Association of Plasma Creatinine Phosphokinase Elevation and a History of Idiopathic Cardiomyopathy in Recipients of Heart Transplant.

Plasma creatinine phosphokinase (CPK) elevation is frequent after heart transplantation. In the present study, we tested the hypothesis that this CPK elevation is related to idiopathic cardiomyopathy as primary cardiac disease. We included 203 patients who survived >1 year after heart transplantation. Plasma CPK was measured every 4 months during a 15.1 ± 7.7-year follow-up. In univariate analysis, CPK elevation was significantly associated with age at transplantation, length of follow-up, treatment with everolimus, and idiopathic cardiomyopathy as primary cardiac disease. In multivariate analysis, idiopathic cardiomyopathy and length of follow-up were the only significant predictors of CPK elevation (p = 0.002 and p = 0.0001, respectively). A subgroup of 19 patients had frequent CPK elevation (>20% of the dosages). All these patients but 1 had an idiopathic cardiomyopathy as primary disease. In 5 of these 19 patients, we identified a syndrome known to affect both cardiac and skeletal muscles. In conclusion, underlying idiopathic cardiomyopathy is a major determinant of plasma CPK elevation after heart transplantation. Our results show that besides well-described syndromes associating skeletal and cardiac muscle disease, idiopathic cardiomyopathy may be associated with subclinical skeletal muscle myopathy.

Mitral valve repair is better than mitral valve replacement in native mitral valve endocarditis: Results from a prospective matched cohort.

BACKGROUND: In native mitral valve infective endocarditis (NMIE), the respective values of mitral valve repair (MVRep) and replacement (MVR) are still debated. AIM: To compare MVRep and MVR in a large prospective matched cohort. METHODS: Between 2010 and 2017, all consecutive patients operated on for NMIE in our centre were included prospectively. Clinical and outcome features were compared between the two groups. Primary endpoint was event-free survival, including death, reoperation and relapse. Univariate and multivariable survival analyses and a propensity score analysis were performed. RESULTS: Among 152 patients, 115 (75.7%) underwent MVRep, and 37 (24.3%) MVR. Median follow-up was 28±22months. Surgery was performed during the active phase in 75.0% of patients (25.7% on an urgent basis). Compared with the MVRep group, patients in the MVR group were more frequently intravenous drug abusers (10.8% vs. 0.9%; P=0.016), had a more frequent history of rheumatic fever (13.5% vs. 0%; P=0.001), more aortic abscesses (16.7% vs. 3.5%; P=0.018), larger vegetations (16.6±8.1mm vs. 12.6±9.9mm; P=0.042) and poorer New York Heart Association status (P=0.006). Overall mortality was lower in the MVRep group than in MVR group (11.3% vs. 29.3%; P=0.018). Event-free survival was better in the MVRep group than in the MVR group in univariate analysis (hazard ratio: 2.72, 95% confidence interval: 1.34-5.52; P=0.004). Survival analysis in the propensity-matched cohort showed that MVRep was safer than MVR (log rank test: P=0.018). Multivariable analysis using the Cox proportional hazard model confirmed this finding (hazard ratio: 3.48, 95% confidence interval: 1.15-10.61; P=0.03). CONCLUSIONS: MVRep is feasible in most cases of NMIE and, when technically possible, should be preferred, even in urgent surgery.

Cardiac Manifestations in Patients with COVID-19: A Scoping Review.

Background: Coronavirus disease 2019 (COVID-19), commonly affects the lungs, but the involvement of other organs, particularly the heart, is highly prevalent as has been reported in several studies. The overall aim of this review was to provide an in-depth description of the available literature related to the cardiac system and COVID-19 infection. It focuses on type and the frequency of cardiac manifestations, clinical parameters and cardiac biomarkers that support the prognosis of COVID-19 patients, and the cardiac adverse events and outcomes related to pharmacotherapy. Methods: A scoping review was conducted searching Embase, PubMed, Epistomonikos, Medrxiv, BioRxiv databases, up to November 2020, for systematic reviews relevant to cardiac manifestations in adult COVID-19 patients. Relevant articles were screened and extracted to summarize key outcomes and findings. Results: A total of 63 systematic reviews met the inclusion criteria. The overall frequency of acute cardiac injury ranged from 15% to 33% in the reporting studies. The main cardiac complications were arrhythmias (3.1% to 6.9% in non-severe patients, 33.0% to 48.0% in severe disease), acute coronary syndromes (6% to 33% in severe disease), and myocarditis. Most studies found no association with the use of Renin-angiotensin-aldosterone system inhibitors (RAASI) with COVID-19 outcomes such as susceptibility to infection, hospitalization, severity, and mortality. Conclusion: This study provided an overview of the several cardiac complications associated with Covid-19. Cardiac injury, arrhythmias, myocarditis, cardiac failure, and acute coronary syndrome, are prevalent and clinically significant and associated with COVID-19 disease severity and mortality. Other studies are needed to clearly identify what is the part of viral heart infection and what is the part of cardiac injury secondary to acute respiratory failure and inflammation. In the therapeutic field, these systematic reviews gave heterogenous results. This underlines the importance of randomized trials to determine the right therapeutic approach.

