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BACKGROUND: Congestive heart failure (CHF) is associated with a blunted force-frequency relation (FFR) and myocardial contractile reserve (MCR) partially from a downregulation of beta1-adrenoreceptors (beta1-AR). We investigated whether acute and chronic cardiac resynchronization therapy (CRT) was capable of reversing the blunted FFR and MCR and if this was associated with upregulation of beta1-AR. METHODS AND RESULTS: Left ventricle dP/dtmax was invasively measured in 10 CHF patients (New York Heart Association class > or =3; ejection fraction <25%) during incremental dual chamber (DDD)-CRT pacing at 70, 90, 110, and 130 beats/min, with and without continuous infusion of intravenous dobutamine, immediately after CRT implantation (BL) and 4 months later (FU). In a subgroup of 5 patients, serial left ventricle beta1 and beta2-AR gene expression was measured using reverse transcriptase-polymerase chain reaction. Four months after the initiation of resynchronization therapy, DDD-CRT pacing results in a significant upward shift of the heart rate versus LV dP/dtmax relationship (P < .01) with force frequency amplification as evidenced by the steeper slope of the force frequency response (P = .04). Infusion of dobutamine recruits myocardial contractile reserve and increases the heart rate versus LV dP/dtmax relationship at BL and at FU (both P < .05). However, only at follow-up was an additional force frequency amplification noticed (P < .05) during dobutamine infusion. This observation was paralleled by a significant upregulation of beta1-AR gene expression (P = .02). CONCLUSIONS: Chronic CRT is associated with a partial restoration of the FFR and with a recruitment in myocardial contractile reserve, which is paralleled by upregulation of beta1-AR. [ABSTRACT FROM AUTHOR]

Background: Heart failure is associated with a reduction in left ventricular (LV) contractility as evidenced by a blunted force-frequency response (FFR) and downregulation of contractility regulating genes.Objective: This study sought to investigate whether cardiac resynchronization therapy (CRT) is capable of reversing the blunted FFR and the downregulation of contractility regulating genes.Methods: Twenty heart failure patients underwent echocardiographic examination during incremental AAI and DDD-CRT pacing at 70, 90, and 110 beats/min, immediately after and 4 months after CRT implantation. The FFR was determined from the ratio of the LV systolic pressure/end systolic volume index at given heart rate. In a subgroup of 6 patients with idiopathic dilated cardiomyopathy, serial LV dP/dtmax was invasively measured during both pacing modes and serial LV endomyocardial biopsies were taken to measure sarcoplasmatic reticulum calcium ATPase 2alpha (SERCA2alpha), phospholamban (PLN), sarcolemmal sodium calcium exchanger (NCX), beta1-adrenoreceptor (beta1-AR), and apelin (APL) gene expression using reverse-transcriptase polymerase chain reaction.Results: Acutely, DDD-CRT pacing was associated with a decrease in dyssynchrony (P <.01) and increase in diastolic filling time (P <.01) at all heart rates paralleled by an upward shift of the FFR (P <.01) without force-frequency amplification. A greater upward shift of the FFR was noticed during DDD-CRT as compared with AAI (P <.01) after 4 months. In addition, CRT was associated with a significant force-frequency amplification at follow-up as evidenced from the steeper slope of the FFR relationship (P = .039). This was associated with a significant upregulation of SERCA2alpha P = .01), PLN (P = .01), their ratio (P = .01), ratio of SERCA/NCX (P = .02), beta1-AR (P = .03), and APL (P = .01) mRNA levels.Conclusion: CRT is associated with an acute upward shift in the FFR without force-frequency amplification related to restored synchronicity and increased filling time of the LV. Only chronic CRT is associated with force-frequency amplification in parallel to upregulation of contractility regulating genes. [ABSTRACT FROM AUTHOR]

An abstract of the study "Cardioselective Beta-1 Blockade Impairs Maximal Exercise Capacity and Chronotropic Response to Exercise in Post-MI Patients," by C. Van laethem and colleagues is presented.

