Preserved Left Ventricular Ejection Fraction Research Articles

Outcomes of Watchful Waiting Strategy and Predictors of Postoperative Prognosis in Asymptomatic or Equivocally Symptomatic Chronic Severe Aortic Regurgitation With Preserved Left Ventricular Function.

The optimal surgical timing for asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction remains controversial. Two hundred ten consecutive patients (median age 65 years) with asymptomatic or equivocally symptomatic chronic severe aortic regurgitation and left ventricular ejection fraction ≥50% were registered. First, the treatment plans (aortic valve replacement or watchful waiting) after initial diagnosis were investigated. Then, 2 studies were set: Study A (n=144) investigated the prognosis of patients who were managed under the watchful waiting strategy after initial diagnosis; Study B (n=99) investigated the postoperative prognosis in patients who underwent aortic valve replacement at initial diagnosis or after watchful waiting. The primary outcomes were all-cause death in Study A and postoperative cardiovascular events in Study B. In Study A, 3 died of noncardiovascular causes during a median follow-up of 3.2 years. In Kaplan-Meier analysis, the survival curve was similar to that of an age-sex-matched general population in Japan. In Study B, 9 experienced the primary outcome during a median follow-up of 5.0 years. In Cox regression analysis, preoperative left ventricular end-systolic diameter enlargement (hazard ratio, 1.11; P=0.048) and left ventricular end-systolic diameter >45 mm (hazard ratio, 12.75; P=0.02) were significantly associated with poor postoperative prognosis. In Kaplan-Meier analysis, left ventricular end-systolic diameter >45 mm predicted a higher risk of the primary outcome (P <0.01). Watchful waiting was achieved safely in asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction. Preoperative left ventricular end-systolic diameter >45 mm predicted a poor postoperative outcome and may be an optimal cut-off value for surgical indication.

Left Ventricular Global Longitudinal Strain and H2FPEF Score in Chronic Kidney Disease Patients with Preserved Left Ventricular Ejection Fraction

Abstract Background Cardiovascular disease is the leading cause of mortality in patients with chronic kidney disease (CKD). Although they have mostly normal left ventricular systolic functions using conventional echocardiography some of them develop symptoms of heart failure with preserved ejection fraction (HFpEF) (Dubin et al, 2017), (Edwards et al, 2008). Objective This study aims to assess left ventricular global longitudinal strain and H2FPEF score in chronic kidney disease patients with preserved left ventricular ejection fraction. Patients and Methods The current study was a prospective study that included a total of 100 patients who were referred to our center (Ain Shams University Hospitals) nephrology clinic. Data was collected on patient arrival to our hospital and then echocardiography including LVGLS was done to all patients. All clinical and echocardiographic data were utilized do assess HfPEF probability using H2FPEF score. Results The mean age of our patients was 43.2±15.7 years and 58% of the patients were men. Ninety- five % of patients were hypertensives with more than 94 % receiving two or more anti-hypertensive medications while atrial fibrillation was found in 30% of the patients. Dialysis patients (stage Vd CKD) represented 52% of patients while stage III CKD represented 43% of patients. The patients’ hemoglobin ranged from 9-13.5 gm/dl with mean 10.415 ± 1.259. According to H2FPEF score, 29 (29%) patients had high probability to have HFpEF. Left ventricular Global longitudinal strain (GLS) in 54 patients was less negative than -16 (65.85%). Global longitudinal strain GLS showed positive correlation with H2FPEF score r = 0.406, P-value &amp;lt;0.001. Figure 1 Conclusion Chronic kidney disease is strongly associated with reduced global longitudinal strain and with high probability of HFPEF.

Severe Mitral Regurgitation in Paradoxical Low-Flow Low-Gradient Severe Aortic Stenosis.

