[New Treatment Strategies in Patients with Heart Failure with Reduced Ejection Fraction: Beyond Neurohormonal Inhibition].

Patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) are prone to experience episodes of worsening symptoms and signs despite continued therapy, termed "worsening heart failure" (WHF). Although guideline-directed medical therapy is well established, worsening of chronic heart failure accounts for almost 50% of all hospital admissions for HF with consequent higher risk of death and hospitalization than patients with "stable" HF. New drugs are emerging as cornerstones to reduce residual risk of both cardiovascular mortality and readmission for heart failure. The following review will debate about emerging definition of WHF in light of the recent clinical consensus released by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the new therapeutic strategies in cardiorenal patients.

Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania.

BACKGROUND: The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. METHODS: In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). RESULTS: Median age of the 110 participants was 28.5 years (range 17-45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15-46). After a median follow-up of 8.98 months (IQR 5.72-29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6-77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10-2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19-0.82, p = 0.012). CONCLUSION: Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Cost-utility analysis of add-on vericiguat for the treatment of chronic heart failure with reduced ejection fraction in China.

OBJECTIVE: This study aimed to evaluate the cost-utility of the addition of vericiguat for treating chronic heart failure (CHF) in China from the healthcare payer's perspective. METHODS: A Markov model was built to estimate the cost and utility of treating CHF using vericiguat plus standard treatment (vericiguat group) vs. standard treatment alone (standard treatment group). The clinical parameters (mortality of cardiovascular and hospitalization rate of HF) were calculated according to the VICTORIA clinical trial. The HF cost and utility data were obtained from the literature published in China. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: According to the 13-year model, vericiguat was more expensive (155599.07 CNY vs. 259396.83 CNY) and more effective (4.41 QALYs vs. 4.54 QALYs). The incremental cost-utility ratio (ICUR) was 802389.27 CNY per QALY. One-way sensitivity analysis revealed that cardiovascular mortality in the two groups was the parameter that had the greatest impact on the results. The GDP per capita in 2022 in China was 85,700 CNY. The probability sensitivity analysis (PSA) showed that the probability of vericiguat being cost-effective was only 41.7% at the willingness-to-pay (WTP) threshold of 3 times GDP per capita (257,100 CNY). CONCLUSIONS: In China, the treatment of CHF with vericiguat is not cost-effective. The drug price could decrease to 145.8 CNY, which could be considered cost-effective.

Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction.

BACKGROUND: Despite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking. METHODS: A survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4-5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest. RESULTS: Cardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07-3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18-4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01-3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48-4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine. CONCLUSIONS: Our results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis.

BACKGROUND: Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost. OBJECTIVE: We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies. METHODS: Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label. RESULTS: Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: -0.44 (95% CI -0.49 to -0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy. CONCLUSIONS: Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.

Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study.

We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Cardiac function in a large animal model of myocardial infarction at 7 T: deep learning based automatic segmentation increases reproducibility.

Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson's r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium.

Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study.

PURPOSE: The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF. METHODS: This cohort study using MarketScan® Commercial and Medicare supplemental databases (2012-2020) included patients aged ≥ 18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort. RESULTS: The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95% confidence interval [CI] 0.36-1.14) or between empagliflozin and canagliflozin (aHR 1.25; 95% CI 0.77-2.05). Similarly, there was no evidence of difference between dapagliflozin and empagliflozin in this risk (aHR 0.76; 95% CI 0.48-1.21). The results of analyses separately assessing UTI or genital infection were similar. CONCLUSIONS: There was no significant difference in the risk of UTI or genital infection among patients with HFpEF who initiated canagliflozin, dapagliflozin, or empagliflozin.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used for the management of heart failure with preserved ejection fraction (HFpEF). It is important to assess their comparative risk of urinary tract infection (UTI) or genital infection among patients with HFpEF. We compared patients with HFpEF using SGLT2i in three pairwise groups: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. We found that there was no significant difference in the risk of genitourinary infections including UTI or genital infections among dapagliflozin, empagliflozin, and canagliflozin.

