Resilience to host inflammation and other perturbations is a fundamental property of gut microbial communities, yet the underlying mechanisms are not well understood. We have found that human gut ...microbes from all dominant phyla are resistant to high levels of inflammation-associated antimicrobial peptides (AMPs) and have identified a mechanism for lipopolysaccharide (LPS) modification in the phylum Bacteroidetes that increases AMP resistance by four orders of magnitude. Bacteroides thetaiotaomicron mutants that fail to remove a single phosphate group from their LPS were displaced from the microbiota during inflammation triggered by pathogen infection. These findings establish a mechanism that determines the stability of prominent members of a healthy microbiota during perturbation.
Atrial fibrillation (AF), the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), is capable of producing symptoms that impact quality of life and is associated with risk for ...embolic stroke. However, the influence of AF on clinical course and outcome in HCM remains incompletely resolved.
Records of 1558 consecutive patients followed at the Tufts Medical Center Hypertrophic Cardiomyopathy Institute for 4.8±3.4 years (from 2004 to 2014) were accessed.
Of the 1558 patients with HCM, 304 (20%) had episodes of AF, of which 226 (74%) were confined to symptomatic paroxysmal AF (average, 5±5; range, 1 to >20), whereas 78 (26%) developed permanent AF, preceded by 7±6 paroxysmal AF episodes. At last evaluation, 277 patients (91%) are alive at 62±13 years of age, including 89% in New York Heart Association class I or II. No difference was found in outcome measures for patients with AF and age- and sex-matched patients with HCM without AF. Four percent of patients with AF died of HCM-related causes (n=11), with annual mortality 0.7%; mortality directly attributable to AF (thromboembolism without prophylactic anticoagulation) was 0.1% per year (n=2 patients). Patients were treated with antiarrhythmic drugs (most commonly amiodarone n=103 or sotalol n=78) and AF catheter ablation (n=49) or the Maze procedure at surgical myectomy (n=72). Freedom from AF recurrence at 1 year was 44% for ablation patients and 75% with the Maze procedure (
<0.001). Embolic events were less common with anticoagulation prophylaxis (4/233, 2%) than without (9/66, 14%) (
<0.001).
Transient symptomatic episodes of AF, often responsible for impaired quality of life, are unpredictable in frequency and timing, but amenable to effective contemporary treatments, and infrequently progress to permanent AF. AF is not a major contributor to heart failure morbidity or a cause of arrhythmic sudden death; when treated, it is associated with low disease-related mortality, no different than for patients without AF. AF is an uncommon primary cause of death in HCM virtually limited to embolic stroke, supporting a low threshold for initiating anticoagulation therapy.
For the first time in 52 years, an American professional football player (Damar Hamlin) collapsed in cardiac arrest during a game, viewed in real-time on national television. The cause of this ...profound event was commotio cordis, that is, blunt non-penetrating chest blow-initiated ventricular fibrillation triggered by physical contact not considered unusual for football. The athlete survived because of timely cardiopulmonary resuscitation and defibrillation provided by first responders organized by the National Football League.
Commotio cordis, albeit rare, was most prominently identified initially in competitive and also recreational sports participants. More recently it became apparent that similar events could occur in almost any circumstance involving a chest blow, such as during everyday activities around the home and with innocent play. The determinant of a commotio cordis event is a blow over the heart in a narrow vulnerable electrical window during dispersion of repolarization. Survival from these events has increased substantially to >60% due to enhanced recognition and prompt resuscitation/defibrillation. In conclusion, in this commentary, we take a timely opportunity to describe in detail the relevant demographics, mechanism/pathophysiology, and clinical course of commotio cordis.
Habitual physical activity reduces coronary heart disease events, but vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in ...susceptible persons. This scientific statement discusses the potential cardiovascular complications of exercise, their pathological substrate, and their incidence and suggests strategies to reduce these complications. Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Hereditary or congenital cardiovascular abnormalities are predominantly responsible for cardiac events among young individuals, whereas atherosclerotic disease is primarily responsible for these events in adults. The absolute rate of exercise-related sudden cardiac death varies with the prevalence of disease in the study population. The incidence of both acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. Maintaining physical fitness through regular physical activity may help to reduce events because a disproportionate number of events occur in least physically active subjects performing unaccustomed physical activity. Other strategies, such as screening patients before participation in exercise, excluding high-risk patients from certain activities, promptly evaluating possible prodromal symptoms, training fitness personnel for emergencies, and encouraging patients to avoid high-risk activities, appear prudent but have not been systematically evaluated.
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.
Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection ...of patients for this therapy is incompletely resolved.
To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM.
Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope.
Appropriate ICD intervention terminating ventricular tachycardia or fibrillation.
The 506 patients were predominately young (mean age, 42 SD, 17 years) at implantation, and most (439 87%) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% SD, 5%), and 3.6% per year for primary prevention (5-year probability, 17% SD, 2%). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%).
In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.
In patients with hypertrophic cardiomyopathy (HC), atrial fibrillation (AF) is common, often poorly tolerated and difficult to treat. Limited data exists regarding safety or efficacy of drug therapy ...for AF rhythm control in HC patients. We performed a retrospective analysis of patients with HC followed >6 months, treated with amiodarone, sotalol, dofetilide, or disopyramide for rhythm control of non-postoperative AF. The duration followed on each medication, reasons for discontinuing, and incidences of adverse events were recorded. Confounding factors including maximum ventricular septal thickness, age, left ventricular ejection fraction, and gender were assessed. Ninety-eight patients had 130 drug treatments (defined as a continuous time on 1 drug); 23 patients were treated with >1 medication. The probability of remaining on a single antiarrhythmic drug at 1 year was 62% and at 3 was 42%. Maximum ventricular septal thickness (hazard ratio 1.05, p = 0.03) and presence of resting outflow gradient (hazard ratio 2.50, p = 0.002) were associated with discontinuation of therapy. Patients treated with amiodarone or sotalol had no serious safety events suggesting that these medications may be reasonably safe. Amiodarone was least likely to be discontinued for inefficacy (8.5%), but likely to be discontinued for side effects (19%). The probability of remaining on sotalol was 74% at 1 year and 50.0% at 3 and it was only discontinued for side effects in 2%. A small number of patients were treated with disopyramide and dofetilide. In conclusion, our data suggest that amiodarone and sotalol are likely safe, and that sotalol may be particularly attractive given its low rate of side effects and low rate of discontinuation.
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