Patients with paradoxical low-flow, low-gradient severe aortic stenosis (LFLGAS) exhibit low transvalvular flow rate (Q), while maintaining preserved left ventricular ejection fraction (LVEF). Concomitant severe mitral regurgitation (MR) contributes to the low flow state, adding complexity to diagnosis and management. This study aimed to examine the impact of severe MR on outcomes in paradoxical LFLGAS. Data from an institutional echo database identified 1,189 patients with adjudicated severe aortic stenosis (AVA≤1.0 cm 2 ), low transaortic gradients (mean gradient<40 mmHg), preserved LVEF (≥50%), and low flow rate (Q≤210 ml/sec), to confirm paradoxical LFLGAS. Subgroups were based on MR severity (severe and non-severe). Clinical outcomes included all-cause mortality, aortic valve replacement (AVR), heart failure hospitalizations, and a composite outcome. In the severe MR group (n=80), patients had lower flow rates, increased LV dimensions and a more eccentric hypertrophy pattern compared to non-severe MR (n=1,109). Over a median 5-year follow-up, severe MR correlated with higher all-cause mortality (p=0.02) and AVR rates (p=0.012). After adjustment, severe MR was independently associated with increased all-cause mortality risk (HR=1.43, p=0.011) and composite outcome (HR=1.64, p<0.001). AVR significantly reduced mortality at every MR degree, with the most substantial impact in severe MR (HR=0.18, p<0.001). Propensity-adjusted models demonstrated a stronger AVR impact with increasing MR degree (p-for-interaction=0.044). Severe MR in paradoxical LFLGAS is associated with adverse outcomes and distinctive LV remodeling. Aortic valve replacement improves survival across all MR grades, with greater impact in severe MR.

Routine beta-blocker therapy after acute coronary syndromes: The end of an era?

Beta-blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre-coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta-blockers after ACS in the absence of LV dysfunction has been challenged. The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles. Recently, the REDUCE-AMI trial-the first adequately powered randomized trial in the reperfusion era to test beta-blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)-showed no benefit on the composite of all-cause death or myocardial infarction over a median 3.5-year follow-up. While the benefit of beta-blockers in patients with reduced LVEF remains undisputed, their value in post-ACS patients with mildly reduced systolic function (LVEF 41%-49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta-blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1-12 months after ACS in patients with LVEF >40%. We believe that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LV systolic function.

Rule-based natural language processing to examine variation in worsening heart failure hospitalizations by age, sex, race and ethnicity, and left ventricular ejection fraction

BackgroundPrior studies characterizing worsening heart failure events (WHFE) have been limited in using structured healthcare data from hospitalizations, and with little exploration of sociodemographic variation. The current study examined the impact of incorporating unstructured data to identify WHFE, describing age-, sex-, race and ethnicity-, and left ventricular ejection fraction (LVEF)-specific rates. MethodsAdult members of Kaiser Permanente Southern California (KPSC) with a HF diagnosis between 2014-2018 were followed through 2019 to identify hospitalized WHFE. The main outcome was hospitalizations with a principal or secondary HF discharge diagnosis meeting rule-based Natural Language Processing (NLP) criteria for WHFE. In comparison, we examined hospitalizations with a principal discharge diagnosis of HF. Age-, sex-, and race and ethnicity-adjusted rates per 100 person-years (PY) were calculated among age, sex, race and ethnicity (non-Hispanic (NH) Asian/Pacific Islander [API], Hispanic, NH Black, NH White) and LVEF subgroups. ResultsAmong 44,863 adults with HF, 10,560 (23.5%) had an NLP-defined, hospitalized WHFE. Adjusted rates (per 100 PY) of WHFE using NLP were higher compared to rates based only on HF principal discharge diagnosis codes (12.7 and 9.3, respectively), and this followed similar patterns among subgroups, with the highest rates among adults ≥75 years (16.3 and 11.2), men (13.2 and 9.7), and NH Black (16.9 and 14.3) and Hispanic adults (15.3 and 11.4), and adults with reduced LVEF (16.2 and 14.0). Using NLP disproportionately increased the perceived burden of WHFE among API and adults with mid-range and preserved LVEF. ConclusionRule-based NLP improved the capture of hospitalized WHFE above principal discharge diagnosis codes alone. Applying standardized consensus definitions to EHR data may improve understanding of the burden of WHFE and promote optimal care overall and in specific sociodemographic groups.

