Cardiomyopathies (ie, diseases of the heart muscle) are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease ...and, over the past 2 decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a “final common pathway” for that specific disorder, but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The “final common pathways” for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy and restrictive cardiomyopathy, the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy, and the desmosome in arrhythmogenic cardiomyopathy. Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and it appears that any of these “final common pathways” can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described. (Circ J 2014; 78: 2347–2356)
The normal function of the human myocardium requires the proper generation and utilization of energy and relies on a series of complex metabolic processes to achieve this normal function. When ...metabolic processes fail to work properly or effectively, heart muscle dysfunction can occur with or without accompanying functional abnormalities of other organ systems, particularly skeletal muscle. These metabolic derangements can result in structural, functional, and infiltrative deficiencies of the heart muscle. Mitochondrial and enzyme defects predominate as disease-related etiologies. In this review, left ventricular noncompaction cardiomyopathy, which is often caused by mutations in sarcomere and cytoskeletal proteins and is also associated with metabolic abnormalities, is discussed. In addition, cardiomyopathies resulting from mitochondrial dysfunction, metabolic abnormalities, storage diseases, and inborn errors of metabolism are described.
Left ventricular non-compaction cardiomyopathy Towbin, Jeffrey A, Dr; Lorts, Angela, MD; Jefferies, John Lynn, MD
The Lancet (British edition),
08/2015, Letnik:
386, Številka:
9995
Journal Article
Recenzirano
Summary Left ventricular non-compaction, the most recently classified form of cardiomyopathy, is characterised by abnormal trabeculations in the left ventricle, most frequently at the apex. It can be ...associated with left ventricular dilation or hypertrophy, systolic or diastolic dysfunction, or both, or various forms of congenital heart disease. Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be induced by exercise or be persistent at rest, but many patients are asymptomatic. Patients on chronic treatment for compensated heart failure sometimes present acutely with decompensated heart failure. Other life-threatening risks of left ventricular non-compaction are ventricular arrhythmias or complete atrioventricular block, presenting clinically as syncope, and sudden death. Genetic inheritance arises in at least 30–50% of patients, and several genes that cause left ventricular non-compaction have been identified. These genes seem generally to encode sarcomeric (contractile apparatus) or cytoskeletal proteins, although, in the case of left ventricular non-compaction with congenital heart disease, disturbance of the NOTCH signalling pathway seems part of a final common pathway for this form of the disease. Disrupted mitochondrial function and metabolic abnormalities have a causal role too. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress in patients with systolic dysfunction. Further, treatment of arrhythmia and implantation of an automatic implantable cardioverter-defibrillator for prevention of sudden death are mainstays of therapy when deemed necessary and appropriate. Patients with left ventricular non-compaction and congenital heart disease often need surgical or catheter-based interventions. Despite progress in diagnosis and treatment in the past 10 years, understanding of the disorder and outcomes need to be improved.
Dilated cardiomyopathy Jefferies, John Lynn, MD; Towbin, Jeffrey A, Prof
The Lancet (British edition),
02/2010, Letnik:
375, Številka:
9716
Journal Article
Recenzirano
Summary Dilated cardiomyopathy is characterised by left ventricular dilation that is associated with systolic dysfunction. Diastolic dysfunction and impaired right ventricular function can develop. ...Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be exercise-induced or persistent at rest. Many patients are asymptomatic. Chronically treated patients sometimes present acutely with decompensated heart failure. Other life-threatening risks are ventricular arrhythmias and atrioventricular block, syncope, and sudden death. Genetic inheritance arises in 30–48% of patients, and inflammatory disorders such as myocarditis or toxic effects from medications, alcohol, or illicit drugs also result in dilated cardiomyopathy. Genes that cause dilated cardiomyopathy generally encode cytoskeletal and sarcomeric (contractile apparatus) proteins, although disturbance of calcium homeostasis also seems to be important. In children, disrupted mitochondrial function and metabolic abnormalities have a causal role. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress. Arrhythmia therapy and prevention of sudden death continue to be mainstays of treatment. Despite progress over the past 10 years, outcomes need to be improved.
Hot Topics in Tetralogy of Fallot Villafañe, Juan, MD; Feinstein, Jeffrey A., MD; Jenkins, Kathy J., MD, MPH ...
