Ventricular Assist Device Implantation Research Articles

Curricular Self-management for patients on ventricular assist device support decreases depression: A multicenter randomized controlled trial.

Utilization of ventricular assist device (VAD) support in patients with end-stage heart failure is well advanced. Recent studies emphasize the need to develop and evaluate evidence-based psychosocial support interventions for patients following VAD implantation. A national, multi-center study in four established German heart centers was initiated. An evidence-based VAD curriculum was developed; a randomized controlled trial evaluated the impact of the interprofessional intervention over time. Primary combined endpoint was the occurrence of adverse events (thromboembolic events, driveline infections, bleeding, rehospitalization, and death); secondary endpoints were psychosocial outcomes (anxiety, depression [HADS], quality of life [QoLVAD], social support [FSoZu], and self-management [SELMA]). A total of 140 patients were randomized block-wise to intervention (IG n = 70) or control (CG n = 70). Center-effects were considered. Instruments were completed at four time points (T0-T3). At baseline, intervention group (IG) patients were 19% female (control group [CG] 19%; p = 0.982); 58 ± 11 years. (CG 58 ± 11 years.; p = 0.966); 80% were implanted electively (CG 79%; p = 0.968). No significant difference in primary endpoint was found between IG versus CG (p > 0.05). For secondary endpoints, mixed linear regression revealed a significant reduction in depression scores in IG compared to CG (est. 1.18; 95% CI -2.17 to -0.18; p = 0.021). Clinically significant reductions in anxiety were greater in IG patients between T0 and T3 (IG 51.9%; CG 40.7%); increased anxiety was reported in 3.7% IG (11.1% CG). Mixed linear regression analyses favored IG (all >0.05) for QoL, social support, and self-management. A comprehensive curricular VAD intervention has potential to decrease depression levels and improve psychosocial outcomes of patients on VAD support.

Stenting of outflow graft obstruction after left ventricular assist device implantation.

Stenting of outflow graft obstruction after left ventricular assist device implantation.

The Prognostic Role of Pulmonary Arterial Elastance in Patients Undergoing Left Ventricular Assist Device Implantation: A Pilot Study

Background: Pulmonary arterial elastance (Ea) is a helpful parameter to predict the risk of acute postoperative right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation. A new method for calculating Ea, obtained by the ratio between transpulmonary gradient and stroke volume (EaB), has been proposed as a more accurate measure than the Ea obtained as the ratio between pulmonary artery systolic pressure and stroke volume (EaC). However, the role of EaB in predicting acute RVF post-LVAD implantation remains unclear. Methods and Results: A total of 35 patients who underwent LVAD implantation from 2018 to 2021 were reviewed in this retrospective analysis. Acute RVF after LVAD implantation occurred in 12 patients (34%): 5 patients with moderate RVF (14% of total) and 7 patients with severe RVF. The EaB was not significantly different between the “severe RVF” vs. “not-severe RVF” groups (0.27 ± 0.04 vs 0.23 ± 0.1, p < 0.403). However, the combination of arterial elastance and central venous pressure was significantly different between the “not-severe RVF” group (central venous pressure < 14 mmHg and EaC < 0.88 mmHg/mL or EaB < 0.24 mmHg/mL; p < 0.005) and the “severe RVF” group (central venous pressure > 14 mmHg and EaC > 0.88 mmHg/mL or EaB > 0.24 mmHg/mL; p < 0.005). Conclusions: Ea is a reliable parameter of right ventricular afterload and helps discriminate the risk of acute RVF after LVAD implantation. The combined analysis of Ea and central venous pressure can also risk stratify patients undergoing LVAD implantation for the development of RVF.

Hospitalizations and cardiac sarcoidosis: insights into presentation and diagnosis from the nationwide readmission database.