Although less invasive diagnostic procedures such as cardiac magnetic resonance, positron emission tomography, and recently strain echocardiography have become crucial in the diagnostic work-up of cardiovascular heart disease, only EMB offers a histopathologic diagnosis with unique prognostic and therapeutic implications. In this regard, EMB provides information about cellular or humoral rejection in the surveillance of heart transplant recipients and adjustment of their immunosuppressive therapy. This study aims to assess the incidence of EMB-related complications, This observational study retrospectively assessed 937 biopsies obtained in consecutive patients between May 2011 and May 2021 for surveillance of rejection episodes after HTx. Patients were stratified according to gender, age, access site and BMI resulting in 4 deferent cohorts. Procedural safety of EMB was the primary endpoint of this study, with definitions of major and minor complications based on earlier studies. The analysis revealed an overall complication rate of 2.8%. Serious life-threatening cardiac complications occurred 0.3% of EMB. More specifically tricuspid valve injury causing severe tricuspid regurgitation, pneumothorax and temporary AV block occured in 0.1%. Minor complications occurred in 2.5 % of the overall population. Pericardial effusion not requiring pericardiocentesis was the most frequently observed complication (1.8%), followed by complications related to the vascular access (0.5%). All other complications occurred in <0.1%. Complications were more often observed in female patients. No significant differences were found for the remaining major and minor complications in the different cohorts. In experienced hands, EMB for heart transplantation rejection is a safe procedure with low risk of complications. [ABSTRACT FROM AUTHOR]

Objectives: We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. Background: Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony. Methods: Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction > or =25% at 4 months after CRT were considered as responders. Results: The HF patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders. Conclusions: In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve replacement(TAVR) has shown clear survival benefits in severe aortic valve stenosis(AS). However, patients unable to recover left ventricle function remain at risk with poor long-term survival. This single-center prospective study aims to analyze the supplementary benefits of myocardial work(MW) assessment for baseline risk stratification in patients with severe AS referred for TAVR., Methods: A total of 110 patients with severe AS referred for TAVR were included in the study. Baseline ECG data, transthoracic echocardiographic(TTE) images and blood samples were obtained. The TTE examination was repeated one day and one month after valve replacement. The primary outcome of the study was a composite endpoint consisting of all-cause mortality and HF hospitalization., Results: During a mean follow-up period of 521 ± 343 days, 29patients(26.4 %) reached the composite endpoint. Baseline troponins, NT-proBNP, sST2, GWI and GCW showed statistically significant differences between groups. Patients with a baseline GWI<2323 mmHg% (sensitivity 0.63 and specificity 0.76)had significantly worse outcome following TAVR. A basic predictive model included QRS-length, TAPSE, LAVI and E/e'. The addition of biomarkers did not yield any further advantages whereas incorporating the GWI cut-off value of 2323 mmHg% significantly enhanced the predictive value. Although there were no significant changes in LVEF and GLS, all patients exhibited a significant reduction in GWI and GCW immediately after TAVR., Conclusion: Our findings provide evidence for the enhanced usefulness of MW analysis in the initial risk stratification of patients with severe AS referred for TAVR. Specifically, a baseline GWI<2323 mmHg% demonstrates an independent predictor associated with increased incidence of all-cause mortality and HF hospitalization following TAVR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Acute decompensated heart failure (ADHF) is a major cause of hospitalizations in older adults, leading to high mortality, morbidity, and healthcare costs. To address the persistent poor outcomes in ADHF, novel device-based approaches targeting specific pathophysiological mechanisms are urgently needed. The recently introduced DRI 2 P 2 S classification categorizes these innovative therapies based on their mechanisms. Devices include dilators (increasing venous capacitance), removers (directly removing sodium and water), inotropes (enhancing left ventricular contractility), interstitials (accelerating lymph removal), pushers (increasing renal arterial pressure), pullers (decreasing renal venous pressure), and selective drippers (selective intrarenal drug infusion). Some are tailored for chronic HF, while others focus on the acute setting. Most devices are in early development, necessitating further research to understand mechanisms, assess clinical effectiveness, and ensure safety before routine use in ADHF management. Exploring these innovative device-based strategies may lead to improved outcomes and revolutionize HF treatment in the future., Competing Interests: Declaration of Competing Interest DTB, PP, MB, GE, DF, CV, AL and MMV are supported by a research grant from the CardioPaTh PhD Program. The remaining authors have nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive and fatal cardiomyopathy, is frequently misdiagnosed or entails diagnostic delays, hindering patients from timely treatment. This study aimed to generate a systematic framework based on data from electronic health records (EHRs) to assess patients with ATTR-CM in a real-world population of heart failure (HF) patients. Predictive