Neonatal myocardial infarction: substantial improvement of cardiac function after autologous bone marrow-derived cell therapy

Clinical and genetic insights into non-compaction: a meta-analysis and systematic review on 7598 individuals Abstract Background Left ventricular non-compaction has been increasingly diagnosed in recent years. However, it is still debated whether non-compaction is a pathological condition or a physiological trait. In this meta-analysis and systematic review, we compare studies, which investigated these two different perspectives. Furthermore, we provide a comprehensive overview on the clinical outcome as well as genetic background of left ventricular non-compaction cardiomyopathy in adult patients. Methods and results We retrieved PubMed/Medline literatures in English language from 2000 to 19/09/2018 on clinical outcome and genotype of patients with non-compaction. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Altogether, 35 studies with 2271 non-compaction patients were included in our meta-analysis. The mean age at diagnosis was the mid of their fifth decade. Two-thirds of patients were male. Congenital heart diseases including atrial or ventricular septum defect or Ebstein anomaly were reported in 7% of patients. Twenty-four percent presented with family history of cardiomyopathy. The mean frequency of neuromuscular diseases was 5%. Heart rhythm abnormalities were reported frequently: conduction disease in 26%, supraventricular tachycardia in 17%, and sustained or non-sustained ventricular tachycardia in 18% of patients. Three important outcome measures were reported including systemic thromboembolic events with a mean frequency of 9%, heart transplantation with 4%, and adequate ICD therapy with 15%. Nine studies investigated the genetics of non-compaction cardiomyopathy. The most frequently mutated gene was TTN with a pooled frequency of 11%. The average frequency of MYH7 mutations was 9%, for MYBPC3 mutations 5%, and for CASQ2 and LDB3 3% each. TPM1, MIB1, ACTC1, and LMNA mutations had an average frequency of 2% each. Mutations in PLN, HCN4, TAZ, DTNA, TNNT2, and RBM20 were reported with a frequency of 1% each. We also summarized the results of eight studies investigating the non-compaction in altogether 5327 athletes, pregnant women, patients with sickle cell disease, as well as individuals from population-based cohorts, in which the presence of left ventricular hypertrabeculation ranged from 1.3 to 37%. Conclusion The summarized data indicate that non-compaction may lead to unfavorable outcome in different cardiomyopathy entities. The presence of key features in a multimodal diagnostic approach could distinguish between benign morphological trait and manifest cardiomyopathy.

Mean BMI, visit-to-visit BMI variability and BMI changes during follow-up in patients with acute myocardial infarction with systolic dysfunction and/or heart failure: insights from the High-Risk Myocardial Infarction Initiative Abstract Background In patients with acute myocardial infarction (MI), BMI < 18.5 kg/m2 and a decrease in BMI during follow-up have been associated with poor prognosis. For BMI ≥ 25 kg/m2, an “obesity paradox” has been suggested. Recently, high visit-to-visit BMI variability has also been associated with poor prognosis in patients with coronary artery disease. Aims To simultaneously evaluate several BMI measurements and study their association with cardiovascular (CV) outcomes in a large cohort of patients with acute myocardial infarction (MI) and left ventricular (LV) systolic dysfunction, heart failure (HF) or both. Methods The high-risk MI dataset is pooled from four trials: CAPRICORN, EPHESUS, OPTIMAAL and VALIANT. Mean BMI, change from baseline, and variability were assessed during follow-up. The primary outcome was CV death. Cox-proportional hazard models were performed to study the association between the various BMI parameters and outcomes (median follow-up = 1.8 years). Results A total of 12,719 patients were included (72% male, mean age 65 ± 11 years). Mean, change and visit-to-visit variability in BMI had a non-linear association with CV death (P < 0.001). Mean BMI < 26 kg/m2 (vs. ≥ 26–35 kg/m2) and BMI decrease during follow-up were independently associated with CV death (adjusted HR 1.32, 95% CI 1.16–1.51, P < 0.001 and adjusted HR 1.57, 95% CI 1.40–1.76, P < 0.001, respectively). Low and high BMI variability (< 2% and > 4%) were associated with increased event-rates, but lost statistical significance in sensitivity analysis including patients with ≥ 5 measurements or excluding patients with HF hospitalization, suggesting that BMI variability may be particularly associated with HF hospitalizations. Conclusion Mean BMI < 26 kg/m2 and a BMI decrease during follow-up were independently associated with CV death in patients with MI and LV systolic dysfunction, HF or both. These associations likely reflect poorer patient status and causality cannot be inferred.