Cardiac sarcoidosis (CS) is an increasingly recognized cause of cardiac disease. Because the clinical presentation of CS is non-specific, the diagnosis is often delayed. Early detection is essential to initiate treatments that reduce the risk of heart failure (HF) and arrhythmic death. We therefore aimed to describe the features of CS hospitalizations during which the initial diagnosis of CS is made. We performed a retrospective analysis of hospitalizations from 2016 to 2019 in the Nationwide Readmission Database (NRD). Hospitalizations with a primary diagnosis suggestive of CS (HF/cardiomyopathy, cardiac arrest, arrhythmias, or heart block) were categorized into cases with and without CS as a secondary diagnosis (CS+ and CS-, respectively). One-to-one propensity score matching (PSM) was performed. The CS+ cohort comprised 1,146 hospitalizations and the CS- cohort 3,250,696 hospitalizations. The CS+ cohort included patients who were younger and more often male. PSM resulted in highly matched cohorts (absolute standardized mean difference <0.1). Primary diagnoses of ventricular arrhythmias (VA) or heart block were more frequent in matched CS+ hospitalizations, whereas primary diagnosis of HF/cardiomyopathy was more frequent in matched CS- hospitalizations. The matched CS+ group exhibited higher rates of in-hospital procedures and longer length of stay. In-hospital mortality and 30-day readmission were similar between matched cohorts. These findings highlight increased rates of CS in younger males with primary diagnoses of VA and heart block, and increased use of diagnostic and therapeutic interventions such as pacemaker and left ventricular assist device implantation, and could aid clinicians in more timely diagnosis and treatment of CS.

Abstract 4124267: Comparison of Right Ventricular Failure Prediction Models to Predict Right Ventricular Assist Device (RVAD) After HeartMate3 Implantation

Introduction: The requirement for right ventricular-assisted device (RVAD) implantation portends poor outcomes after left ventricular-assisted device (LVAD) implantation. We investigate RVF prediction models to help prediction of RV failure requiring RVAD implantation after centrifugal-flow LVAD HeartMate3 (HM3) placement. Methods: A total of 124 patients who underwent HM3 implantation at our institution from 2015-2023 were included in our analysis. We collected clinical variables used in EUROMACS RVF Risk Score (Circulation 2018), Utah Model (Am J Cardiology 2010), Michigan RVF Risk Score (JACC 2008), and CRITT (ATS 2013). Baseline scoring systems were compared with our cohort of patients with and without RVAD implantation after HM3 placement with ROC Area Under the Curve (AUC) statistical analysis. In addition, we investigated the pulmonary artery pulsatility index (PAPi) as a predictor for RV failure requiring RVAD. Results: There were 17 patients (13.7%) who underwent RVAD implantation after HM3 placement. Patients who required RVAD implant had worse survival (p = 0.037). The EUROMACS score differentiated those patients who required RVAD from those who did not (AUC: 0.66; 95% C.I: 0.51-0.81). In contrast, CRITT (AUC: 0.64; 95% C.I: 0.49-0.78), Michigan score (AUC: 0.37; 95% C.I: 0.25-0.51), and Utah (AUC: 0.53; 95% C.I: 0.40-0.68) scores did not differentiate those who required RVAD. PAPi was significantly lower in patients requiring RVAD (2.5±1.2 vs 3.9±3.0, p=0.001). Also, even as a single parameter, PAPi had an AUC of 0.63 (95% C.I: 0.50-0.76). Conclusion: RVAD implantation is associated with high early mortality. Existing RVF prediction models were not able to predict future RVAD requirements with high AUC, with the EUROMACS system having the only statistical significance. There is a lack of a strong predictive model for RV failure in HM3. Future efforts are needed to establish predictors for RV failure requiring RVAD implants in the HM3 population, especially utilizing novel hemodynamic markers such as PAPi.

Abstract 4118949: Factors Influencing Left Ventricular Function Recovery Following Left Ventricular Assist Device Implantation in Pediatric Dilated Cardiomyopathy: Insights from Single-Cell RNA Sequencing Analysis