Effects of beta-blockers on quality of life and well-being in patients with myocardial infarction and preserved left ventricular function-a prespecified substudy from REDUCE-AMI.

In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being. From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P>0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results. Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.

CMR to characterize myocardial structure and function in heart failure with preserved left ventricular ejection fraction.

Despite remarkable progress in therapeutic drugs, morbidity, and mortality for heart failure (HF) remains high in developed countries. HF with preserved ejection fraction (HFpEF) now accounts for around half of all HF cases. It is a heterogeneous disease, with multiple aetiologies, and as such poses a significant diagnostic challenge. Cardiac magnetic resonance (CMR) has become a valuable non-invasive modality to assess cardiac morphology and function, but beyond that, the multi-parametric nature of CMR allows novel approaches to characterize haemodynamics and with magnetic resonance spectroscopy (MRS), the study of metabolism. Furthermore, exercise CMR, when combined with lung water imaging provides an in-depth understanding of the underlying pathophysiological and mechanistic processes in HFpEF. Thus, CMR provides a comprehensive phenotyping tool for HFpEF, which points towards a targeted and personalized therapy with improved diagnostics and prevention.

Left ventricular diastolic dysfunction in non-myocardial disorders.

This article reviews and discusses non-myocardial disorders that represent diagnostic challenges when evaluating patients for suspected heart failure with preserved left ventricular ejection fraction. This includes pre-capillary pulmonary hypertension, which is important to differentiate from post-capillary hypertension caused by left-sided heart disease. The impact of electrical disorders on LV diastolic function is also reviewed, and includes a discussion of left bundle branch, which has both a direct effect on LV diastolic function, as well as a long-term effect due to remodelling. Furthermore, evaluation of diastolic function in patients with atrial fibrillation is discussed. Pericardial diseases are reviewed as well as effects of a normal pericardium on diastolic function in failing hearts. Finally, the article reviews how valvular diseases impact LV diastolic function.

Evaluation of left ventricular systolic function in patients with iron deficiency anemia based on non-invasive left ventricular pressure–strain loops

BackgroundIron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press–strain loop (LV-PSL).MethodsSixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL < Hb < 9 g/dL. Thirty-three healthy individuals were used as the control (Group A). The global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global waste work (GWW), global work efficiency (GWE) were derived using LV-PSL analysis. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal left ventricular systolic function in IDA patients.ResultsCompared to group A, GWI and GCW were reduced in group B (both P < 0.01). Compared with groups B and A, GLS, GWI, GCW and GWE, and E/A were all diminished, and GWW, LVEDV, LVESV, and E/mean e’ were all increased in group C (all P < 0.01). GLS was positively correlated with GWI, GCW, and GWE (r = 0.679, 0.681, and 0.447, all P < 0.01), and negatively associated with GWW (r = − 0.411, all P < 0.01). For GWI, area under the ROC curve (AUROC) was 0.783. The optimal GWI threshold for detecting abnormal LV systolic function in IDA was1763 mmHg%, with sensitivity of 0.71 and specificity of 0.78.ConclusionsLV-PSL allows noninvasive quantitative assessment of early impaired LV systolic function in IDA patients with preserved LV ejection fraction, and GWI has high sensitivity and specificity compared with other parameters.

