. Self-expanding valves (SEV) show haemodynamic advantages over balloon-expandable valves (BEV), but whether this yields greater recovery of left ventricular function remains uncertain. To compare change in ejection fraction between BEV and SEV in adults with LVEF < 40% undergoing TAVI, and to assess haemodynamics and clinical outcomes at 30 days and 12 months. Observational cohort using a national registry of adults with LVEF < 40% and no prior myocardial infarction, coronary bypass, or more-than-moderate mitral regurgitation. Nearest-neighbor matching balanced annular perimeter, diameters, and calcification. Echocardiographic outcomes and major adverse cardiac and cerebrovascular events (MACCE) were assessed at 30 days and 12 months. Subgroup analyses stratified patients by annular perimeter ≤ 73.5 or > 73.5 mm. Of 922 patients, 574 received a BEV and 348 a SEV. Ejection fraction improved by 30 days and was maintained at 12 months, with no between-group difference. Haemodynamics favored SEV, with lower mean gradients at 30 days and 12 months (both p < 0.001). Clinical outcomes, including MACCE, were similar at 30 days and 12 months, and findings were consistent in small and large annulus strata. In patients with reduced LVEF, TAVI produced sustained improvement in ejection fraction irrespective of valve platform, and SEV conferred a haemodynamic advantage without differences in ejection fraction or clinical outcomes.

Aortic stenosis (AS) induces left ventricular diastolic dysfunction, which is associated with left atrial (LA) dysfunction. However, the prognostic impact of LA dysfunction in the surgical intervention for AS remains unclear. Among the 812 patients who underwent isolated surgical aortic valve replacement (SAVR) for AS at 8 institutions between 2016 and 2021, 366 with available preoperative left atrial volume index (LAVI) were included. Based on the optimal value of 40 mL/m2-derived from receiver operating characteristic curve analyses-patients were stratified into a LA enlargement group (n = 219) and a non-enlargement group (n = 147), and 5-year outcomes were investigated. Age (76.0 vs 76.0 years, P = .489) and sex (male 44.3% vs 50.3%, P = .256) were comparable, while the LA enlargement group showed lower estimated glomerular filtration rate (eGFR) (52.3 vs 59.2 mL/min/1.73 m2, P = .002), serum albumin (3.9 vs 4.0 g/dL, P = .003), and ejection fraction (65.0% vs 70.0%, P < .001), as well as a higher tendency for atrial fibrillation (20.1% vs 12.2%, P = .066), and higher Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) (3.10% vs 2.91%, P = .029). The 5-year incidence of cardiac mortality was higher in the LA enlargement group (13.4% vs 2.6%, P = .001). Multivariable analysis identified preoperative LA enlargement (LAVI ≥ 40 mL/m2) as an independent predictor of cardiac mortality (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.01-4.82; P = .041). Left atrial enlargement was also associated with higher all-cause mortality and heart failure readmission (17.4% vs 7.6%, P = .002; and 11.0% vs 2.8%, P = .013, respectively). In patients with severe AS undergoing isolated SAVR, a preoperative LAVI ≥ 40 mL/m2 was associated with midterm mortality and heart failure, suggesting that SAVR before significant LA enlargement may improve prognosis.

This study investigates mortality predictors in patients with NYHA Class III or IV heart failure and left ventricular systolic dysfunction at two Pakistani hospitals (n = 299). Survival rates declined over time, with no significant gender differences observed in anemic patients via Kaplan–Meier analysis. Cox proportional hazards and Bayesian Cox regression identified age, anemia, ejection fraction, hypertension, and serum creatinine as significant mortality predictors. Among parametric models, the exponential distribution demonstrated optimal fit based on Akaike and Bayesian information criteria. The analysis revealed that elevated serum sodium levels were associated with reduced mortality risk. Methodologically, this research provides a comprehensive multimethod comparison of survival analysis techniques within a Pakistani cohort, highlighting the Cox model's superior predictive performance while demonstrating the utility of parametric approaches when specific hazard forms are assumed. The consistent identification of key prognostic factors across multiple analytical methods strengthens the clinical relevance of these findings for risk stratification and targeted interventions in advanced heart failure patients within similar resource-limited settings.