Background and Objective: Heart transplantation is a recognized treatment for pediatric severe heart failure, but long-term issues necessitate alternative treatments. Some dilated cardiomyopathy (DCM) cases show left ventricular function recovery after LVAD implantation. This occurrence could lead to new treatments, but mechanisms are unclear. This study explores preoperative molecular factors interacting with LVAD's effects using single-cell transcriptomics on clinical samples. Methods: Twenty-five pediatric DCM patients underwent Berlin Heart EXCOR (BHE) implantation at our institution since 2013. Those with left ventricular ejection fraction (LVEF) improving by &gt;20% were in the Recovery group (R), others in Non-Recovery (NR). Single-cell RNA-sequence was performed on myocardial tissue from six patients (three per group). Differential gene expression and pathway analysis were conducted for each cell type. Findings were validated by comparing them with histological evaluation or clinical examination in all 25 cases. Results: R: 10 patients; NR: 15. R's weight was 6.3 kg, NR's 9.9 kg (p=0.049); LVEF: R 23%, NR 16.5% (p=0.61). In pseudobulk analysis of cardiomyocytes, upregulated genes in R included NPPB, MYL7, PCDH9. KEGG analysis indicated activation of Tight Junction and ECM receptor pathways in R. In fibroblasts, major extracellular matrix proteins were higher in R, GSL gene expression in NR. Plasma Brain Natriuretic Peptide (BNP) at BHE implantation was significantly higher in R; 2913 [1836-3990 (95% CI)] vs 1278 [667-1888] pg/ml (Image1,2). No differences in tissue fibrosis rates were found between the groups. Conclusion: Alterations in gene expression patterns in some cell clusters, including cardiomyocytes, may contribute to left ventricular function recovery post-BHE implantation in pediatric DCM patients. Plasma BNP levels correlated with gene expression alterations, suggesting both a potentially protective effect on cardiomyocytes and a useful marker of LV functional recovery. Further validation of these candidate genes may elucidate intracellular molecular mechanisms.

Abstract 4138583: Incidence and Outcomes of Heparin-Induced Thrombocytopenia Among Patients Undergoing Left Ventricular Assist Device Implantation

Background: Left Ventricular Assist Devices (LVAD) are being increasingly used as a bridge to transplant and destination therapy for advanced (stage D) heart failure. Heparin-induced thrombocytopenia (HIT) increases the risk of thromboembolic and bleeding events. HIT is also a well-known complication in patients undergoing LVAD implantation. This study examines the incidence and impact of HIT on outcomes in LVAD implants using a nationwide database from 2016 to 2020. Methods: We queried the National Inpatient Sample database for 2016-2020 to identify all adults ≥ 18 who underwent LVAD insertion using ICD 10 codes. LVAD recipients were dichotomized into two cohorts by the presence of HIT. Our primary outcome was in-hospital mortality. Secondary outcomes included vascular complications, acute kidney injury (AKI), length of stay, and total cost. Outcomes were adjusted for demographic variables, hospital-level characteristics, and comorbidities using regression analysis. Results: A total of 19975 (95% CI: 18328 - 21622) hospitalization records for LVAD insertion were identified, out of which HIT occurred in 1.8%. There were significant differences in AKI requiring dialysis, (p &lt; 0.03) cardiogenic shock, (p&lt;0.01), mechanical ventilation (p&lt;0.01), pulmonary embolism (PE) (p&lt; 0.001) and acute deep vein thrombosis (DVT) (p&lt; 0.001) which occurred more in HIT. In-hospital mortality was not significantly associated with HIT (adjusted odds ratio [aOR] 1.49, 95% CI :0.73-3.04, p value 0.28). Older age (aOR 1.02; 95% CI: 1.01-1.02) was associated with mortality after LVAD insertion. AKI, ischemic stroke, hemorrhagic stroke, acute coronary syndrome, arterial dissection, cardiogenic shock, and mechanical ventilation were significantly associated with in-hospital mortality. Our analysis did not show any differences in the incidence of vascular complications, stroke, intraoperative bleeding, blood transfusions and AKI between the HIT and non-HIT group. The HIT group stayed longer in the hospital 39 days (95% CI: 36- 38) vs 37 days (95% CI: 35- 44) and incurred higher total hospital cost of $1,101,638 vs. $1,245,616) although this was not statistically significant. Conclusion: Among US hospitalized patients undergoing LVAD implants, HIT was significantly associated with a higher risk of AKI requiring dialysis, PE, acute DVT, cardiogenic shock and need for mechanical ventilation. It was however not associated with a higher risk of in-hospital mortality.

Interventional therapies for chronic heart failure: An overview of recent developments.