Prognostic values of left atrial strain analyzed by four-dimensional speckle tracking echocardiography in uremia with preserved ejection fraction

Little is known about the prognostic value of left atrial strain by four-dimensional speckle-tracking echocardiography in end-stage renal disease patients with preserved left ventricular ejection fraction. This prospective study collected clinical and echocardiographic data from 80 stable dialysis patients (mean age 57 ± 10 years; 62.5% men). All patients underwent the dedicated four-dimensional speckle-tracking echocardiography to measure LASr (peak longitudinal strain of reservoir function), LAScd (peak longitudinal strain of conduit function), LASct (peak longitudinal strain of contractile function), LASr_c (peak circumferential strain of reservoir function), LAScd_c (peak circumferential strain of conduit function) and LASct_c (peak circumferential strain of contractile function). These patients were enrolled from August 2021 to August 2023 and followed-up for 19 months (interquartile-range 15 to 20 months). The primary outcome was a composite of all-cause mortality or major adverse cardiovascular events (MACEs). The study patients were classified into event (developed mortality or MACEs) and event-free group according to the primary outcome. Multivariate Cox regression analysis was used to investigate risk factors for all-cause mortality or MACEs. The event group had lower LASr (16.4% vs. 21.2%, P = 0.0003), LASct (8.2% vs. 11.2%, P = 0.01), LASr_c (25.2% vs. 35.0%, P = 0.0004) and LASct_c (14.9% vs. 20.9%, P = 0.001) than the event-free group. Using optimal cut-off value determined by ROC curve, the less LASr (LASr < 18.5%), LASct (LASct < 8.5%), LASr_c (LASr_c < 28.5%), and LASct_c (LASct_c < 17.5%) group had a higher mortality or MACEs rate. Multivariate cox regression analyses revealed that LASr (HR = 0.81, 95% CI [0.17; 0.91], P = 0.0005, per 1% increase) and LASr_c (HR = 0.93, 95% CI [0.87; 0.98], P = 0.01, per 1% increase) were independent predictors of all-cause mortality or MACEs. Less peak longitudinal and circumferential strains of reservoir function are predictive of poor prognosis among end-stage renal disease patients with preserved left ventricular ejection fraction.

Impact of sex on clinical and laboratory parameters in patients with heart failure: insights from the Colombian Heart Failure Registry (RECOLFACA)

Introduction Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. This study aimed to assess the impact of sex on sociodemographic, clinical, and laboratory parameters in patients with HF who were included in the Colombian Heart Failure Registry (RECOLFACA). Methods This was a cross-sectional analytical research. All 2528 patients included in RECOLFACA were analysed. The Mann–Whitney U test was used to compare median values as well as first and third quartiles (Q1–Q3). The age-related trend of NT-proBNP levels for both men and women groups was statistically evaluated. Results The study included 2528 patients with HF (1072 women and 1456 men). The echocardiographic evidence showed that men presented reduced left ventricular ejection fraction (LVEF) (79.63 vs. 69.75%, respectively; p < 0.001) more often than women, which had a significantly higher proportion of preserved LVEF (20.46 vs.11.24%, respectively; p < 0.001). Women displayed a higher value of systolic blood pressure (p < 0.001) and heart rate (p = 0.014) compared to men. Haemoglobin, creatinine, and sodium levels were significantly higher in men. Men had a considerably lower glomerular filtration rate value, with the median reaching a G3a value for chronic renal failure. According to age, the levels of NT-proBNP in each sex increased equivalently with age. Conclusion Sex differences presented in this study are comparable to those discovered in other nations. However, certain variations show that these sex differences may differ by geographical area, which should encourage further investigations to describe them.

Cardiovascular magnetic resonance reveals myocardial involvement in patients with active stage of inflammatory bowel disease.