Definition and management of arrhythmia-induced cardiomyopathy: findings from the European Heart Rhythm Association survey.

AIMS: Arrhythmia-induced cardiomyopathy (AiCM) represents a subtype of acute heart failure (HF) in the context of sustained arrhythmia. Clear definitions and management recommendations for AiCM are lacking. The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to explore the current definitions and management of patients with AiCM among European and non-European electrophysiologists. METHODS AND RESULTS: A 25-item online questionnaire was developed and distributed among EP specialists on the EHRA SIC website and on social media between 4 September and 5 October 2023. Of the 206 respondents, 16% were female and 61% were between 30 and 49 years old. Most of the respondents were EP specialists (81%) working at university hospitals (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia, only 35% identified a specific LVEF drop to diagnose AiCM with a wide range of values (5-20% LVEF drop). Most respondents considered all available therapies: catheter ablation (93%), electrical cardioversion (83%), antiarrhythmic drugs (76%), and adjuvant HF treatment (76%). A total of 83% of respondents indicated that adjuvant HF treatment should be started at first HF diagnosis prior to antiarrhythmic treatment, and 84% agreed it should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first LVEF reassessment during follow-up varied markedly (1 day-6 months after antiarrhythmic treatment). CONCLUSION: This EHRA Survey reveals varying practices regarding AiCM among physicians, highlighting a lack of consensus and heterogenous care of these patients.

Prediction of heart failure patients with distinct left ventricular ejection fraction levels using circadian ECG features and machine learning.

Heart failure (HF) encompasses a diverse clinical spectrum, including instances of transient HF or HF with recovered ejection fraction, alongside persistent cases. This dynamic condition exhibits a growing prevalence and entails substantial healthcare expenditures, with anticipated escalation in the future. It is essential to classify HF patients into three groups based on their ejection fraction: reduced (HFrEF), mid-range (HFmEF), and preserved (HFpEF), such as for diagnosis, risk assessment, treatment choice, and the ongoing monitoring of heart failure. Nevertheless, obtaining a definitive prediction poses challenges, requiring the reliance on echocardiography. On the contrary, an electrocardiogram (ECG) provides a straightforward, quick, continuous assessment of the patient's cardiac rhythm, serving as a cost-effective adjunct to echocardiography. In this research, we evaluate several machine learning (ML)-based classification models, such as K-nearest neighbors (KNN), neural networks (NN), support vector machines (SVM), and decision trees (TREE), to classify left ventricular ejection fraction (LVEF) for three categories of HF patients at hourly intervals, using 24-hour ECG recordings. Information from heterogeneous group of 303 heart failure patients, encompassing HFpEF, HFmEF, or HFrEF classes, was acquired from a multicenter dataset involving both American and Greek populations. Features extracted from ECG data were employed to train the aforementioned ML classification models, with the training occurring in one-hour intervals. To optimize the classification of LVEF levels in coronary artery disease (CAD) patients, a nested cross-validation approach was employed for hyperparameter tuning. HF patients were best classified using TREE and KNN models, with an overall accuracy of 91.2% and 90.9%, and average area under the curve of the receiver operating characteristics (AUROC) of 0.98, and 0.99, respectively. Furthermore, according to the experimental findings, the time periods of midnight-1 am, 8-9 am, and 10-11 pm were the ones that contributed to the highest classification accuracy. The results pave the way for creating an automated screening system tailored for patients with CAD, utilizing optimal measurement timings aligned with their circadian cycles.

Evaluation of renal sodium handling in heart failure with preserved ejection fraction: A pilot study.

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.

Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Clinical study: the impact of goal-directed fluid therapy on volume management during enhanced recovery after surgery in gastrointestinal procedures.

