Ross Garberich

Prevention of Sudden Cardiac Death With Implantable Cardioverter-Defibrillators in Children and Adolescents With Hypertrophic Cardiomyopathy

OBJECTIVES The aim of this study was to determine the efficacy of implantable cardioverter-defibrillators (ICDs) in children and adolescents with hypertrophic cardiomyopathy (HCM). BACKGROUND HCM is the most common cause of sudden death in the young. The availability of ICDs over the past decade for HCM has demonstrated the potential for sudden death prevention, predominantly in adult patients. METHODS A multicenter international registry of ICDs implanted (1987 to 2011) in 224 unrelated children and adolescents with HCM judged at high risk for sudden death was assembled. Patients received ICDs for primary (n = 188) or secondary (n = 36) prevention after undergoing evaluation at 22 referral and nonreferral institutions in the United States, Canada, Europe, and Australia. RESULTS Defibrillators were activated appropriately to terminate ventricular tachycardia or ventricular fibrillation in 43 of 224 patients (19%) over a mean of 4.3 ± 3.3 years. ICD intervention rates were 4.5% per year overall, 14.0% per year for secondary prevention after cardiac arrest, and 3.1% per year for primary prevention on the basis of risk factors (5-year cumulative probability 17%). The mean time from implantation to first appropriate discharge was 2.9 ± 2.7 years (range to 8.6 years). The primary prevention discharge rate terminating ventricular tachycardia or ventricular fibrillation was the same in patients who underwent implantation for 1, 2, or ≥3 risk factors (12 of 88 [14%], 10 of 71 [14%], and 4 of 29 [14%], respectively, p = 1.00). Extreme left ventricular hypertrophy was the most common risk factor present (alone or in combination with other markers) in patients experiencing primary prevention interventions (17 of 26 [65%]). ICD-related complications, particularly inappropriate shocks and lead malfunction, occurred in 91 patients (41%) at 17 ± 5 years of age. CONCLUSIONS In a high-risk pediatric HCM cohort, ICD interventions terminating life-threatening ventricular tachyarrhythmias were frequent. Extreme left ventricular hypertrophy was most frequently associated with appropriate interventions. The rate of device complications adds a measure of complexity to ICD decisions in this age group.

Causes of Delay and Associated Mortality in Patients Transferred With ST-Segment–Elevation Myocardial Infarction

Background— Regional ST-segment–elevation myocardial infarction systems are being developed to improve timely access to primary percutaneous coronary intervention (PCI). System delays may diminish the mortality benefit achieved with primary PCI in ST-segment–elevation myocardial infarction patients, but the specific reasons for and clinical impact of delays in patients transferred for PCI are unknown. Methods and Results— This was a prospective, observational study of 2034 patients transferred for primary PCI at a single center as part of a regional ST-segment–elevation myocardial infarction system from March 2003 to December 2009. Despite long-distance transfers, 30.4% of patients (n=613) were treated in ⩽90 minutes and 65.7% (n=1324) were treated in ⩽120 minutes. Delays occurred most frequently at the referral hospital (64.0%, n=1298), followed by the PCI center (15.7%, n=317) and transport (12.6%, n=255). For the referral hospital, the most common reasons for delay were awaiting transport (26.4%, n=535) and emergency department delays (14.3%, n=289). Diagnostic dilemmas (median, 95.5 minutes; 25th and 75th percentiles, 72–127 minutes) and nondiagnostic initial ECGs (81 minutes; 64–110.5 minutes) led to delays of the greatest magnitude. Delays caused by cardiac arrest and/or cardiogenic shock had the highest in-hospital mortality (30.6%), in contrast with nondiagnostic initial ECGs, which, despite long treatment delays, did not affect mortality (0%). Significant variation in both the magnitude and clinical impact of delays also occurred during the transport and PCI center segments. Conclusions— Treatment delays occur even in efficient systems for ST-segment–elevation myocardial infarction care. The clinical impact of specific delays in interhospital transfer for PCI varies according to the cause of the delay.