Active inflammatory bowel disease (A-IBD) but not remission (R-IBD) has been associated with an increased risk of cardiovascular death and hospitalization for heart failure. Using cardiovascular magnetic resonance (CMR), this study aims to assess adverse myocardial remodeling in patients with IBD in correlation with disease activity. Forty-four IBD patients without cardiovascular disease (24 female, median-age: 39.5years, 26 A-IBD, 18 R-IBD) and 44 matched healthy volunteers (HV) were prospectively enrolled. The disease stage was determined by endoscopic and patient-reported criteria. Participants underwent CMR for cardiac phenotyping: cine imaging and strain analysis were performed to assess ventricular function. T1 mapping, extracellular volume and late-gadolinium enhanced images were obtained to assess focal and diffuse myocardial fibrosis. Simultaneous T1 and T2 elevation (T1 > 1049.3ms, T2 > 54ms) was considered to indicate a myocardial segment was inflamed. 16/44 (16.4%) IBD patients described dyspnea on exertion and 10/44 (22.7%) reported chest pain. A-IBD patients showed impaired ventricular function, indicated by reduced global circumferential and radial strain despite preserved left-ventricular ejection fraction. 16% of all IBD patients had focal fibrosis in a non-ischemic pattern. A-IDB patients had increased markers of diffuse left ventricular fibrosis (T1-values: A-IBD: 1022.0 ± 34.83ms, R-IBD: 1010.10 ± 32.88ms, HV: 990.61 ± 29.35ms, p < .01). Significantly more participants with A-IDB (8/26, 30.8%) had at least one inflamed myocardial segment than patients in remission (0/18) and HV (1/44, 2.3%, p < .01). Markers of diffuse fibrosis correlated with disease activity. This study, using CMR, provides evidence of myocardial involvement and patterns of adverse left ventricular remodeling in patients with IBD. ISRCTN30941346.

Patterns of Left Ventricular Remodelling in Children and Young Patients with Hypertrophic Cardiomyopathy.

Introduction: The aim of this study was to evaluate the age at onset, clinical course, and patterns of left ventricular (LV) remodelling during follow-up in children and young patients with hypertrophic cardiomyopathy (HCM). Methods: We included consecutive patients with sarcomeric or non-syndromic HCM below 18 years old. Three pre-specified patterns of LV remodelling were assessed: maximal LV wall thickness (MLVWT) thickening; MLVWT thinning with preserved LV ejection fraction; and MLVWT thinning with progressive reduction in LV ejection fraction (hypokinetic end-stage evolution). Results: Fifty-three patients with sarcomeric/non-syndromic HCM (mean age 9.4 ± 5.5 years, 68% male) fulfilled the inclusion criteria. In total, 32 patients (60%) showed LV remodelling: 3 patients (6%) exhibited MLVWT thinning; 16 patients (30%) showed MLVWT thickening; and 13 patients (24%) progressed to hypokinetic end-stage HCM. Twenty-one patients (40%) had no LV remodelling during follow-up. In multivariate analysis, MLVWT was a predictor of the hypokinetic end-stage remodelling pattern during follow-up (OR 1.17 [95%CI 1.01-1.36] per 1 mm increase, p-value 0.043), regardless of sarcomeric variants and New York Heart Association class. Two patients with sarcomeric HCM, showing a pattern of MLVWT regression during childhood, experienced progression during adolescence. Conclusions: Different patterns of LV remodelling were observed in a cohort of children with sarcomeric/non-syndromic HCM. Interestingly, a pattern of progressive MLVWT thinning during childhood, with new progression of MLVWT during adolescence, was noted. A better understanding of the remodelling mechanisms in children with sarcomeric HCM may be relevant to defining the timing and possible efficacy of new targeted therapies in the preclinical stage of the disease.

Impaired Cardiac Sympathetic Activity Is Associated With Myocardial Remodeling and Established Biomarkers of Heart Failure.

123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels. Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.

New-onset atrial high-rate episodes in left bundle branch area pacing versus right ventricular pacing for patients with atrioventricular block.

