Background Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM), but this can be prevented by an implantable cardioverter-defibrillator (ICD). The aim ...of this study is to evaluate HCM patients with ICDs for primary or secondary prevention of SCD. Methods The study population consisted of all HCM patients with an ICD in 2 tertiary referral clinics. End points during follow-up were total and cardiac mortality, appropriate and inappropriate ICD intervention, and device-related complications. Cox-regression analysis was performed to identify predictors of outcome. Results ICDs were implanted in 134 patients with HCM (mean age 44 ± 17 years, 34% women, 4.2 ± 4.8 years follow-up). Annualized cardiac mortality rate was 3.4% per year and associated with New York Heart Association class III or IV (HR 5.2 2.0-14, P = .002) and cardiac resynchronization therapy (HR 6.3 2.1-20, P = .02). Appropriate ICD interventions occurred in 38 patients (6.8%/year) and was associated with implantation for secondary prevention of SCD (HR 4.0 1.8-9.1, P = .001) and male gender (HR 3.3 1.2-9.0, P = .02). Inappropriate ICD intervention occurred in 21 patients (3.7%/year) and in 20 patients device related complications were documented (3.6%/year). Conclusion ICDs successfully abort life-threatening arrhythmias in HCM patients at increased risk of SCD with an annualized intervention rate of 6.8% per year. End-stage heart failure is the main cause of mortality in these patients. The annualized rate of inappropriate ICD intervention was 3.7% per year, whereas device-related complications occurred 3.6% per year.
Abstract Objectives The aim of this study was to compare outcomes of alcohol septal ablation (ASA) in young and elderly patients with obstructive hypertrophic cardiomyopathy (HCM). Background The ...American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for elderly patients and patients with serious comorbidities. Information on long-term age-specific outcomes after ASA is scarce. Methods This cohort study included 217 HCM patients (age 54 ± 12 years) who underwent ASA because of symptomatic left ventricular outflow tract obstruction. Patients were divided into young (age ≤55 years) and elderly (age >55 years) groups and matched by age in a 1:1 fashion to nonobstructive HCM patients. Results Atrioventricular block following ASA was more common in elderly patients (43% vs. 21%; p = 0.001), resulting in pacemaker implantation in 13% and 5%, respectively (p = 0.06). Residual left ventricular outflow tract gradient, post-procedural New York Heart Association functional class, and necessity for additional septal reduction therapy was comparable between age groups. During a follow-up of 7.6 ± 4.6 years, 54 patients died. The 5- and 10-year survival following ASA was 95% and 90% in patients age ≤55 years and 93% and 82% in patients age >55 years, which was comparable to their control groups. The annual adverse arrhythmic event rate following ASA was 0.7%/year in young patients and 1.4%/year in elderly patients, which was comparable to their control groups. Conclusions ASA is similarly effective for reduction of symptoms in young and elderly patients; however, younger patients have a lower risk of procedure-related atrioventricular conduction disturbances. The long-term mortality rate and risk of adverse arrhythmic events following ASA are low, both in young and elderly patients, and are comparable to age-matched nonobstructive HCM patients.
Heart transplantation (HT) recipients may have tachycardia secondary to cardiac denervation. As higher heart rate predicts worse outcomes in cardiovascular disease, we hypothesized that tachycardia ...and nonuse of β blockers are associated with increased mortality after HT. All patients who underwent HT at our institution from 1987 to 2010 were included. The association of heart rate 3 months after HT and β-blocker use during follow-up to mortality was assessed using Kaplan–Meier and multivariate Cox proportional hazards regression analyses adjusting for clinically relevant baseline variables. From 1987 to 2010, there were 493 HT. After excluding 29 who died within 3 months and 3 with follow-up <3 months, 461 HT recipients (50 ± 2 years; 20% women) were included. Over a follow-up of 12 ± 7 years, selected important univariate predictors of post-HT mortality were older age, male gender, higher body mass index, ischemic cardiomyopathy, longer post-HT intensive care unit stay, and hospitalization and at 3 months, increased mean pulmonary artery pressure, right atrial pressure and pulmonary capillary occlusion pressure, higher heart rate, and nonuse of β blockers during follow-up. In multivariate analysis, older ager, longer hospitalization, higher mean pulmonary artery pressure, higher heart rate at 3 months (hazard ratio 1.02 per beat, 95% confidence interval 1.008 to 1.035, p = 0.02) and nonuse of β blockers (hazard ratio 1.43, 95% confidence interval 1.002 to 2.031, p <0.05) were associated with mortality. In conclusion, in a large single-center cohort of HT recipients, higher heart rate and nonuse of β blockers were independently associated with higher mortality.