Angiotensin-converting-enzyme inhibitors in hemodynamic congestion: a meta-analysis of early studies Abstract Aim Major clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in congestive heart failure (HF). Prior to these seminal findings hemodynamic effects of ACE inhibitors were examined in small studies. We aimed to review these studies systematically and meta-analyze the effects of ACE inhibitors on hemodynamics in HF. Methods and results We identified studies investigating the acute hemodynamic effect of ACE inhibitors in naïve patients with congestive heart failure by searching PubMed and the Cochrane Central Register of Controlled Trials. We extracted the changes in hemodynamic measures and their standard errors from study reports or calculated these values from baseline and post-medication measurements. Data were pooled using random effects models. In total, 41 studies with 46 independent cohorts consisting of 676 patients were included. ACE inhibitor treatment reduced pulmonary capillary wedge pressure by 7.3 (95% confidence interval 6.4–8.2) mmHg and right atrial pressure by 3.7 (95% confidence interval 1.3–6.1) mmHg in patients with HF. Cardiac index increased by 0.4 (95% confidence interval 0.2–0.6) ml/min/m2. Changes in hemodynamic measures were strongly connected to each other in weighted simple linear regression models. Conclusion Angiotensin-converting enzyme-inhibitors acutely reduced cardiac filling pressures and increased cardiac output in patients with congestive heart failure who were naïve for these drugs. These data indicate that ACE inhibitors exhibit a strong decongesting effect in congestive heart failure. In light of their impact on long-term prognosis, ACE inhibitors should also be considered as decongesting drugs in stable patients.

Does rhythm matter in acute heart failure? An insight from the British Society for Heart Failure National Audit Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with acute heart failure (AHF). The presence of AF is associated with adverse prognosis in patients with chronic heart failure (CHF) but little is known about its impact in AHF. Methods Data were collected between April 2007 and March 2013 across 185 (> 95%) hospitals in England and Wales from patients with a primary death or a discharge diagnosis of AHF. We investigated the association between the presence of AF and all-cause mortality during the index hospital admission, at 30 days and 1 year post-discharge. Results Of 96,593 patients admitted with AHF, 44,642 (46%) were in sinus rhythm (SR) and 51,951 (54%) in AF. Patients with AF were older (mean age 79.8 (79.7–80) versus 74.7 (74.5–74.7) years; p < 0.001), than those in SR. In a multivariable analysis, AF was independently associated with mortality at all time points, in hospital (HR 1.15, 95% CI 1.09–1.21, p < 0.0001), 30 days (HR 1.13, 95% CI 1.08–1.19, p < 0.0001), and 1 year (HR 1.09, 95% CI 1.05–1.12, p < 0.0001). In subgroup analyses, AF was independently associated with worse 30-day outcome irrespective of sex, ventricular phenotype and in all age groups except in those aged between 55 and 74 years. Conclusion AF is independently associated with adverse prognosis in AHF during admission and up to 1 year post-discharge. As the clinical burden of concomitant AF and AHF increases, further refinement in the detection, treatment and prevention of AF-related complications may have a role in improving patient outcomes.