Infective endocarditis with neurological complications: Delaying cardiac surgery is associated with worse outcome.

BACKGROUND: Infective endocarditis (IE) is associated with a high mortality rate, related in part to neurological complications. Studies suggest that valvular surgery should be performed early when indicated, but is often delayed by the presence of neurological complications. AIM: To assess the effect of delaying surgery in patients with IE and neurological complications and to identify factors predictive of death. METHODS: In a prospective, single-centre study in a referral centre for IE, all patients with IE underwent systematic screening for neurological complications. The primary outcome was 6-month death. In patients presenting with neurological complications, the prognosis according to surgical status was analysed and a Cox regression model used to identify variables predictive of death. RESULTS: Between April 2014 and January 2018, 351 patients with a definite diagnosis of left-sided IE were included. Ninety-four patients (26.8%) presented with at least one neurological complication. Fifty-nine patients (17.7%) died during 6-month follow-up. Six-month mortality rates did not differ significantly between patients with and without neurological complications (P=0.60). Forty patients had a temporary surgical contraindication because of neurological complications. During the period of surgical contraindication, seven of these patients (17.5%) died, six (15.0%) presented a new embolic event, and 12 (30.0%) presented cardiac or septic deterioration. In multivariable analysis, predictive factors of death in patients presenting with neurological complications were temporary surgical contraindication (hazard ratio 7.36, 95% confidence interval 1.61-33.67; P=0.010) and presence of a mechanical prosthetic valve (hazard ratio 16.40, 95% confidence interval 2.22-121.17; P=0.006). CONCLUSIONS: Patients with a temporary surgical contraindication due to neurological complications had a higher risk of death and frequent major complications while waiting for surgery. When indicated, the decision to postpone surgery in the early phase should be weighed against the risk of infectious or cardiac deterioration.

Infective endocarditis in patients with heart transplantation.

BACKGROUND: The incidence of nosocomial and health care-related infective endocarditis (IE) is increasing. Heart transplantation (HT) implies immunosuppression and frequent health care contact. Our aim was to describe the current profile and prognosis of IE in HT recipients. METHODS: Multicenter retrospective registry-based study in Spain and France that included cases between 2008 and 2019. RESULTS: During the study period, 8305 HT were performed in Spain and France. We identified 18 IE cases (rate 0.2%). Median age was 57 years; 12 were men (67%). Valve involvement did not have a predominant location and three patients (16.7%) had atrial or ventricular vegetations without valve involvement. The median age-adjusted Charlson index was 4 (interquartile range 3-5). Eleven IE cases (61%) were nosocomial/health care-related. Median time (range) between HT and development of IE was 43 months (interquartile range 6-104). The major pathogens were Staphylococcus sp. (n = 8, 44%), Enterococcus sp. (n = 4, 22%), and Aspergillus sp. (n = 3, 17%). Although eight patients (44%) had a surgical indication, it was only performed in three cases (17%). Three patients (17%) died during the first IE hospital admission. CONCLUSIONS: IE in HT recipients has specific characteristics. Valve involvement does not have a predominant location and non-valvular involvement is common. Three fifths have a nosocomial/health care-related origin. The major pathogens were staphylococci (44%), enterococci (22%), and Aspergillus (17%). In-hospital mortality was 17%.

Left atrial dysfunction as marker of poor outcome in patients with hypertrophic cardiomyopathy.

BACKGROUND: The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM). OBJECTIVE: To assess LA strain correlation with outcome in HCM. METHODS: A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54±17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed. RESULTS: Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II-III in 54%, and B-type natriuretic peptide (BNP) concentration was 199±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m2, PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s-1. In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤0.0004). At a mean follow-up of 21 (range 18-23) months, patients with adverse cardiac events (n=65) presented with more impaired LA function (all P ≤0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92-0.97, P<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008). CONCLUSIONS: The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated.

Glycosylated Hemoglobin as a Surrogate for the Prevention of Cardiovascular Events in Cardiovascular Outcome Trials Comparing New Antidiabetic Drugs to Placebo.