Left bundle branch area pacing (LBBAP) demonstrated beneficial effects on clinical outcomes. Comparative data on the risk of atrial high-rate episodes (AHREs) between LBBAP and right ventricular pacing (RVP) are lacking. This study aimed to investigate whether LBBAP can reduce the risk of new-onset AHREs compared with RVP in patients with atrioventricular block (AVB). We enrolled 175 consecutive AVB patients with no history of atrial fibrillation undergoing dual-chamber pacemaker implantation (LBBAP or RVP). Propensity score matching for baseline characteristics yielded 43 matched pairs. The primary outcome was new-onset AHREs detected on a scheduled device follow-up. Changes in echocardiographic measurements were also compared between the groups. New-onset AHREs occurred in 42 (24.0%) of all enrolled patients (follow-up 14.1 [7.5] months) and the incidence of new-onset AHREs in the LBBAP group was lower than in the RVP group (19.8% vs. 34.7%; P = 0.04). After propensity score matching, LBBAP still resulted in a lower incidence of new-onset AHREs (11.6% vs. 32.6%; P = 0.02), and a lower hazard ratio for new-onset AHREs compared with RVP (HR, 0.274; 95% CI, 0.113-0.692). At 1 year, LBBAP achieved preserved left ventricular ejection fraction (LVEF) (63.0 [3.2]% to 63.1 [3.1]%; P = 0.56), while RVP resulted in reduced LVEF (63.4 [4.9]% to 60.5 [7.3]%; P = 0.01]). Changes in LVEF were significantly different between the 2 groups (by 2.6% [0.2 to 5.0]%; P = 0.03). LBBAP demonstrated a reduced risk of new-onset AHREs compared with RVP in patients with AVB.

Left Atrial Strain for assessment of left ventricle diastolic dysfunction in acute coronary syndrome patients.

Patients with acute coronary syndrome (ACS) have a high incidence of Left ventricle diastolic dysfunction (DD). Latest algorithms for the assessment of DD lay on 2D parameters and describe a grading to quantify its severity. However, there persists a "gray zone" of values in which DD remains indeterminate. to analyze the diagnostic value of Left atrium strain (LAS) for categorization of LV DD and assessment of LV filling pressures in ACS patients. Cross-sectional study that prospectively evaluated 105 patients presenting ACS with preserved LV ejection fraction (LVEF). Patients were divided in 4 groups according to the DD grade. Mean values of LAS, corresponding to three phases of atrial function: reservoir (LASr), conduit (LAScd) and contraction (LASct), were obtained by speckle-tracking echocardiography. Mean age was 60±10 years, with a gender ratio of 6.14. LASr and LASct were significantly lower according to DD severity (p combined=0.021, p combined=0.034; respectively). E/e' ratio was negatively correlated to LASr (r= - 0.251; p= 0.022) and LASct (r= -0.197; p=0.077). Left atrial volume index (LAVI) was also negatively correlated to LASr (r= -0.294, p= 0.006) and LASct (r= -0.3049, p=0.005). Peak tricuspid regurgitation was negatively correlated to LASr (r=-0.323, p=0.017) and LASct (r=-0.319, p=0.020). Patients presenting elevated LV filling pressures had lower LASr and LASct (p=0.049, p=0.022, respectively) compared to patients witn normal LV filling pressures. ROC curve analysis showed that a LASr < 22% (Se= 75%, Sp= 73%) and a LASct < 13% (Se= 71%, Sp=58%) can increase the likelihood of DD grade II or III by 4.6 (OR= 4.6; 95% CI: 1.31-16.2; p=0.016) and 3.7 (OR= 3.7; 95% CI: 1.06-13.1; p= 0.047), respectively. LAS is a valuable tool, which can be used to categorize DD in ACS patients.

Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.

The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.