factors or combinations of predictive factors related to ATTR-CM in a European population were also assessed., Methods and Results: Retrospective unstructured and semi-structured data from EHRs of patients from OLV Hospital Aalst, Belgium (2012-20), were processed using natural language processing (NLP) to generate an Observational Medical Outcomes Partnership Common Data Model database. NLP model performance was assessed on a random subset of EHRs by comparing algorithm outputs to a physician-generated standard (using precision, recall, and their harmonic mean, or F1-score). Of the 3127 HF patients, 103 potentially had ATTR-CM (age 78 ± 9 years; male 55%; ejection fraction of 48% ± 16). The mean diagnostic delay between HF and ATTR-CM diagnosis was 1.8 years. Besides HF and cardiomyopathy-related phenotypes, the strongest cardiac predictor was atrial fibrillation (AF; 72% in ATTR-CM vs. 60% in non-ATTR-CM, P = 0.02), whereas the strongest non-cardiac predictor was carpal tunnel syndrome (21% in ATTR-CM vs. 3% in non-ATTR-CM, P < 0.001). The strongest combination predictor was AF, joint disorders, and HF with preserved ejection fraction (29% in ATTR-CM vs. 18% in non-ATTR-CM: odds ratio = 2.03, 95% confidence interval = 1.28-3.22)., Conclusions: Not only well-known variables associated with ATTR-CM but also unique combinations of cardiac and non-cardiac phenotypes are able to predict ATTR-CM in a real-world HF population, aiding in early identification of ATTR-CM patients., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The Cardiovascular Outcomes Retrospective Data analysIS in Heart Failure (CORDIS-HF) is a single-centre retrospective study aimed to (i) clinically characterize a real-world population with heart failure (HF) with reduced (HFrEF) and mildly reduced ejection fraction (HFmrEF), (ii) evaluate impact of renal-metabolic comorbidities on all-cause mortality and HF readmissions, and (iii) determine patients' eligibility for sodium-glucose cotransporter 2 inhibitors (SGLT2is)., Methods and Results: Using a natural language processing algorithm, clinical data of patients diagnosed with HFrEF or HFmrEF were retrospectively collected from 2014 to 2018. Mortality and HF readmission events were collected during subsequent 1 and 2 year follow-up periods. The predictive role of patients' baseline characteristics for outcomes of interest was assessed using univariate and multivariate Cox proportional hazard models. Kaplan-Meier analysis was used to determine if type 2 diabetes (T2D) and chronic kidney disease (CKD) impacted mortality and HF readmission rates. The European SGLT2i label criteria were used to assess patients' eligibility. The CORDIS-HF included 1333 HF patients with left ventricular ejection fraction (LVEF) < 50% (413 HFmrEF and 920 HFrEF), who were predominantly male (69%) with a mean [standard deviation (SD)] age of 74.7 (12.3) years. About one-half (57%) of patients presented CKD and 37% T2D. The use of guideline-directed medical therapy (GDMT) was high (76-90%). HFrEF patients presented lower age [mean (SD): 73.8 (12.4) vs. 76.7 (11.6) years, P < 0.05], higher incidence of coronary artery disease (67% vs. 59%, P < 0.05), lower systolic blood pressure [mean (SD): 123 (22.6) vs. 133 (24.0) mmHg, P < 0.05], higher N-terminal pro-hormone brain natriuretic peptide (2720 vs. 1920 pg/mL, P < 0.05), and lower estimated glomerular filtration rate [mean (SD): 51.4 (23.3) vs. 54.1 (22.3) mL/min/1.73 m 2 , P < 0.05] than those with HFmrEF. No differences in T2D and CKD were detected. Despite optimal treatment, event rates for the composite endpoint of HF readmission and mortality were 13.7 and 8.4/100 patient years. The presence of T2D and CKD negatively impacted all-cause mortality [T2D: hazard ratio (HR) = 1.49, P < 0.01; CKD: HR = 2.05, P < 0.001] and hospital readmission events in all patients with HF. Eligibility for SGLT2is dapagliflozin and empagliflozin was 86.5% (n = 1153) and 97.9% (n = 1305) of the study population, respectively., Conclusions: This study identified high residual risk for all-cause mortality and hospital readmission in real-world HF patients with LVEF < 50% despite GDMT. T2D and CKD aggravated the risk for these endpoints, indicating the intertwinement of HF with CKD and T2D. SGLT2i treatment that clinically benefits these different disease conditions can be an important driver to lower mortality and hospitalizations in this HF population., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Serial transthoracic echocardiographic (TTE) assessment of LVEF and GLS are the gold standard in screening Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). Non-invasive left-ventricle (LV) pressure-strain loop (PSL) emerged as a novel method to quantify Myocardial Work (MW). This study aims to describe the temporal changes and longitudinal trajectories of MW indices during cardiotoxic treatment. We included 50 breast cancer patients with normal LV function referred for anthracycline therapy w/wo Trastuzumab. Medical therapy, clinical and echocardiographic data were recorded before and 3, 6, and 12 months after initiation of the chemotherapy. MW indices were calculated through PSL analysis. According to ESC guidelines, mild and moderated CTRCD was detected in 10 and 9 patients, respectively (20% CTRCD mild , 18% CTRCD mod ), while 31 patients remained free of CTRCD (62% CTRCD neg ). Prior to chemotherapy MWI, MWE and CW were significantly lower in CTRCD mod than in CTRCD neg and CTRCD mild . Overt cardiac dysfunction in CTRCD mod at 6 months was accompanied by significant worse values in MWI, MWE and WW compared to CTRCD neg and CTRCD mild . MW features such as low baseline CW, especially when associated with a rise in WW at follow-up, may identify patients at risk for CTRCD. Additional studies are needed to explore the role of MW in CRTCD.