BACKGROUND AND OBJECTIVES: The value of glycosylated hemoglobin (HbA1c) as a surrogate marker for the prevention of cardiovascular outcomes on antidiabetic drugs is debated. The 2008 FDA guidance led to multiple large clinical trials to evaluate the effect of new antidiabetic drugs versus placebo on major adverse cardiac events (MACE). The aim of this study was to evaluate the relation between MACE and HbA1c decrease between antidiabetic drug and placebo across the spectrum of cardiovascular outcome trials (CVOT). METHODS: In this systematic review, we included randomized controlled trials that compared an antidiabetic drug to placebo in addition to current standard of care with the primary intention of demonstrating cardiovascular safety. We investigated the relationship between MACE decrease on antidiabetic drug and HbA1c reduction on antidiabetic drug using the coefficient correlation. We also studied the effects of potential confounders on MACE decrease. RESULTS: Fourteen eligible trials including 128,149 patients were included, 12,114 of whom experienced MACE. Mean achieved HbA1c absolute reductions on antidiabetic treatment versus placebo varied from 0.29 to 1%. The decrease of MACE on antidiabetic drug was significantly correlated with mean HbA1c reduction (r = 0.88, 95% CI: 0.67-0.96, p < 0.001) and weight loss (r = 0.81, 95% CI: 0.46-0.94, p < 0.001). In a bivariate model including weight loss, only HbA1c reduction remained significantly correlated with the decrease of MACE on antidiabetic drug (p = 0.019). CONCLUSION: Across CVOT, the decrease in MACE incidence on various antidiabetic drugs is significantly correlated with HbA1c reduction. This meta-analysis supports HbA1c as an appropriate surrogate endpoint for cardiovascular events. Our analysis supports that changes in HbA1c should be taken into account while interpreting effects of new antidiabetic drugs on cardiovascular outcomes.

Prognostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Infective Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the diagnosis of infective endocarditis (IE), but its prognostic value remains unknown. OBJECTIVES: This study sought to assess the prognostic value of 18F-FDG PET/CT in prosthetic valve endocarditis (PVE) and native valve endocarditis (NVE). METHODS: This study prospectively included 173 consecutive patients (109 PVE and 64 NVE) with definite left-sided IE who had an 18F-FDG PET/CT and were followed-up for 1 year. The primary endpoint was a composite of major cardiac events: death, recurrence of IE, acute cardiac failure, nonscheduled hospitalization for cardiovascular indication, and new embolic event. RESULTS: 18F-FDG PET/CT was positive in 100 (58%) patients, 83% (n = 90 of 109) in the PVE, and 16% (n = 10 of 64) in the NVE group. At a mean follow-up of 225 days (interquartile range: 199 to 251 days), the primary endpoint occurred in 94 (54%) patients: 63 (58%) in the PVE group and 31 (48%) in the NVE group. In the PVE group, positive 18F-FDG PET/CT was significantly associated with a higher rate of primary endpoint (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.1 to 6.7; p = 0.04). Moderate to intense 18F-FDG valvular uptake was also associated with worse outcome (HR: 2.3; 95% CI: 1.3 to 4.5; p = 0.03) and to new embolic events in PVE (HR: 7.5; 95% CI: 1.24 to 45.2; p = 0.03) and in NVE (HR: 8.8; 95% CI: 1.1 to 69.5; p = 0.02). In the NVE group, 18F-FDG PET/CT was not associated with occurrence of the primary endpoint CONCLUSIONS: In addition to its good diagnostic performance, 18F-FDG PET/CT is predictive of major cardiac events in PVE and new embolic events within the first year following IE.

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

BACKGROUND: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation. METHODS: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range]. RESULTS: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach. CONCLUSIONS: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.

Predictive value of achieved blood pressure for cardiac events in the long-term follow-up of heart transplant recipients.

BACKGROUND: A low diastolic blood pressure (DBP) is associated with increased cardiovascular events in patients with coronary artery disease or chronic kidney disease. AIM: The aim of this study was to assess the association of blood pressure with cardiac events during the long-term follow-up of heart transplant recipients. PATIENTS AND METHODS: In this prospective cohort study, we performed ambulatory blood pressure monitoring and home blood pressure monitoring in 76 transplant heart recipients 13.5±6.6 years after transplantation. The patients were followed for 54±17 months after blood pressure monitoring. RESULTS: Twenty-one patients had a cardiac event (cardiac death, acute coronary event, coronary revascularization procedure, and hospitalization for heart failure) during the follow-up. In the Kaplan-Meier survival analysis, we found that a DBP below the median value (<81 mmHg) was associated significantly with cardiac events (log-rank: P=0.01). In a multivariate model, plasma creatinine and left ventricular ejection fraction (LVEF), but not DBP, were associated significantly with cardiac events. Low DBP was associated significantly with LVEF less than 55% (P=0.004). CONCLUSION: A DBP below the median value predicts cardiac events during the long-term follow-up of heart transplant recipients, but is not an independent predictor. The association between low DBP and low LVEF explains at least in part the predictive value of low DBP.