Abstract Objectives The aim of this study was to determine the long-term outcomes (all-cause mortality and sudden cardiac death SCD) after medical therapy, alcohol septal ablation (ASA), and myectomy ...in patients with hypertrophic cardiomyopathy (HCM). Background Therapy-resistant obstructive HCM can be treated both surgically and percutaneously. But there is no consensus on the long-term effects of ASA, especially on SCD. Methods This study included 1,047 consecutive patients with HCM (mean age 52 ± 16 years, 61% men) from 3 tertiary referral centers. A total of 690 patients (66%) had left ventricular outflow tract gradients ≥ 30 mm Hg, of whom 124 (12%) were treated medically, 316 (30%) underwent ASA, and 250 (24%) underwent myectomy. Primary endpoints were all-cause mortality and SCD. Kaplan-Meier graphs and Cox regression models were used for statistical analyses. Results The mean follow-up period was 7.6 ± 5.3 years. Ten-year survival was similar in medically treated patients (84%), ASA patients (82%), myectomy patients (85%), and patients with nonobstructive HCM (85%) (log-rank p = 0.50). The annual rate of SCD was low after invasive therapy: 1.0%/year in the ASA group and 0.8%/year in the myectomy group. Multivariate analysis demonstrated that the risk for SCD was lower after myectomy compared with the ASA group (hazard ratio: 2.1; 95% confidence interval: 1.0 to 4.4; p = 0.04) and the medical group (hazard ratio: 2.3; 95% confidence interval: 1.0 to 5.2; p = 0.04). Conclusions Patients with obstructive HCM who are treated at referral centers for HCM care have good survival and low SCD risk, similar to that of patients with nonobstructive HCM. The SCD risk of patients after myectomy was lower than after ASA or in the medical group.
Objectives Maintenance of endothelial homeostasis may prevent the development of cardiac allograft vasculopathy (CAV). This study investigated whether biomarkers related to endothelial injury and ...endothelial repair discriminate between CAV-negative and CAV-positive heart transplant recipients. Background CAV is the most important determinant of cardiac allograft survival and a major cause of death after heart transplantation. Methods Fifty-two patients undergoing coronary angiography between 5 and 15 years after heart transplantation were recruited in this study. Flow cytometry was applied to quantify endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles. Cell culture was used for quantification of circulating EPC number and hematopoietic progenitor cell number and for analysis of EPC function. Results The EPC number and function did not differ between CAV-negative and CAV-positive patients. In univariable models, age, creatinine, steroid dose, granulocyte colony–forming units, apoptotic CECs, and apoptotic endothelial microparticles discriminated between CAV-positive and CAV-negative patients. The logistic regression model containing apoptotic CECs and apoptotic endothelial microparticles as independent predictors provided high discrimination between CAV-positive and CAV-negative patients (C-statistic 0.812; 95% confidence interval: 0.692 to 0.932). In a logistic regression model with age and creatinine as covariates, apoptotic CECs (p = 0.0112) and apoptotic endothelial microparticles (p = 0.0141) were independent predictors (C-statistic 0.855; 95% confidence interval: 0.756 to 0.953). These 2 biomarkers remained independent predictors when steroid dose was introduced in the model. Conclusions The high discriminative ability of apoptotic CECs and apoptotic endothelial microparticles is a solid foundation for the development of clinical prediction models of CAV.
Bleeding complications are frequent adverse events in patients supported with axial continuous-flow pumps. Previous retrospective studies demonstrated that bleeding events in patients with the ...HeartMate II (Thoratec Corp, Pleasanton, CA) were attributed to acquired von Willebrand syndrome. We sought to analyze the von Willebrand factor (VWF) profile in patients receiving a HeartMate II or a CircuLite (Saddle Brook, NJ,) device (Synergy Pocket Micro-pump) prospectively.
Prospectively analyzed were 34 patients supported with left ventricular assist device (LVAD; 26 with HeartMate II and 8 with CircuLite). The control group comprised 20 patients who underwent heart transplantation (HTx). Blood samples were taken pre-operatively and at 14 days and 3, 6, 9, and 12 months post-operatively.