Aims: Risk stratification in patients with a new onset or worsened heart failure (HF) is essential for clinical decision making. We have utilized a novel approach to enrich patient level prognostication using longitudinally gathered data to develop ML-based algorithms predicting all-cause 30, 90, 180, 360, and 720 day mortality., Methods and Results: In a cohort of 2449 HF patients hospitalized between 1 January 2011 and 31 December 2017, we utilized 422 parameters derived from 151 451 patient exams. They included clinical phenotyping, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions reflecting the standard of care as captured in individual electronic records. The development of predictive models consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets. ML models yielded area under the receiver operating characteristic curve (AUC-ROC) performance ranging from 0.83 to 0.89 on the outcome-balanced validation set in predicting all-cause mortality at aforementioned time-limits. The 1 year mortality prediction model recorded an AUC of 0.85. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC, and HFrEF 0.86 AUC, respectively. Model performance improved when utilizing data from more hospital contacts compared with only data collected at baseline., Conclusions: Our findings present a novel, patient-level, comprehensive ML-based algorithm for predicting all-cause mortality in new or worsened heart failure. Its robust performance across phenotypes throughout the longitudinal patient follow-up suggests its potential in point-of-care clinical risk stratification., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Preliminary studies have suggested a low post-vaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in heart transplant(HTx)recipients. Although many studies have focused on the role of antibodies in vaccine-induced protection against SARS-CoV-2, the role of T cell immunity is less well characterized. To date, data regarding seroconversion and T cell response after mRNA SARS-CoV-2 vaccination in patients undergoing HTx are scarce. Therefore, the present study aimed to assess the specific memory humoral and cellular responses after two doses of the BNT162b2 vaccine in HTx recipients. Methods: Blood was drawn from heart transplant (HTx) recipients at two pre-specified time points after the first and second vaccine doses to measure both the anti-SARS-CoV-2 antibody response against the spike protein and the SARS-CoV-2-reactive T cell response. Results: Our study included 34 SARS-CoV-2 naïve HTx recipients (mean age, 61 ± 11 years). The mean time from transplantation to the first vaccine dose is 10 ± 10 years. Subgroup analysis (n = 21) demonstrated that after the first vaccine dose, only 14% had antibodies and 19% had a SARS-CoV-2-reactive T-cell response, which increased to 41% and 53%, respectively, after the second dose. Interestingly, 20% of patients with no antibodies after the second dose still had a positive SARS-CoV-2-reactive T cell response. The percentage of patients with positive S-IgG antibody titers was significantly higher 5 years after transplantation (18% 0-5 years post-TX vs. 65% 5 years post-TX, p = 0.013). Similarly, 5 years after heart transplantation, the percentage of patients with a T cell response was significantly higher (35% 0-5 years post-TX vs. 71% 5 years post-TX, p = 0.030). Conclusions: In SARS-CoV-2 naïve HTx recipients, post-vaccination antibody titers but also SARS-CoV-2 specific T cell response are low. Therefore, the protection from SARS-CoV-2 that is generally attributed to vaccination should be regarded with caution in HTx recipients.