Beyond the matrix: exploring tenascin-c (TNC) as a crucial player in diabetic cardiovascular dysfunction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Burgermeister Found Wien-Project number : 21001 Introduction Diabetic cardiomyopathy (CMP) is a complex manifestation of diabetes-linked cardiac and vascular dysfunction, but the molecular pathogenesis is still largely unknown. Notably the expression of Tenascin-C (TNC), an extracellular matrix glycoprotein, contributes to the development of cardiovascular diseases and diabetic patients have elevated serum TNC levels. However, the role and mechanism of TNC to diabetic CMP progression remains elusive. Purpose Here, we longitudinally evaluated functional and molecular role of TNC in CMP-induced cardiovascular dysfunction in a murine model. In addition, we used RNA sequencing with cardiac tissues from non-diabetic and diabetic wild type (wt) and TNC KO mice for further investigation. Methods Diabetes was induced in adult male mice, wt (AJ) and TNC-KO strains, by repeated Streptozotocin (STZ) injections (50 mg/kg). Echocardiography, myography, hemodynamics, histology, molecular and cellular analyses were performed to assess the role of TNC in diabetes-associated CV complications. Additionally, RNA-sequencing was analyzed in left ventricular (LV) tissue samples from diabetic and non-diabetic wt and TNC-KO mice providing further molecular insights. Results TNC KO mice showed preserved LV ejection fraction, and endothelium-dependent relaxation (p&amp;lt;0.05 and p&amp;lt;0.001, respectively), reduced cardiac fibrosis and distinctive coronary vessel characteristics, implying enhanced LV perfusion. In addition, the plasma levels of oxidative stress marker malondialdehyde was significantly alleviated in TNC KO diabetic mice in comparison to diabetic wt mice. Cardiomyocytes from diabetic wt mice exhibited stiffness (Fpassive and Factive), which was corrected to control level in cardiomyocytes from TNC KO diabetic hearts. Further, ex vivo isolated heart experiments demonstrated that the administration of recombinant human TNC (80 ng/ml) resulted in a significant reduction in LV hemodynamics (p&amp;lt;0.01) and myocardial energetics (ATP levels, p&amp;lt;0.01). Analysis of RNA sequencing data demonstrated that decreased expression of matrix remodeling genes Serpin1 and Ccn1 links to alleviation of fibrosis in TNC KO diabetic heart. Furthermore, Gene Ontology (GO) enrichment analysis shed light on mitochondrial changes in diabetic hearts. Our pathway analysis also identified that Hsp90aa1 as a crucial gene associated with preprotein import into the mitochondrial membrane, may suggest potential mitochondrial dysfunction in diabetic hearts. Conclusion In conclusion, lack of TNC improved long-term cardiac function in diabetes by reducing cardiac fibrosis, vascular dysfunction, oxidative stress and cardiac energetics. Thus, inhibition of TNC may prevent the diabetic heart from extensive fibrosis and energetics dysfunction that accelerates the development of HF, providing a potential targeted therapy.

Long-term outcome after catheter ablation for fascicular ventricular tachycardia in a single high-volume center in Germany