Implementation of an intensified outpatient follow-up protocol improves outcomes in patients with ventricular assist devices Abstract Background Ventricular assist devices (VAD) are increasingly used as long-term treatment for advanced heart failure. However, survival after VAD implantation is still unsatisfactory, and no specific outpatient follow-up algorithms have been formally established. Here, we evaluate the effect of an intensified follow-up protocol (IFUP) on survival rates and VAD-associated complications. Methods and results This is a retrospective study of 57 patients who received a VAD at our center between February 2013 and December 2017. Inclusion criteria were discharge home after VAD implantation and follow-up in our VAD outpatient clinic. Patients implanted after October 2015 (n = 30) were monitored according to IFUP. This protocol embodied formalized, multi-disciplinary clinical visits every 4–8 weeks including a cardiologist, a cardiothoracic surgeon and a VAD-coordinator and was characterized by optimized anticoagulation and wound management as well as guideline-directed medical therapy. One-year survival in the IFUP patients was 97%, compared to 74% in the pre-IFUP era (p = 0.01). Implementation of IFUP was associated with a 90% risk-reduction for 1-year mortality (relative risk 0.099; p = 0.048). The rate of complications, e.g., device thrombosis and major bleeding, was significantly reduced, resulting in superior event-free survival in the IFUP group (p = 0.003). Furthermore, by implementation of IFUP, a more stable anticoagulation adjustment was achieved as well as an improved adherence to guideline-directed medical therapy. Conclusion Implementation of an IFUP for VAD patients is associated with a significant decrease in 1-year all-cause mortality. This emphasizes the need for more vigilance in the management of VAD patients by a dedicated multi-disciplinary team.

Epicardial fat accumulation is an independent marker of impaired heart rate recovery in obese patients with obstructive sleep apnea Abstract Background Sympathetic nervous system activation plays a pivotal role in obese patients with obstructive sleep apnea (OSA), contributing to increased cardiovascular risk. Epicardial adipose tissue (EAT) activates cardiac autonomic nervous system. Our main study objective was to investigate effects of these autonomic dysfunction factors on post-exercise heart rate recovery (HRR). Methods 36 patients, referred for clinical assessment of obesity (BMI > 30 kg/m2), underwent overnight polysomnography, transthoracic echocardiography and cardiopulmonary exercise testing. Results Compared to non-OSA patients, OSA patients were older and displayed reduced body weight-indexed peak VO2. Cardiac output at peak exercise was similar among groups. Peak exercise arterio-venous oxygen content difference D[a-v]O2 was lower in OSA patients. In univariate linear analysis, age, AHI, EAT thickness, peak VO2 and diabetes were associated with blunted HRR. Multiple linear regression analysis showed that increased EAT thickness, AHI and diabetes were independently associated with lower HRR. For identical AHI value and diabetes status, HRR significantly decreased by 61.7% for every 1 mm increase of EAT volume (p = 0.011). If HRR was treated as a categorical variable, EAT [odds ratio (OR) 1.78 (95% confidence interval [CI] 1.19–2.66); p = 0.005], and type 2 diabetes [OR 8.97 (95% CI 1.16–69.10); p = 0.035] were the only independent predictors of blunted HRR. Conclusions Aerobic capacity and peak exercise D[a-v]O2 are impaired in obese OSA patients, suggesting abnormal peripheral oxygen extraction. EAT thickness is an independent marker of post-exercise HRR, which is a noninvasive marker of autonomic nerve dysfunction accompanying poor cardiovascular prognosis in obese patients.