Heart failure (HF) is a prevalent cardiovascular condition among the elderly population, with an incidence rate that continues to rise annually, highlighting the urgent need for effective therapeutic interventions. Sustained activation of Toll-like receptor 4 (TLR4) may contribute to left ventricular dysfunction and adverse cardiac remodeling through the induction of myocardial inflammation and oxidative stress – pathological processes that closely align with the hallmark features of HF. Preclinical studies in animal models have demonstrated that TLR4 deficiency improves cardiac function in aged mice; however, the precise role and underlying mechanisms of TLR4 in human HF remain poorly understood. This study aims to test the central hypothesis that TLR4 serves as a critical molecular link between chronic inflammation and the pathophysiology of HF. HF was induced in 18-month-old male C57BL/6J mice via continuous subcutaneous infusion of isoproterenol (ISO, 30 mg/kg/day) over a period of 3 weeks. Thereafter, mice received daily intraperitoneal injections of the TLR4 inhibitor TAK-242 (2 mg/kg), deoxyribonuclease I (DNase I, 5 mg/kg), or the peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 (4 mg/kg) for 7 consecutive days. Cardiac function was assessed using a ultrasound imaging system. HE staining and Masson staining were employed to evaluate myocardial pathological changes and collagen deposition. ELISA was performed to measure serum levels of myeloperoxidase-DNA (MPO-DNA), neutrophil elastase-DNA (NE-DNA), cTnI, NT-proBNP, IL-1β, IL-6 and TNF-α. Immunofluorescence staining was performed to detect the co-localization levels of Ly6G with myeloperoxidase (MPO) and citrullinated histone H3 (cit-H3) in myocardial tissue, in order to assess the formation level of neutrophil extracellular traps (NETs). Western blot were utilized to determine the expression level of TLR4 protein. The expression of TLR4 was significantly upregulated in the myocardial tissue of aged HF mice. Inhibition of TLR4 not only markedly improved cardiac function but also alleviated pathological damage to myocardial tissue and reduced collagen fiber deposition. Concurrently, it also decreased the serum levels of MPO-DNA, NE-DNA, NT-proBNP, cTnI, and inflammatory factors. Moreover, the colocalization levels of Ly6G with MPO or cit-H3 in myocardial tissue was also diminished. These findings were consistent with the effects observed following DNase I and GSK484 interventions. Targeting TLR4 can mitigate inflammatory responses and enhance cardiac function in HF mice by inhibiting NETs formation.

This study used two‑dimensional speckle‑tracking imaging (2D‑STI) and pressure‑strain loop (PSL) analysis to investigate the impact of peak strain dispersion (PSD) and septal flash (SF) on left ventricular myocardial work in patients with complete left bundle branch block (CLBBB). We enrolled 110 patients with CLBBB, stratified by the presence (n = 69) or absence (n = 41) of SF, and 45 matched controls. Two-dimensional speckle tracking imaging was employed to obtain the PSD (defined as the standard deviation of the time to peak longitudinal strain in all left ventricular segments). PSL analysis quantified global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global work index (GWI) and regional myocardial work parameters. The correlations of SF and PSD with work indices were assessed, and multivariate regression identified predictors of left ventricular systolic dysfunction (GWI < 1907 mmHg%). The SF group exhibited significantly higher PSD and GWW, and lower GWE, GWI, and GCW than the non-SF group (all p < 0.05). Both SF and higher PSD were negatively correlated with the work indices of the septum, free wall, and their ratios (all p < 0.01). Multivariate analysis confirmed that SF (OR: 2.717, 95% CI: 1.037-7.119) and PSD (OR: 1.055, 95% CI: 1.019-1.093) are independent risk factors for left ventricular systolic dysfunction. CLBBB patients with SF have greater left ventricular systolic impairment, coupled with septal-to-free wall workload imbalance. PSD, a global dyssynchrony parameter, complements the local visual index SF.