Risk Stratification and Outcome of Patients With Hypertrophic Cardiomyopathy ≥60 Years of Age

Background— Hypertrophic cardiomyopathy (HCM) is prominently associated with risk for sudden death and disease progression, largely in young patients. Whether patients of more advanced age harbor similar risks is unresolved, often creating clinical dilemmas, particularly in decisions for primary prevention of sudden death with implantable defibrillators. Methods and Results— We studied 428 consecutive HCM patients presenting at ≥60 years of age and followed for 5.8±4.8 years; 53% were women. Of the 428 patients, 279 (65%) survived to 73±7 years of age (range, 61–96 years), most (n=245, 88%) with no/mild symptoms, including 135 with ≥1 conventional sudden death risk factors and 50 (37%) with late gadolinium enhancement. Over follow-up, 149 (35%) died at 80±8 years of age, mostly from non–HCM-related causes (n=133, 31%), including a substantial proportion from noncardiac disease (n=54). Sixteen patients (3.7%) had HCM-related mortality events (0.64%/y), including embolic stroke (n=6), progressive heart failure or transplantation (n=3), postoperative complications (n=2), and arrhythmic sudden death events (n=5, 1.2% [0.20%/y]). All-cause mortality was increased in HCM patients ≥60 years of age compared with an age-matched US general population, predominantly as a result of non–HCM-related diseases (P<0.001; standard mortality ratio, 1.5). Conclusions— HCM patients surviving into the seventh decade of life are at low risk for disease-related morbidity/mortality, including sudden death, even with conventional risk factors. These data do not support aggressive prophylactic defibrillator implantation at advanced ages in HCM. Other cardiac or noncardiac comorbidities have a greater impact on survival than HCM in older patients.

Hypertrophic Cardiomyopathy in Adulthood Associated With Low Cardiovascular Mortality With Contemporary Management Strategies

BACKGROUND Hypertrophic cardiomyopathy (HCM) has been prominently associated with adverse disease complications, including sudden death or heart failure death and a generally adverse prognosis, with annual mortality rates of up to 6%. OBJECTIVES This study determined whether recent advances in management strategy, including implantable cardioverter-defibrillators (ICDs), heart transplantation, or other therapeutic measures have significantly improved survival and the clinical course of adult HCM patients. METHODS We addressed long-term outcomes in 1,000 consecutive adult HCM patients presenting at 30 to 59 years of age (mean 45±8 years) over 7.2±5.2 years of follow-up. RESULTS Of 1,000 patients, 918 (92%) survived to 53±9.2 years of age (range 32 to 80 years) with 91% experiencing no or only mild symptoms at last evaluation. HCM-related death occurred in 40 patients (4% [0.53%/year]) at 50±10 years from the following events: progressive heart failure (n=17); arrhythmic sudden death (SD) (n=17); and embolic stroke (n=2). In contrast, 56 other high-risk patients (5.6%) survived life-threatening events, most commonly with ICD interventions for ventricular tachyarrhythmias (n=33) or heart transplantation for advanced heart failure (n=18 [0.79%/year]). SD occurred in patients who declined ICD recommendations, had evaluations before application of prophylactic ICDs to HCM, or were without conventional risk factors. The 5- and 10-year survival rates (confined to HCM deaths) were 98% and 94%, respectively, not different from the expected all-cause mortality in the general U.S. population (p=0.25). Multivariate independent predictors of adverse outcome were younger age at diagnosis, female sex, and increased left atrial dimension. CONCLUSIONS In a large longitudinally assessed adult HCM cohort, we have demonstrated that contemporary management strategies and treatment interventions, including ICDs for SD prevention, have significantly altered the clinical course, now resulting in a low disease-related mortality rate of 0.5%/year and an opportunity for extended longevity.

Long-term survival in patients with refractory angina

AIMS An increasing number of patients with severe coronary artery disease (CAD) are not candidates for traditional revascularization and experience angina in spite of excellent medical therapy. Despite limited data regarding the natural history and predictors of adverse outcome, these patients have been considered at high risk for early mortality. METHODS AND RESULTS The OPtions In Myocardial Ischemic Syndrome Therapy (OPTIMIST) program at the Minneapolis Heart Institute offers traditional and investigational therapies for patients with refractory angina. A prospective clinical database includes detailed baseline and yearly follow-up information. Death status and cause were determined using the Social Security Death Index, clinical data, and death certificates. Time to death was analysed using survival analysis methods. For 1200 patients, the mean age was 63.5 years (77.5% male) with 72.4% having prior coronary artery bypass grafting, 74.4% prior percutaneous coronary intervention, 72.6% prior myocardial infarction, 78.3% 3-vessel CAD, 23.0% moderate-to-severe left-ventricular (LV) dysfunction, and 32.6% congestive heart failure (CHF). Overall, 241 patients died (20.1%: 71.8% cardiovascular) during a median follow-up 5.1 years (range 0-16, 14.7% over 9). By Kaplan-Meier analysis, mortality was 3.9% (95% CI 2.8-5.0) at 1 year and 28.4% (95% CI 24.9-32.0) at 9 years. Multivariate predictors of all-cause mortality were baseline age, diabetes, angina class, chronic kidney disease, LV dysfunction, and CHF. CONCLUSION Long-term mortality in patients with refractory angina is lower than previously reported. Therapeutic options for this distinct and growing group of patients should focus on angina relief and improved quality of life.

Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction.

BACKGROUND Initial clinical trials from Europe have demonstrated that the administration of bone marrow-derived mononuclear cells (BMCs) may improve left ventricular (LV) function in patients following ST-elevation myocardial infarction (STEMI). However, results from trials performed in the United States have not yet been presented. METHODS We developed a phase 1, randomized, placebo-controlled, double-blind trial to investigate the effects of BMC administration in patients following STEMI on recovery of LV function using cardiac magnetic resonance imaging (cMRI). Forty patients with moderate to large anterior STEMIs were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days following successful primary angioplasty and stenting (percutaneous coronary intervention) of the left anterior descending coronary artery. RESULTS Administration of BMC was safely performed in a high-risk cohort with minimal major adverse clinical event rates, and all patients remain alive to date. Left ventricular ejection fraction increased from 49.0% +/- 9.5% at baseline to 55.2% +/- 9.8% at 6 months by cMRI in the BMC group (P < .05), which was not different from the increase in the placebo group (48.6% +/- 8.5% to 57.0% +/- 13.4%, P < .05). Left ventricular end-diastolic volume decreased by 4 mL/m(2) in the BMC group at 6 months but increased significantly in the placebo group (17 mL/m(2), P < .01). CONCLUSIONS This phase 1 study from the United States confirms the ongoing safety profile of BMC administration in patients following STEMI. The improvement in LV ejection fraction at 6 months by cMRI in the cell therapy group was not different than the placebo group. However, BMC administration had a favorable effect on LV remodeling at 6 months.

Epidemiology of Sudden Death in Young, Competitive Athletes Due to Blunt Trauma

BACKGROUND: Sudden deaths of young competitive athletes are highly visible events that have a substantial effect on families and communities. Recent attention has focused predominantly on cardiovascular causes, and less on traumatic organ damage. OBJECTIVE: To define the clinical profile, epidemiology, and frequency of trauma-related deaths in young US athletes. METHODS: We analyzed the 30-year US National Registry of Sudden Death in Young Athletes (1980–2009) by using systematic identification and tracking strategies. RESULTS: Of 1827 deaths of athletes aged 21 years or younger, 261 (14%) were caused by trauma-related injuries, usually involving the head and/or neck (mean: 16 ± 2 years; 90% male) in 22 sports. The highest number of events in a single year was 16 (1986), with an average of 9 per year throughout 30 years. The mortality rate was 0.11 in 100 000 participations (95% confidence interval: 0.08–0.15). The largest number of deaths was in football (148 [57%]), including 17 high school athletes who sustained concussions shortly before fatal head trauma (“second-impact syndrome”). Football deaths were more frequent in defensive players, although the single most common position involved was running back (61% of offensive players). CONCLUSIONS: In a large community-based national registry, sudden deaths caused by blunt trauma in young athletes aged 21 years or younger were relatively uncommon with 16 or fewer per year, about fourfold less than cardiovascular deaths. These fatalities were most frequent in football, and an important proportion of deaths after head blows in high school football were associated with a recent history of symptomatic concussion.

Assessment of an iterative reconstruction algorithm (SAFIRE) on image quality in pediatric cardiac CT datasets