Predictive value of E/A and E/E' Doppler indexes for cardiac events in heart transplant recipients.

BACKGROUND: Doppler-derived indexes associated with high left ventricular filling pressures are risk factors for cardiac events in various populations. The aim of this study was to evaluate the predictive value of two of these Doppler indexes during the long-term follow-up of heart transplantation. METHODS AND RESULTS: In this cohort study, we measured E/A ratio combining early filling velocity (E) with late filling velocity (A) and E/E' ratio combining E wave with relaxation velocity on tissue doppler (E') in 122 transplant heart recipients, 6.9±5.9 years after transplantation. The patients were followed for 97±32 months after Doppler measurements. We found an E/A>2 in 68 patients and an E/E'>15 in 23 patients. Forty patients had a cardiac event (cardiac death, retransplantation, acute coronary events, hospitalization for heart failure, treated acute rejection episodes, and coronary revascularization procedures) during the follow-up. In multivariate analysis, E/A and E/E' were significantly associated with cardiac events (hazard ratio 2.2, 95% CI: 1.1-4.4; P=.02 and hazard ratio 2.3, 95% CI: 1.1-4.8; P=.02, respectively). E/E', E/A, and significant coronary stenoses were the strongest predictors of cardiac events. CONCLUSIONS: E/A and E/E' Doppler indexes may be used to predict cardiac events during the long-term follow-up of heart transplant recipients.

Chronic heart failure in heart transplant recipients: Presenting features and outcome.

BACKGROUND: The ageing graft frequently shows coronary lesions and a restrictive physiology. AIMS: To determine the presenting features and outcome of chronic heart failure in heart transplant recipients. METHODS: In this cohort study, we compared 44 consecutive heart transplant recipients who developed chronic heart failure more than 1 year after heart transplantation with 44 control heart transplant recipients who did not develop heart failure. RESULTS: We found that patients who developed heart failure had more frequently a history of hypertension or diabetes before transplantation. During the 12 months after transplantation, significantly more patients had moderate-to-severe acute rejections (≥ grade 2R) in the heart failure group than in the control group. At the time of heart failure diagnosis, systolic left ventricular function was preserved in 50% of patients and coronary angiography was normal or near normal in 36% of patients. Half of the 44 patients in the heart failure group died within 2 years of heart failure diagnosis. Ascites and end-stage renal failure requiring dialysis were significantly more frequent during follow-up in the heart failure group than in the control group (respectively, 10/44 vs 0/44 [P=0.001] and 18/44 vs 5/44 [P=0.003]). CONCLUSION: In heart transplant recipients presenting with heart failure, systolic left ventricular function is frequently preserved and coronary angiography is frequently abnormal, but may be normal or near normal. During follow-up, the main features of these patients are a high mortality rate after heart failure diagnosis, a frequent need for renal dialysis and frequent ascites.

Plasma ultrasensitive cardiac troponin during long-term follow-up of heart transplant recipients.

BACKGROUND: Plasma troponin is a risk factor for cardiac events in various populations. We evaluated the determinants and predictive value of plasma cardiac troponin I (cTnI) during the long-term follow-up of heart transplantation. METHODS AND RESULTS: We prospectively measured cTnI in 100 heart transplant recipients, 13.0 ± 6.0 years after transplantation, during a routine visit including echocardiography and laboratory measurements. The patients were followed for 21.3 ± 4.9 months after this troponin measurement. cTnI ≥0.006 µg/L (detection threshold) was found in 37 of these 100 patients. Plasma troponin significantly increased with the presence and severity of coronary lesions detected by means of coronary angiography and was significantly associated with age, left ventricular mass, history of post-transplantation heart failure, body mass index, and plasma creatinine. Of 37 patients with cTnI ≥0.006 µg/L, 13 had a cardiac event during follow-up compared with 2 of 63 patients with cTnI <0.006 µg/L (P < .0001). The relation between cTnI and cardiac events remained significant in multivariate analysis. CONCLUSIONS: cTnI is frequently detectable during long-term follow-up after heart transplantation and is associated with chronic graft rejection and renal failure. A detectable cTnI may help identify heart transplant recipients at high risk of cardiac events.