Heart failure (HF), the final manifestation of most cardiovascular diseases, has become a major global health concern, affecting millions of individuals. Despite basic drug treatments, patients present with high morbidity and mortality rates. However, recent advancements in interventional therapy have shown promising results in improving the prognosis of patients with HF. These advancements include transcatheter aortic valve replacement for severe aortic stenosis, transcatheter mitral valve repair for chronic mitral regurgitation, neuromodulation therapy for multiple targets and measures in the treatment of chronic HF and left ventricular assist device implantation for advanced HF (Figure 1). In this review, we aimed to provide an overview of the current progress in interventional therapies for chronic HF.

Commentator Discussion: Late follow-up for a randomized trial of surgical treatment of tricuspid valve regurgitation in patients undergoing left ventricular assist device implantation

Commentator Discussion: Late follow-up for a randomized trial of surgical treatment of tricuspid valve regurgitation in patients undergoing left ventricular assist device implantation

Predictive Accuracy of HeartMate 3 Risk Score After the Heart Transplant Allocation Change.

The HeartMate 3 risk score (HM3RS) was developed from the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) clinical trial to predict 1 and 2 year mortality after left ventricular assist device implantation. However, it has not been validated in a real-world population, especially after the heart transplant allocation system change on October 18, 2018. In this multicenter retrospective analysis, we found that HM3RS did not predict 1 and 2 year outcomes in the contemporary era, highlighting the need to revise this risk prediction tool in the real-world setting.

Perioperative Stroke Following Implantation of Left Ventricular Assist Device: A Retrospective Cohort Study

Perioperative Stroke Following Implantation of Left Ventricular Assist Device: A Retrospective Cohort Study

Minimally Invasive Video-Assisted Surgery for Concomitant Ascending Aorta and Aortic Valve Replacement via Right Infra-Axillary Thoracotomy.

This study aims to assess the safety, efficacy, and esthetic outcomes of an innovative 4 cm right infra-axillary incision approach for concomitant ascending aorta and aortic valve replacement (AAR and AVR), with a specific focus on achieving optimal surgical outcomes while ensuring minimal visible scarring. We retrospectively examined all elective cases of concomitant AAR and AVR surgery performed at our institution from July 2021 to June 2023. Exclusions encompassed emergency surgery, acute type A aortic dissection, active aortic valve endocarditis, redo cardiac surgery, the necessity for concurrent mitral valve replacement, or left ventricular assist device implantation. We collected and analyzed perioperative data for the patients. The study comprised 24 consecutive patients. Cardiopulmonary bypass time and aortic cross-clamp time averaged 215.0 (interquartile range [IQR], 38.0) and 158.0 (IQR, 37.0) min, respectively. No instances of reoperation due to postoperative bleeding or need for permanent pacemaker implantation were recorded. Initial 24-h postoperative drainage volume averaged 186.9 ± 76.9 mL. Average follow-up duration was 21.7 ± 6.2 months (range, 5 to 30 months). Throughout short-term follow-up, no occurrences of valve dysfunction, paravalvular leak, cardiovascular events necessitating readmission, or mortality were observed. The right infra-axillary incision approach effectively yields secure, successful, and cosmetically pleasing outcomes for concomitant AAR and AVR. Further research and comparisons are warranted to validate these findings.

Commentator Discussion: Simultaneous sternal-sparing durable left ventricular assist device implantation with aortic and mitral valve procedures

Commentator Discussion: Simultaneous sternal-sparing durable left ventricular assist device implantation with aortic and mitral valve procedures

Metabolic Consequences of Advanced Chronic Heart Failure and its Modification by Implantation of a Durable Left Ventricular Assist Device.

Heart failure (HF) is a clinical syndrome characterized by the inability of the heart to provide adequate perfusion to tissues and organs, resulting in typical symptoms such as fatigue, dyspnea, dyspepsia, or swelling due to decreased cardiac output. With its increasing prevalence, heart failure has become one of the leading causes of morbidity and mortality worldwide, imposing a significant burden on the population by reducing long-term life expectancy and raising hospital costs. Indeed, over 20 million people worldwide suffer from heart failure, with a 5-year mortality rate of 60-70%. As heart failure progresses, various structural and metabolic changes occur within the myocardium and organ systems. In the past two decades, therapeutic options for heart failure patients have significantly expanded. In addition to novel pharmacological treatment, advanced surgical methods such as heart transplantation (HTx) and the implantation of durable left ventricular assist devices (LVADs) are available for patients with end-stage heart failure. This review discusses the pathophysiological aspects and metabolic consequences of heart failure and metabolic changes, as well as the benefits and challenges of implanting a left ventricular assist device. Furthermore, future targets for heart failure diagnostics and therapy will be highlighted.