Abstract Background Idiopathic Fascicular Ventricular Tachycardia (IFVT) accounts for less than 10% of all VTs and represents the most common idiopathic ventricular tachycardia of the left ventricle. This study reports on clinical and procedural characteristics and the long-term outcome of patients undergoing catheter ablation of premature ventricular complexes (PVC) and ventricular tachycardias (VTs) arising in proximity of the left ventricular conduction system. Methods and results This study includes 27 patients (17 male, 45 ± 17 years; 10 females, 50 ± 11 years) who underwent electrophysiological examinations at a tertiary ablation center over a period of 14 years (2009 to 2022). Follow-up was performed via regular Holter-ECGs and clinical evaluations, or via structured follow-up within the prospective TRUST registry. In 21/27 patients (77.8%), the left posterior fascicle (LPF) was involved in the IFVT. In 4 (14.8%) the left anterior fascicle (LAF) was involved and in 2 (7.4%) patients an origin in the upper septal (US) area was demonstrated. 22/27 (81.5%) patients had a preserved left ventricular ejection fraction (LVEF) and only 5 (18.5%) patients had a LVEF less than 50% at the time of presentation. 14/27 (51.9%) patients presented with PVC or non-sustained VTs with the following distribution: 10 (71.4%) originating from the LPF, 3 (21.4%) from the LAF and 1 (7.1%) from the US. 21/27 (77.8%) patients presented with sustained VTs: 16 (76.2%) arising from the LPF, 4 (19%) from the LAF and 1 (4.8%) from the US. However, only 2 (7.4%) patients presented in sustained VT at the beginning of the EP procedure. In 16 (59.3%) patients a sustained VT was induced during the EP study via isoprenaline and/or programmed ventricular stimulation. Mean QRS duration of the VT was 124.5 ± 14.6 msec. In 21 (77.7%) patients only a retrograde approach was used, in 3 (11.1%) patients a retrograde and an additional transeptal approach and in only 3 (11.1%) patients solely a transeptal approach. Mean number of radiofrequency applications was 11.8 ± 12.6 (30 to 40 Watts, 27545.6 ± 30524.4 Joules). FVT ablation was acutely successful in 24 patients (88.9%). In 2 patients (7.4%) no ablation was performed due to inability to induce VT under sedation. 3/27 patients (11.1%) underwent re-ablation due to FVT recurrence after previous ablation procedures. Moreover, 3 (11.1%) additional patients underwent repeated VT ablations during follow-up, but the arrhythmia originated from a different LV area. No procedure-related complication occurred. In 4 patients (14.8%) left fascicular posterior block was caused by ablation and in 3 (11.1%) patients a complete left bundle block. Mean procedure time was 130 ± 48.9 minutes. Conclusion Ablation of FVT in a tertiary ablation center is associated with a high single procedural success rate of 88.9% during long-term follow-up, with a mild risk of fascicular injury. 11.1% of patients underwent re-ablation due to FVT recurrence.

Delivering effective, comprehensive, multi-exercise component cardiac rehabilitation (CR) for chronic heart failure patients in low resource settings in sub-Saharan Africa: Queen Elizabeth Central Hospital-(QECH-CR) randomised CR study, Malawi.

The delivery of Cardiac Rehabilitation (CR) and attaining evidence-based treatment goals are challenging in developing countries, such as Malawi. The aims of this study were to (i) assess the effects of exercise training/ CR programme on cardiorespiratory and functional capacity of patients with chronic heart failure (CHF), and (ii) examine the effectiveness of a novel, hybrid CR delivery using integrated supervised hospital- and home-based caregiver approaches. A pre-registered (UMIN000045380), randomised controlled trial of CR exercise therapy in patients with CHF was conducted between September 2021 and May 2022. Sixty CHF participants were randomly assigned into a parallel design-exercise therapy (ET) (n = 30) or standard of care (n = 30) groups. Resting hemodynamics, oxygen saturation, distance walked in six-minutes (6MWD) and estimated peak oxygen consumption (VO2 peak) constituted the outcome measures. The exercise group received supervised, group, circuit-based ET once weekly within the hospital setting and prescribed home-based exercise twice weekly for 12 weeks. Participants in both arms received a group-based, health behaviour change targeted education (usual care) at baseline, 8-, 12- and 16-weeks. Most of the participants were female (57%) with a mean age of 51.9 ±15.7 years. Sixty-five percent (65%) were in New York Heart Association class III, mostly with preserved left ventricular ejection fraction (HFpEF) (mean Left Ventricular Ejection Fraction 52.9 ±10.6%). The 12-weeks ET led to significant reductions in resting haemodynamic measures (all P <0.05). The ET showed significantly higher improvements in the 6MWD (103.6 versus 13.9 m, p<0.001) and VO2 peak (3.0 versus 0.4 ml·kg-1·min-1, p <0.001). Significant improvements in 6MWD and VO2 peak (both p<0.001), in favour of ET, were also observed across all follow-up timepoints. This novel, randomised, hybrid ET-based CR, delivered to mainly HFpEF patients using an integrated hospital- and home-based approach effectively improved exercise tolerance, cardiorespiratory fitness capacities and reduced perceived exertion in a resource-limited setting.