Background: Goal-directed fluid therapy, as a crucial component of accelerated rehabilitation after surgery, plays a significant role in expediting postoperative recovery and enhancing the prognosis of major surgical procedures. Methods: In line with this, the present study aimed to investigate the impact of target-oriented fluid therapy on volume management during ERAS protocols specifically for gastrointestinal surgery. Patients undergoing gastrointestinal surgery at our hospital between October 2019 and May 2021 were selected as the sample population for this research. Results: 41 cases of gastrointestinal surgery patients were collected from our hospital over 3 recent years. Compared with T1, MAP levels were significantly increased from T2 to T5; cardiac output (CO) was significantly decreased from T2 to T3, and significantly increased from T4 to T5; and SV level was significantly increased from T3 to T5. Compared with T2, HR and cardiac index (CI) were significantly elevated at T1 and at T3-T5. Compared with T3, SVV was significantly decreased at T1, T2, T4, and T5; CO and stroke volume (SV) levels were increased significantly at T4 and T5. In this study, pressor drugs were taken for 23 days, PACU residence time was 40.22 ± 12.79 min, time to get out of bed was 12.41 ± 3.97 h, exhaust and defecation time was 18.11 ± 7.52 h, and length of postoperative hospital stay was 4.47 ± 1.98 days. The average HAMA score was 9.11 ± 2.37, CRP levels were 10.54 ± 3.38 mg/L, adrenaline levels were 132.87 ± 8.97 ng/L, and cortisol levels were 119.72 ± 4.08 ng/L. Prealbumin levels were 141.98 ± 10.99 mg/L at 3 d after surgery, and 164.17 ± 15.84 mg/L on the day of discharge. Lymphocyte count was 1.22 ± 0.18 (109/L) at 3 d after surgery, and 1.47 ± 0.17 (109/L) on the day of discharge. Serum albumin levels were 30.51 ± 2.28 (g/L) at 3 d after surgery, and 33.52 ± 2.07 (g/L) on the day of discharge. Conclusion: Goal-directed fluid therapy (GDFT) under the concept of Enhanced Recovery After Surgery (ERAS) is helpful in volume management during radical resection of colorectal tumors, with good postoperative recovery. Attention should be paid to the influence of pneumoperitoneum and intraoperative posture on GDFT parameters.

Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy.

Diabetic individuals with diabetic cardiomyopathy (DbCM) present with abnormal myocardial structure and function. DbCM cannot be accurately diagnosed due to the lack of suitable diagnostic biomarkers. In this study, 171 eligible participants were divided into a healthy control (HC), type 2 diabetes mellitus (T2DM) patients without DbCM (T2DM), or DbCM group. Serum fibrinogen-like protein 1 (FGL-1) and other biochemical parameters were determined for all participants. Serum FGL-1 levels were significantly higher in patients with DbCM compared with those in the T2DM group and HCs. Serum FGL-1 levels were negatively correlated with left ventricular fractional shortening and left ventricular ejection fraction (LVEF) and positively correlated with left ventricular mass index in patients with DbCM after adjusting for age, sex and body mass index. Interaction of serum FGL-1 and triglyceride levels on LVEF was noted in patients with DbCM. A composite marker including serum FGL-1 and triglycerides could differentiate patients with DbCM from those with T2DM and HCs with an area under the curve of 0.773 and 0.789, respectively. Composite marker levels were negatively correlated with N-terminal B-type natriuretic peptide levels in patients with DbCM. Circulating FGL-1 may therefore be a valuable index reflecting cardiac functions in DbCM and to diagnose DbCM.

Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Moderate Aortic Valve Stenosis Is Associated With Increased Mortality Rate and Lifetime Loss: Systematic Review and Meta-Analysis of Reconstructed Time-to-Event Data of 409 680 Patients.

BACKGROUND: The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all-cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). METHODS AND RESULTS: A systematic review and pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15-year overall survival rate was 23.3% (95% CI, 19.1%-28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%-59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46-2.64]; P<0.001). In patients with heart failure with reduced ejection fraction, the 10-year overall survival rate was 15.5% (95% CI, 10.0%-24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%-38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69-2.0]; P<0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow-up (4.4 years, P<0.001; and 1.9 years, P<0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed. CONCLUSIONS: Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.

Infliximab Limits Injury in Myocardial Infarction.

BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Obesity and heart failure with preserved ejection fraction.