Patients with LVADs had a high incidence of bleeding complications. From the immediate post-operative phase throughout the entire observation, the VWF ristocetin cofactor activity (Rco)/antigen (Ag) ratio of patients with HeartMate II and CircuLite devices was consistently lower compared with HTx patients. No correlation was found between the individual VWF:Rco/Ag ratio and bleeding events or transfusion requirements. The VWF:Rco/Ag ratio normalized immediately in patients who received HTx.
Acquired von Willebrand syndrome was confirmed to occur immediately after the implantation of both types of LVAD and persisted up to 12 months. A lower VWF:Rco/Ag ratio was associated with larger transfusion requirements. Acquired von Willebrand syndrome resolves after LVAD explantation.
Cardiac allograft vasculopathy (CAV) is a limiting factor for the long-term survival of heart transplant recipients. Clinical decisions and care may be improved by the development of prediction ...models based on circulating biomarkers. The endothelium may play a central pathogenetic role in the development of CAV. We evaluated the hypothesis that endothelium-enriched microRNAs (miRNAs) discriminate between patients with and without CAV.
This cross-sectional study recruited 52 patients undergoing coronary angiography between 5 and 15 years after heart transplantation. Circulating levels of endothelium-enriched miRNAs (miR-21-5p, miR-92a-3p, miR-92a-1-5p, miR-126-3p, and miR-126-5p) were quantified by real-time reverse transcription polymerase chain reaction. The discriminative ability of logistic regression models was evaluated using the concordance (C) statistic.
Median plasma levels of miR-210-5p, miR-92a-3p, miR-126-3p, and miR-126-5p were 1.82-fold (p = not significant), 1.87-fold (p < 0.05), 1.94-fold (p = 0.074), and 1.59-fold (p = 0.060) higher in patients with CAV than in patients without CAV. Recipient age (C statistic = 0.689; 95% confidence interval CI, 0.537-0.842), and levels of serum creatinine (C statistic = 0.703; 95% CI, 0.552-0.854), miR-92a-3p (C statistic = 0.682; 95% CI, 0.533-0.831), and miR-126-5p (C statistic = 0.655; 95% CI, 0.502-0.807) predicted CAV status in univariable models. In multivariable logistic regression models with recipient age and creatinine as covariates, miR-126-5p (chi-square = 4.37(1), p = 0.037), miR-92a-3p (chi-square = 6.01(1), p = 0.014), and the combination of miR-126-5p and miR-92a-3p (chi-square = 8.16(2), p = 0.017) added significant information. The model with age, creatinine, miR-126-5p, and miR-92a-3p as covariables conferred good discrimination between patients without and with CAV (C statistic = 0.800; 95% CI, 0.674-0.926).
Endothelium-enriched miRNAs have diagnostic ability for CAV beyond clinical predictors.
This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.
In 298 patients, we measured 7.6 years ...post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.
In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg;
< 0.0001) and with HF2 (+0.42 and +0.62 mm Hg;
≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg;
< 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (
≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65;
= 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (
≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%;
= 0.023) and net reclassification (+30.3%;
= 0.010) improvement.
Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered.
Percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (LMCA) is controversial. In 143 patients who underwent PCI of the unprotected LMCA, 30-day mortality was compared ...with predicted cumulative risk-adjusted perioperative surgical mortality based on logistic European System for Cardiac Operative Risk Evaluation. One-year clinical follow-up was completed in all patients. The overall major adverse cardiac event rate at 1 year was 34.3%, reflecting the high-risk profile of the patient population. Twelve patients (8%) experienced an acute myocardial infarction and 16 (11%) underwent target lesion revascularization. In 31 patients (22%) who died during the first year, median logistic European System for Cardiac Operative Risk Evaluation was 30%. Calculated RRs showed significantly lower 30-day mortality using PCI compared with predicted surgical mortality (RR 0.54, 95% confidence interval 0.31 to 0.86). Angiographic follow-up in 90 of the 118 patients alive at 6 months showed binary restenosis of 6% in patients treated with drug-eluting stents versus 29% in patients receiving bare-metal stents (p ≤0.01). In conclusion, PCI for unprotected LMCA disease was associated with acceptable short- and medium-term outcomes in patients at low to intermediate risk of bypass surgery. Mortality remains high in very high-risk patients unsuitable for surgery. However, in selected indications, PCI of the LMCA can offer an alternative to surgery, especially when using drug-eluting stents.
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