BACKGROUND Pediatric cardiac patients often undergo repeat diagnostic testing, resulting in relatively high cumulative medical radiation exposure. Low-dose CT scanning techniques used to decrease radiation exposure may result in reduced image quality. OBJECTIVE This study evaluates a prototype iterative reconstruction algorithm, sinogram-affirmed iterative reconstruction (SAFIRE), to determine the effect on qualitative and quantitative measures of image quality in pediatric cardiac CT datasets, compared with a standard weighted filtered back projection (wFBP) algorithm. METHODS Seventy-four datasets obtained on a 128-slice dual-source CT system were evaluated for image quality using both the wFBP and the prototype iterative reconstruction algorithm. Contrast, noise, contrast-to-noise ratio, signal-to-noise ratio, and qualitative image quality were compared between groups. Data were analyzed as medians and 25th and 75th percentiles, and groups were compared with the use of the Wilcoxon singed-rank test or k sample equality of medians test. RESULTS There was a 34% decrease in noise, a 41% increase in contrast-to-noise ratio, and a 56% increase in signal-to-noise ratio in the prototype iterative reconstruction, compared with wFBP. All differences were statistically significant (P < 0.001). Qualitative measures of image noise and noise texture were also improved in the iterative reconstruction group (P < 0.001 for both). Diagnostic confidence was similar between reconstruction techniques. Median scan dose length product was 15.5 mGy · cm. CONCLUSION The prototype iterative reconstruction algorithm studied significantly reduces image noise and improves qualitative and quantitative measures of image quality in low-dose pediatric CT datasets, compared with standard wFBP.

Safety and efficacy of a pharmaco-invasive reperfusion strategy in rural ST-elevation myocardial infarction patients with expected delays due to long-distance transfers

AIMS To determine the safety and efficacy of a pharmaco-invasive reperfusion strategy utilizing half-dose fibrinolysis combined with transfer for immediate percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients presenting to remote rural hospitals. Primary PCI is preferred for STEMI if performed in a timely manner. However, <20% of STEMI patients transferred for PCI in the USA have door-to-balloon times <2 h. METHODS AND RESULTS Prospective data from the Level 1 MI programme were analysed. All STEMI patients presenting to the Minneapolis Heart Institute or 31 referral hospitals received aspirin, clopidogrel, and unfractionated heparin (UFH) at the presenting hospital and those presenting to hospitals ≥60 miles away also received half-dose fibrinolytic with transfer for immediate PCI. From April 2003 through December 2009, we enrolled 2634 consecutive STEMI patients in the Level 1 MI database including 660 transferred from remote hospitals utilizing pharmaco-invasive therapy and 600 patients who presented directly to the PCI centre. There were no significant differences in 30-day mortality (5.5 vs. 5.6%; P= 0.94), stroke (1.1 vs. 1.3%; P= 0.66) or major bleeding (1.5 vs. 1.8%; P= 0.65), or re-infarction/ischaemia (1.2 vs. 2.5%; P= 0.088) in patients receiving a pharmaco-invasive strategy compared with patients presenting directly to the PCI centre, despite a significantly longer door-to-balloon time. CONCLUSION Within a regional STEMI system of care, half-dose fibrinolysis combined with immediate transfer for PCI may be a safe and effective option for STEMI patients with expected delays due to long-distance transfer.

Contemporary Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy

BACKGROUND Left ventricular outflow tract gradients are absent in an important proportion of patients with hypertrophic cardiomyopathy (HCM). However, the natural course of this important patient subgroup remains largely unresolved. OBJECTIVES The authors systematically employed exercise (stress) echocardiography to define those patients without obstruction to left ventricular outflow at rest and/or under physiological exercise and to examine their natural history and clinical course to create a more robust understanding of this complex disease. METHODS We prospectively studied 573 consecutive HCM patients in 3 centers (44 ± 17 years; 66% male) with New York Heart Association functional class I/II symptoms at study entry, including 249 in whom left ventricular outflow tract obstruction was absent both at rest and following physiological exercise (<30 mm Hg; nonobstructive HCM) and retrospectively assembled clinical follow-up data. RESULTS Over a median follow-up of 6.5 years, 225 of 249 nonobstructive patients (90%) remained in classes I/II, whereas 24 (10%) developed progressive heart failure to New York Heart Association functional classes III/IV. Nonobstructive HCM patients were less likely to experience advanced limiting class III/IV symptoms than the 324 patients with outflow obstruction (1.6%/year vs. 7.4%/year rest obstruction vs. 3.2%/year provocable obstruction; p < 0.001). However, 7 nonobstructive patients (2.8%) did require heart transplantation for progression to end stage versus none of the obstructive patients. HCM-related mortality among nonobstructive patients was low (n = 8; 0.5%/year), with 5- and 10-year survival rates of 99% and 97%, respectively, which is not different from expected all-cause mortality in an age- and sex-matched U.S. population (p = 0.15). CONCLUSIONS HCM patients with nonobstructive disease appear to experience a relatively benign clinical course, associated with a low risk for advanced heart failure symptoms, other disease complications, and HCM-related mortality, and largely without the requirement for major treatment interventions. A small minority of nonobstructive HCM patients progress to heart transplant.