One year VARC-2-defined clinical outcomes after transcatheter aortic valve implantation with the SAPIEN 3 Abstract Aims To evaluate 1-year outcome after transcatheter aortic valve implantation (TAVI) using the SAPIEN 3 (S3) prosthesis with emphasis on the composite endpoints “clinical efficacy after 30 days” and “time-related valve safety” proposed by the updated Valve Academic Research Consortium (VARC-2). Methods and results Four hundred and two consecutive patients undergoing transfemoral TAVI with the S3 were enrolled. Mean age was 81 ± 6 years, 43% were female and median logistic EuroSCORE I was 12% [8–19]. Device success was achieved in 93% (374/402) with moderate or severe paravalvular leakage (PVL) in 2%. At 1 year all-cause mortality was 8.9% [95% CI 6.4–12.2] and new permanent pacemaker implantation rate was 16% [95% CI 12.7–20.4]. The composite endpoint time-related valve safety occurred in 29% with structural valve deterioration, defined as elevated gradients or more than moderate PVL, occurring in 13%. The clinical efficacy endpoint after 30 days was observed in 37% of patients with the main contributor symptom worsening with New York Heart Association functional class III + in 17% of cases. Conclusions For the first time, VARC-2-defined composite endpoints at 1 year are reported and reveal a considerable proportion of patients experiencing the endpoint of time-related valve safety (29%) and clinical efficacy after 30 days (37%).

Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension Abstract Objective Activation of the sympathetic nervous system increases sodium retention in resistant hypertension. Baroreflex activation therapy (BAT) is an interventional method to reduce sympathetic overactivity in patients with resistant hypertension. This study aimed to assess the effect of BAT on urinary sodium excretion. Methods From 2012 to 2015, consecutive patients with resistant hypertension and blood pressure (BP) above target despite polypharmacy strategies were consecutively included in this observational study. BAT was provided with the individual adaption of programmed parameters over the first months. 24-h urinary sodium excretion (UNa) was estimated at baseline and after 6 months using the Kawasaki formula in patients undergoing BAT. Additionally, the fractional sodium excretion, plasma renin activity, and aldosterone levels were assessed. Results Forty-two patients completed the 6-month follow-up period. Office systolic and ambulatory 24-h systolic BP at baseline were 169 ± 27 mmHg and 148 ± 16 mmHg despite a median intake of 7(3–9) antihypertensive drugs. After 6 months of BAT, systolic office BP decreased to 150 ± 29 mmHg (p < 0.01), 24-h systolic BP to 142 ± 22 mmHg (p = 0.04) and 24-h UNa increased by 37% compared to baseline (128 ± 66 vs. 155 ± 83 mmol/day, p < 0.01). These findings were accompanied by a significant increase in fractional sodium excretion (0.74% [0.43–1.47] to 0.92% [0.61–1.92]; p = 0.02). However, in contrast to the significant BP reduction, eGFR, plasma sodium, renin activity and aldosterone levels did not change during BAT. The increase in sodium excretion was correlated with the change in eGFR (r = 0.371; p = 0.015). Conclusion The present study revealed a significant increase of estimated 24-h UNa which may contribute to the long-term BP-lowering effects of this interventional method.

Thrombus aspiration in patients with ST-elevation myocardial infarction presenting late after symptom onset: long-term clinical outcome of a randomized trial Abstract Background In the largest randomized trial so far, thrombus aspiration failed to reduce the primary endpoint of microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI) presenting late after symptom onset. Long-term clinical outcome data of this trial have not been reported yet. Methods and results A total of 144 patients with STEMI presenting ≥ 12 and ≤ 48 h after symptom onset were randomized to primary percutaneous coronary intervention (PCI) with or without manual thrombus aspiration in a 1:1 fashion. The primary efficacy endpoint was the extent of MVO assessed by cardiac magnetic resonance imaging and showed no significant difference between groups. Long-term clinical follow-up was performed at 4 years. Overall mortality at 4 years reached 18%. There was no significant difference between groups with respect to mortality and major adverse cardiac events defined as the composite of death, myocardial reinfarction and target vessel revascularization. In a multivariate Cox regression model glomerular filtration rate on admission, left ventricular ejection fraction, and cardiogenic shock were independently associated with time-dependent occurrence of death. Conclusion Routine thrombus aspiration in STEMI patients presenting late after symptom onset showed no significant difference with respect to long-term clinical endpoints compared to conventional PCI only.