Managing pregnant patients in the coronary care unit and the intensive care unit has been a challenge for many clinicians, as they do not encounter those special populations on a routine basis. Peripartum cardiomyopathy (PPCM) is an uncommon but potentially life-threatening condition that occurs during the last month of pregnancy or within five months of delivery. It is associated with left ventricular systolic dysfunction, leading to reduced ejection fraction and heart failure. Although the exact etiology remains unclear, potential contributing factors can include factors such as myocarditis, abnormal immune responses, genetic predispositions, and hormonal imbalances. The future implications of PPCM are wide. Besides physical illness, mental illness can also limit functionality and impose health challenges. Additionally, subsequent pregnancies carry an increased risk of recurrence, especially if cardiac function remains poor. Ongoing research into the molecular and genetic underpinnings of PPCM may pave the way for different targeted therapies and strategies focusing on prevention. Increasing awareness, early detection, and advances in treatment can significantly reduce morbidity and mortality associated with PPCM. Multidisciplinary care is crucial in optimizing outcomes for women affected and their families. This mini review aims to help appraise healthcare providers and clinicians in addressing and managing this challenging condition.

Objective: Takotsubo syndrome (TTS) is an acute form of heart failure characterized by transient left ventricular systolic dysfunction. Given the complex cardiohepatic interactions observed in heart failure, this study aimed to evaluate the prognostic significance of hepatic T1 mapping in patients with TS. Materials and Methods: In this retrospective pilot study, cardiovascular magnetic resonance (CMR) including hepatic T1 mapping was performed in 66 consecutive patients with TTS (60 females; mean age 70.96 ± 10.11 years). The median duration of long-term follow-up was 7 months (interquartile range, 2-16 months). The primary endpoint was a composite of out-of-hospital all-cause mortality and major cardiovascular or cerebrovascular adverse events, including heart failure hospitalization, TTS recurrence, and ischemic stroke. Results: During the median follow-up period of 7 months, 12 (18%) patients experienced the primary endpoint. Kaplan-Meier analysis revealed a significantly lower event-free survival in patients with higher hepatic T1 values (log-rank, p = 0.001). In multivariable Cox regression analysis, hepatic T1 mapping emerged as an independent predictor of adverse outcomes (HR 1.010; 95% CI 1.002-1.017, p = 0.010). Conclusions: Elevated hepatic T1 mapping values were independently associated with an increased risk of adverse cardiovascular events during follow-up. Incorporating hepatic T1 mapping into the clinical evaluation of patients with TTS may improve risk stratification and support more personalized management strategies.

Rationale:Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an arrhythmogenic cardiomyopathy characterized by nonischemic left-ventricular scar, ventricular arrhythmias, and risk of sudden cardiac death. Diagnosis is often guided by cardiac magnetic resonance (CMR) and clinical criteria.Patient concerns:A 51-year-old man presented with 10 months of intermittent chest tightness and dyspnea, which worsened over 1 month, and 1 episode of syncope.Diagnoses:Transthoracic echocardiography showed severe left ventricular systolic dysfunction (left ventricular ejection fraction 19%). CMR demonstrated nonischemic subepicardial fibrosis and diffuse left ventricular free-wall thinning consistent with ALVC. Coronary angiography revealed no significant stenosis. A clinical cardiomyopathy panel test reported findings supportive of ALVC.Interventions:Guideline-directed medical therapy was initiated, and a cardiac resynchronization therapy defibrillator was implanted for left ventricular dysfunction with dyssynchrony and arrhythmic risk.Outcomes:Ten days after discharge, a localized device-pocket infection occurred and was managed with debridement, negative-pressure therapy, and intravenous vancomycin, with full recovery. At 3 and 6 months, left ventricular ejection fraction improved to 27% and 36%, respectively, and device interrogation documented no malignant ventricular arrhythmias.Lessons:This case underscores the diagnostic value of CMR and supports the combined strategy of cardiac resynchronization therapy defibrillator in left ventricular–dominant disease with dyssynchrony, aligning with contemporary guidelines.