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.

Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF. We included 81 patients with stage D HF (ICM, n=44; DCM, n=37) undergoing left ventricular assist device implantation (n=59) or heart transplantation (n=22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation. Patients with ICM or DCM did not differ regarding age (61.5±5.7 vs. 56.5±12.7years, P=0.164), sex (86% vs. 84% male, P=0.725), type 2 diabetes mellitus (34% vs. 18%, P=0.126) or chronic kidney disease (8% vs. 11%, P=0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6±41.4 vs. 141.9±59.9pmol/(s*mg), P=0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59±0.28 vs. 0.69±0.36pmol/(s*ml), P=0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6±164.1 vs. 503.0±198.5nmol/min/mg protein, P=0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P=0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r=-0.296, P=0.019). Fibrosis was more prevalent in ICM (20.9±21.2 vs. 7.2±5.6% of area, P=0.002), but not associated with oxidative capacity (r=-0.13, P=0.327). More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.

Proteomics-based computational modelling of myocardial metabolism for personalized phenotyping and outcome prediction in advanced heart failure

Abstract Background Perturbations of myocardial metabolism and energy depletion are well-established hallmarks of heart failure (HF), yet methods for their systematic assessment remain limited in humans [1]. Computational modelling of the heart of individual patients represents an emerging precision medicine approach for personalized diagnosis of specific disease mechanisms and tailored clinical decision-making [2,3]. Purpose To determine the ability of computational modelling of patient-specific myocardial metabolism to assess individual bioenergetic phenotypes and their prognostic implications in HF. Methods Based on proteomics-derived enzyme intensity profiles in cardiac biopsies, we recently developed a computational model of myocardial metabolism capturing all pathways along energy-delivering substrates are processed to generate ATP [4]. Using this framework, we studied the individual energetic state in 17 sex-matched nonfailing controls and 48 patients with advanced HF (LVEF 20±10%, 72.9% non-ischemic aetiology, 52.1% females, 29.8% diabetics) undergoing heart transplantation (n=25) or ventricular assist device (VAD) implantation (n=23). The bioenergetic impact of alterations in substrate availability and myocardial workload were simulated, and the model’s ability to predict myocardial reverse remodelling after VAD implantation was assessed. Results Compared to controls, HF patients had a reduced ATP production capacity (p&amp;lt;0.01), although there was considerable interindividual variance, ranging from severely decreased to normal values. While overall oxygen consumption was lower in failing hearts, the amount of ATP generated per mole of oxygen did not differ (p=0.16). Maximum uptake capacity of fatty acids, glucose, and amino acids was comparable. By contrast, maximum uptake capacity of ketone bodies and lactate was reduced in the failing heart (p for both &amp;lt;0.05). There was a shift from fatty acid to glucose utilization in most HF patients, depending on substrate availability and myocardial workload. The ratio of fatty acid to glucose oxidation distinguished patients with LVEF recovery &amp;gt;10% after VAD implantation (C-index 0.93, p&amp;lt;0.01; Picture 1B) and correlated significantly with improvement in post-operative LVEF (r=0.67, p&amp;lt;0.01). ATP production capacity was not associated with reverse remodelling after VAD implantation. Conclusions Computational modelling identified a subset of advanced HF patients with preserved myocardial metabolism despite a similar degree of systolic dysfunction. Myocardial substrate preference but not ATP production capacity was associated with myocardial recovery after VAD implantation, which suggests a potential for substrate manipulation as a therapeutic approach in those with deranged fuel use. Computational assessment of myocardial metabolism in HF may improve understanding of disease heterogeneity, individual risk stratification, and guidance of personalized clinical decision-making in the future.