OBJECTIVE: Aim: To perform an overall assessment of heart failure with preserved ejection fraction (HFpEF) adults with central obesity. PATIENTS AND METHODS: Materials and Methods: We enrolled HFpEF patients with central obesity (n =73, mean age 52.4 ± 6.3 years) and without obesity (n =70, mean age 51.9 ± 7.1 years) and compared with an age-matched healthy subjects who had not suffered from HF (n = 69, mean age 52.3 ± 7.5 years). Physical examination, routine laboratory tests such as fasting blood glucose, fasting insulin, insulin resistance (HOMA) index, serum lipids, haemoglobin, creatinine, ALT, AST, uric acide, hs CRP, TSH, N-terminal proB-type natriuretic peptide (NT-proBNP) and standard transthoracic echocardiogram (2D and Doppler) examinations were performed and assessed. RESULTS: Results: The average values of diastolic blood pressure (DBP), glucose and lipid profiles, uric acide, hs CRP were found to be significantly higher among obese patients with HFpEF than non-obese. Despite more severe symptoms and signs of HF, obese patients with HFpEF had lower NT-proBNP values than non-obese patients with HFpEF (129±36.8 pg/ml, 134±32.5 pg/ml vs 131±30.4 pg/ml, 139±33.8 pg/ml respectively; p < 0.05). However, it was found that patients with high central (visceral) adiposity have more pronounced obesity-related LV diastolic dysfunction, lower E/e' ratio, lower mitral annular lateral e' velocity, an increased LV diastolic dimension and LV mass index. Compared with non-obese HFpEF and control subjects, obese patients displayed greater right ventricular dilatation (base, 35±3.13 mm, 36±4.7 mm vs 33±2.8 mm, 34±3.2 mm and 29±5.3 mm, 30±3.9 mm; length, 74±5 mm, 76±8 mm vs 67±4 mm, 69±6 mm and 60±3 mm, 61±5 mm respectively; p < 0.05), more right ventricular dysfunction (TAPSE 16±2 mm, 15±3 mm vs 17±2 mm, 17±1 mm and 19±2 mm, 20±3 mm respectively; p < 0.05). CONCLUSION: Conclusions: Obese patients with HFpEF have higher diastolic BP, atherogenic dyslipidemia, insulin resistance index values and greater systemic inflammatory biomarkers, despite lower NT-proBNP values, which increase the risk of cardiovascular events in future. Echocardiography examination revealed not only significant LV diastolic dysfunction, but also displayed greater RV dilatation and dysfunction.

Automatic left ventricle volume and mass quantification from 2D cine-MRI: Investigating papillary muscle influence.

OBJECTIVE: Early detection of cardiovascular diseases is based on accurate quantification of the left ventricle (LV) function parameters. In this paper, we propose a fully automatic framework for LV volume and mass quantification from 2D-cine MR images already segmented using U-Net. METHODS: The general framework consists of three main steps: Data preparation including automatic LV localization using a convolution neural network (CNN) and application of morphological operations to exclude papillary muscles from the LV cavity. The second step consists in automatically extracting the LV contours using U-Net architecture. Finally, by integrating temporal information which is manifested by a spatial motion of myocytes as a third dimension, we calculated LV volume, LV ejection fraction (LVEF) and left ventricle mass (LVM). Based on these parameters, we detected and quantified cardiac contraction abnormalities using Python software. RESULTS: CNN was trained with 35 patients and tested on 15 patients from the ACDC database with an accuracy of 99,15 %. U-Net architecture was trained using ACDC database and evaluated using local dataset with a Dice similarity coefficient (DSC) of 99,78 % and a Hausdorff Distance (HD) of 4.468 mm (p < 0,001). Quantification results showed a strong correlation with physiological measures with a Pearson correlation coefficient (PCC) of 0,991 for LV volume, 0.962 for LVEF, 0.98 for stroke volume (SV) and 0.923 for LVM after pillars' elimination. Clinically, our method allows regional and accurate identification of pathological myocardial segments and can serve as a diagnostic aid tool of cardiac contraction abnormalities. CONCLUSION: Experimental results prove the usefulness of the proposed method for LV volume and function quantification and verify its potential clinical applicability.