Severe chronic degenerative mitral regurgitation (MR) is characterised by altered hemodynamics and high-shear stress, which initiate left ventricular (LV) remodelling, including upregulation of various cytokines. We evaluated endothelial activation during surgical correction of chronic MR by assessing adhesion molecules ICAM-1 and VCAM-1, classic markers of inflammation, and their association with postsurgical LV dysfunction (LVD). The study included asymptomatic patients with grade 3-4 degenerative MR. Transthoracic echocardiography data and blood samples were collected before and five days after surgical correction of MR. Circulating levels of adhesion molecules were measured by ELISA. Ejection fraction, end-diastolic diameter (EDD), and volume all decreased significantly after surgery. A significant decline in ICAM-1 concentration was observed between the two periods (457.11±256.12 vs. 240.29±157.14 ng/mL; p=0.031), whereas VCAM-1 levels did not change significantly. Leukocyte count and C-reactive protein were significantly higher in the postoperative period. Early postoperative LVD (in 35.7% of patients) was not correlated with adhesion molecule levels. However, we observed significant changes in ICAM-1 levels associated with postoperative EDD >5.6 cm, which indicates LV dilatation. These patients had markedly lower preoperative and postoperative ICAM-1 values than others. Serum ICAM-1 levels significantly decline following surgical correction of MR and are associated with postoperative enlargement of the LV. Our study highlights dynamic changes in endothelial activity and underscores the need for a better understanding of this process in MR.

We describe an unusual case involving a 25-year-old male who presented with breathlessness, cough, chest pain, abdominal pain, and significant weight loss. Detailed evaluation revealed pulmonary tuberculosis, an adrenal mass with biochemical evidence of a dual-secretory pheochromocytoma and severe dilated cardiomyopathy with profound left ventricular dysfunction. The coexistence of these conditions is extremely rare and highlights several clinical challenges - both in diagnosis and management. This case report emphasizes the importance of considering uncommon etiologies when confronted with multi-system involvement in young patients, the diagnostic difficulties posed by overlapping clinical features, and the critical role of a multidisciplinary approach in achieving optimal outcomes.

Left ventricular (LV) longitudinal function is a prognostic marker of hospitalization and mortality in LV dysfunction. Recently, left atrial (LA) reservoir and conduit strain have also been presented as independent prognostic markers. However, the atria and ventricles are coupled in the fibrous atrioventricular plane (LA-LV coupling). The degree to which the LA strain is affected, or even determined, by the LV longitudinal function in LV dysfunction has been explored by echocardiography, but not by cardiac magnetic resonance imaging (CMR). Therefore, we aimed to quantify the association between LV longitudinal ventricular function and LA strain using CMR feature-tracking. Three hundred and forty-two patients with LV dysfunction (including heart failure with reduced ejection fraction (HFrEF), candidates for cardiac resynchronization therapy (CRT) implantation, and ischaemic heart disease (IHD)), and 19 healthy controls (HC) who had undergone CMR were retrospectively included. LV global longitudinal strain (LV-GLS), LV atrioventricular plane displacement (AVPD), and LA-GLS (i.e. reservoir strain) were analysed in long-axis views using CMR feature-tracking. LA-GLS was lower in the LV dysfunction group when compared to HC (12 ± 8% vs 19 ± 7, P < .001), mirroring reductions in LV-GLS (-10 ± 5% vs -19 ± 3, P < .001), and LV-AVPD (9 ± 3 vs 15 ± 2 mm, P < .001). The coefficient of determination (r2) between LV-GLS and LA-GLS was .40 (95% CI 0.32-0.48) for the whole cohort, and 0.39 (95% CI 0.31-0.47) between LV-AVPD and LA-GLS. In a large cohort comprising both patients with LV dysfunction and HC, LA reservoir function quantified as LA-GLS was to a large extent determined by LV longitudinal function. LA function may not be an independent marker of global cardiac function for certain patient groups where diminished LA function can be a reflection of LV dysfunction.