Ventricular assist devices as bridge to heart transplantation: minimally invasive approach with axial pumps vs sternotomy approach with centrifugal pumps: short term results

Abstract Introduction Microaxial flow ventricular assist devices (VADs) with hybrid approach could provide an advantage over centrifugal flow VADs with surgical implantation via median sternotomy as bridge to heart transplantation. Purpose We aimed to compare short-term results in intensive cardiac care unit between both groups. Methods Single-center retrospective registry comparing patients supported with microaxial flow VADs with hybrid approach (Impella 5.0 or 5.5) and surgical centrifugal flow VADs (biventricular or left univentricular CentriMag) as bridge to heart transplantation. Results Including 12 patients (January 2020-March 2022), 7 patients in hybrid approach group (2 patients with Impella 5.0-16,7% and 5 patients with Impella 5.5-41,7%) and 5 pacientes in sternotomy approach group (33.3% biventricular support and 8.3% left ventricular support). In first 48 hours after VAD implantation, worsening of renal function was greater in sternotomy approach group (Cr 2.23±0.88, 1.07±0.58;p=0.021) and there was a trend toward lower hemoglobin values (7.72±0.19, 8.9±1.35;p =0.059), with no differences in other analyzed variables (Table). A trend toward earlier respiratory weaning was observed in hybrid approach group (median 12 vs 48 hours,p=0.067). Sternotomy approach group required more frequent use of continuous renal replacement therapy (60% vs 0%,p=0.045). There were statistically non-significant differences in need for blood products or surgical reinterventions, although percentage of red blood cells transfused in first 48 hours after VAD implantation were lower in hybrid approach group than sternotomy approach group (median 4 (1.5-8) versus 8(2.5-13.5) in sternotomy approach group, p=0.309). The most common complication in sternotomy approach group was tamponade (80%- 4 patients versus 0 patients in hybrid approach) and in hybrid approach group access-related infections (28.57%, 2 patients). Ten patients received a transplant, one died for non-cardiovascular cause, and another underwent the implantation of long term VAD as bridge to transplantation. There were no differences in time from assistance implantation to heart transplantation. The most common complication after heart transplantation was primary graft failure in both groups (40%,2 patients) with no differences in mortality. Conclusions Microxial flow VADs with hybrid approach provide adequate support, with less need for continuous renal replacement therapy and shorter duration of mechanical ventilation after VAD implantation to admission in intensive cardiac care unit, a trend towards lower rates of reintervention due to bleeding was observed. The advantages of minimally invasive approach could increase its use as bridge to heart transplantation compared to VADs with sternotomy approach although small sample size may negatively influence the failure to reach statistical significance, and more studies are necessary to validate our preliminary experience.Variables analyzed 48 hours of admission

ABLE-SCORE: a simplified risk score for major adverse cardiovascular outcomes in patients with left ventricular noncompaction

Abstract Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with life-threatening complications and variable prognosis [1,2]. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVNC is comparatively complex for clinical practice [3,4]. Purpose To develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVNC. Methods This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVNC patients between January 2009 and December 2020 at a single national-level medical center (derivation cohort n=300; internal validation cohort n=129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort n=95). The derivation/internal validation cohorts and the multicenter external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors for MACE in the multivariable Cox regression predictive model, and underwent both internal and external validation to confirm its discrimination (Harrell’s C-index), calibration (calibration plots), and clinical applicability (decision curve analysis). Results A total of 524 LVNC patients (43.5 ± 16.6 years, 65.8% male) were included in the study. At the end of the follow-up, 97 (32.3%), 38 (29.5%), and 20 (21.1%) individuals in the derivation, internal validation, and external validation cohort experienced at least one endpoint of MACE. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement and left ventricular ejection fraction≤40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell’s C-index of 0.821 (95%CI 0.772-0.869), 0.786 (95%CI 0.703-0.869), and 0.750 (95%CI 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVNC. According to decision curve analysis, the ABLE-SCORE displayed greater net benefit than the currently existing risk score for MACE in LVNC [3], indicating its strength in clinical applicability. Conclusions Derived from readily available laboratory and echocardiographic variables, a simplified and efficient risk score for MACE was developed and validated using a large LVNC cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVNC.Development of the ABLE-SCOREValidation of the ABLE-SCORE

Impact of digoxin on gastrointestinal bleeding following left ventricular assist device implantation: a systematic review and meta-analysis

Abstract Introduction Gastrointestinal bleeding (GIB) is a common complication post Left Ventricular Assist Device (LVAD) implantation for patients with advanced heart failure. Recent observational evidence suggested a potential association of digoxin use and GIB reduction post LVAD; however, the proposed benefit remains uncertain. Therefore, we conducted a systematic review and meta-analysis to assess the impact of digoxin use on GIB post LVAD. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the studies published in English exploring GIB with chronic digoxin use following LVAD implantation, till 15/01/2024. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The primary outcome was all-cause GIB associated with digoxin use in comparison to non-digoxin use. Heterogeneity was assessed using Q test and I2, with I2 &amp;gt; 50% indicating marked heterogeneity. Results A total of three peer-reviewed observational studies (n= 14277) were included in the analysis of the primary outcome. More than 50% of patients received ACE inhibitors/angiotensin receptor blockers. Digoxin use post LVAD was associated with similar GIB incidence in comparison to non-digoxin use (Odds Ratio [OR]= 0.61; 95% CI, 0.33-1.14, I2= 81%, P=0.12), as shown in Figure 1. Interestingly, one study of 199 recipients of LVAD reported significantly lower gastrointestinal angiodysplasia-induced GIB with digoxin use (3% versus 13%, P=0.039). Conclusion Among patients with advanced HF requiring LVAD implantation, the use of digoxin demonstrated similar effectiveness of GIB prevention compared to non-digoxin use. Future studies needed to explore the potential use of digoxin for gastrointestinal angiodysplasia-induced GIB.Figure 1.Forest plot of gastrointestina

Prevalence, mechanisms and prognostic impact of dynamic mitral regurgitation unmasked by handgrip exercise in patients with hypokinetic non-dilated and dilated cardiomyopathy

Abstract Background Recent studies suggest that mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular (LV) remodeling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the hemodynamic relevance of MR and is recommended by current guidelines. Handgrip exercise may serve as alternative exercise intervention to bicycle exercise, as it is easy to perform even bedside. However, there are no data yet, on the prevalence, mechanisms and prognostic impact of dynamic MR in patients with dilated cardiomyopathy using isometric exercise testing. Aims We aimed to assess the prevalence, hemodynamic consequences, and prognostic impact of exercise-induced changes in MR in patients with hypokinetic non-dilated and dilated cardiomyopathy. Methods Patients with hypokinetic non-dilated and dilated cardiomyopathy and at least mild MR who underwent handgrip echocardiography at the University Hospital Duesseldorf between January 2018 and September 2021 were enrolled.Patients were followed-up for one year to assess clinical outcomes. We assessed all-cause mortality, HF-associated hospitalizations, MV surgery, transcatheter edge-to-edge repair (TEER), left ventricular assist device implantation and heart transplantation during follow-up. Results Fifty-eight patients were included (mean age 70±15 years; 41% female; mean LVEF 37±10%). At rest, 28 patients (48%) presented with mild MR, and 30 patients (52%) had moderate MR. Fifteen patients (26%) with non-severe MR at rest, developed dynamic severe MR during handgrip exercise. Patients with dynamic severe MR had advanced MR at rest, larger left atrial dimensions, and increased mitral annulus diameter (all p&amp;lt;0.01). During exercise, LVEDVi, LVESVi and parameters of local left ventricular remodeling (tenting height, tenting area) were increased in patients with dynamic severe MR compared to those with non-severe MR (all p&amp;lt;0.05). During one-year follow-up, there was no difference regarding all-cause mortality and HF hospitalizations in patients with dynamic severe MR and non-severe MR (Log-rank test Chi2 0.262; p=0.609)(Figure 1). However, patients with dynamic severe MR more often underwent mitral valve surgery/intervention than patients with non-severe MR (Log-rank test Chi2 29.41; p&amp;lt;0.001)(Figure 1). Conclusion Our results demonstrate that the evaluation of non-ischemic MR only at rest underestimates the full severity of the lesion. Handgrip exercise unmasks severe MR in every fourth patient with non-severe MR at rest. These data may have implications for therapeutic decision-making in symptomatic patients with hypokinetic non-dilated and dilated cardiomyopathy and non-severe MR at rest. TEER might present an effective treatment option to improve clinical outcomes in patients with non-ischemic cardiomyopathy and non-severe MR at rest but dynamic severe MR during exercise.Figure 1