Percutaneous autologous expanded CD34⁺ cell therapy (ProtheraCytes®) has demonstrated feasibility, manageable safety concerns and a regenerative potential in the EXCELLENT phase I/IIb trial (NCT02669810). Objective of our study was to assess HRQoL over 6 months following ProtheraCytes® therapy in patients with recent large AMI and left ventricular (LV) dysfunction. EXCELLENT was a multicenter, randomized, open-label, controlled phase I/IIb trial enrolling 77 AMI patients. Participants were randomized 3:1 to standard-of-care (SoC) plus transendocardial ProtheraCytes® injections or SoC alone. The per-protocol population included 49 subjects. Of those, 31 treated and 12 control patients were analyzable with complete baseline and follow-up 36-Item Short Form Survey (SF-36) data. HRQoL domains and composite scores were analyzed using repeated-measures ANCOVA adjusted for baseline values. At baseline, HRQoL was markedly impaired, consistent with severe LV dysfunction (mean physical functioning score at 63.3, LVEF 35.2%, elevated NT-proBNP). At 6 months, the treated group showed significant and sustained meaningful improvements in physical functioning (+ 16.6 PF, p = 0.0002), vitality (+ 12.7 VT, p = 0.0072), social functioning (+ 17.9 SF, p = 0.0059), and bodily pain (+ 17.0 BP, p = 0.0031). Between months 3 and 6, most HRQoL domains declined in controls but remained stable or improved in treated patients. In conclusion, ProtheraCytes® therapy was associated with significant HRQoL gains sustained over 6 months, alongside biological improvements. These findings support further evaluation of expanded CD34⁺ cell therapy to address the unmet need for durable functional recovery post-AMI.

Rate-dependent left bundle branch block (rdLBBB) is a unique clinical entity diagnosed in 0.5%-1% of the patients undergoing exercise testing. This study aimed to evaluate the electromechanical features in this acute and transient onset of left bundle branch block (LBBB) during exercise testing, and to assess its natural history. Fifty patients with rdLBBB were retrospectively analyzed. If a stress echocardiography was feasible, they were prospectively included for a supine bicycle echocardiography to evaluate electromechanical dyssynchrony. RdLBBB fulfills the criteria of LBBB in 95% of the patients. Sixty percent of the patients with rdLBBB progressed to a permanent LBBB within 3 years, with a lower heart rate at onset of rdLBBB and left ventricular ejection fraction (LVEF) as predictors. rdLBBB was characterized by acute mechanical dyssynchrony with septal flash (SF). Patients with lower baseline LVEF had more pronounced SF and a higher strain stage (p = 0.001). The electromechanical dyssynchrony was associated with more left ventricular dysfunction during exercise (p = 0.045). RdLBBB is a relative rare clinical entity, which is characterized by sudden onset and typical LBBB, fulfilling criteria of LBBB. The degree of dyssynchrony during rdLBBB seems to be determined by the baseline LVEF, with possible acute LV dysfunction during exercise.

Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21-1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97-1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10-0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83-1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04-0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15-0.73]). After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06398366.

Sympathetic activation plays a role in heart failure (HF) development. Afferent renal nerve input may induce sympathoexcitation via the hypothalamic paraventricular nucleus (PVN), which projects to the rostral ventrolateral medulla, a center for sympathetic regulation. Central dendritic release of vasopressin from PVN neurons reportedly stimulates neighboring presympathetic neurons, causing sympathoexcitation. This study investigated whether afferent renal nerves contribute to hypertensive cardiac dysfunction and whether the afferent renal nerve-PVN axis mediates sympathoexcitation via central vasopressin using salt-loaded Dahl salt-sensitive rats, a model of hypertensive HF. Salt loading began at 6 weeks of age, with selective afferent renal denervation and total renal denervation performed at 9 weeks in Dahl salt-sensitive rats. HF phenotypes were examined at 16 weeks, while sympathomodulation by afferent renal denervation was assessed at 12 weeks, the pre-HF phase. At 16 weeks, afferent renal denervation and total renal denervation similarly improved left ventricular systolic dysfunction, reduced myocardial fibrosis and related mRNA levels, and lowered plasma norepinephrine levels without reducing blood pressure in hypertensive rats. At 12 weeks, afferent renal denervation attenuated the increase in plasma norepinephrine and presympathetic neuron activity in the PVN and rostral ventrolateral medulla in hypertensive rats, while decreasing vasopressin-producing PVN neuron activity. In acute experiments, afferent renal nerve stimulation increased sympathetic outflow, but vasopressin V1a and V1b receptor blockade in the PVN suppressed this sympathoexcitation in hypertensive rats. Afferent renal nerve input activates the sympathetic nervous system before left ventricular systolic dysfunction and contributes to hypertensive HF, with PVN vasopressin driving this sympathoexcitation.