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. We explore “hot topics” to highlight areas of emerging science for clinicians and scientists in moving toward a better ...understanding of the long-term management of patients with repaired TOF. From a genetic perspective, the etiology of TOF is multifactorial, with a familial recurrence risk of 3%. Cardiac magnetic resonance is the gold standard assessment tool based on its superior imaging of the right ventricular (RV) outflow tract, pulmonary arteries, aorta, and aortopulmonary collaterals, and on its ability to quantify biventricular size and function, pulmonary regurgitation (PR), and myocardial viability. Atrial re-entrant tachycardia will develop in more than 30% of patients, and high-grade ventricular arrhythmias will be seen in about 10% of patients. The overall incidence of sudden cardiac death is estimated at 0.2%/yr. Risk stratification, even with electrophysiologic testing and cardiac magnetic resonance, remains imperfect. Drug therapy has largely been abandoned, and defibrillator placement, despite its high risks for complications and inappropriate discharges, is often recommended for patients at higher risk. Definitive information about optimal surgical strategies for primary repair to preserve RV function, reduce arrhythmia, and optimize functional status is lacking. Post-operative lesions are often amenable to transcatheter intervention. In selected cases, PR may be treated with transcatheter valve insertion. Ongoing surveillance of RV function is a crucial component of clinical assessment. Except for resynchronization with biventricular pacing, no medical therapies have been shown to be effective after RV dysfunction occurs. In patients with significant PR with RV dilation, optimal timing of pulmonary valve replacement remains uncertain, although accepted criteria are emerging.
Over the last 2 decades, the pathogenic basis for the most common heritable cardiovascular disease, hypertrophic cardiomyopathy (HCM), has been investigated extensively. Affecting approximately 1 in ...500 individuals, HCM is the most common cause of sudden death in young athletes. In recent years, genomic medicine has been moving from the bench to the bedside throughout all medical disciplines including cardiology. Now, genomic medicine has entered clinical practice as it pertains to the evaluation and management of patients with HCM. The continuous research and discoveries of new HCM susceptibility genes, the growing amount of data from genotype-phenotype correlation studies, and the introduction of commercially available genetic tests for HCM make it essential that the modern-day cardiologist understand the diagnostic, prognostic, and therapeutic implications of HCM genetic testing.
Abstract Background Few data exist on prevalence, morbidity, and mortality of pediatric heart failure hospitalizations. We tested the hypotheses that pediatric heart failure–related hospitalizations ...increased over time but that mortality decreased. Factors associated with mortality and length of stay were also assessed. Methods and Results A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed for pediatric (age ≤18 years) heart failure–related hospitalizations for the years 1997, 2000, 2003, and 2006. Hospitalizations did not significantly increase over time, ranging from 11,153 (95% confidence interval CI 8,898–13,409) in 2003 to 13,892 (95% CI 11,528–16,256) in 2006. Hospital length of stay increased from 1997 (mean 13.8 days, 95% CI 12.5–15.2) to 2006 (mean 19.4 days, 95% CI 18.2 to 20.6). Hospital mortality was 7.3% (95% CI 6.9–8.0) and did not vary significantly between years; however, risk-adjusted mortality was less in 2006 (odds ratio 0.70, 95% CI 0.61 to 0.80). The greatest risk of mortality occurred with extracorporeal membrane oxygenation, acute renal failure, and sepsis. Conclusions Heart failure–related hospitalizations occur in 11,000–14,000 children annually in the United States, with an overall mortality of 7%. Many comorbid conditions influenced hospital mortality.
Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular ...noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death.
We retrospectively reviewed all children diagnosed with left ventricular noncompaction at Texas Children's Hospital from January 1990 to January 2009. Patients with congenital cardiac lesions were excluded. Two hundred forty-two children were diagnosed with isolated left ventricular noncompaction over the study period. Thirty-one (12.8%) died, and 13 (5.4%) were received a transplant. One hundred fifty (62%) presented with or developed cardiac dysfunction. The presence of cardiac dysfunction was strongly associated with mortality (hazard ratio, 11; P<0.001). ECG abnormalities were present in 87%, with ventricular hypertrophy and repolarization abnormalities occurring most commonly. Repolarization abnormalities were associated with increased mortality (hazard ratio, 2.1; P=0.02). Eighty children (33.1%) had an arrhythmia, and those with arrhythmias had increased mortality (hazard ratio, 2.8; P=0.002). Forty-two (17.4%) had ventricular tachycardia, with 5 presenting with resuscitated sudden cardiac death. In total, there were 15 cases of sudden cardiac death in the cohort (6.2%). Nearly all patients with sudden death (14 of 15) had abnormal cardiac dimensions or cardiac dysfunction. No patient with normal cardiac dimensions and function without preceding arrhythmias died.
Left ventricular noncompaction has a high mortality rate and is strongly associated with arrhythmias in children. Preceding cardiac dysfunction or ventricular arrhythmias are associated with increased mortality. Children with normal cardiac dimensions and normal function are at low risk for sudden death.
This document provides a pediatric-focused companion to "Defining and Setting National Goals for Cardiovascular Health Promotion and Disease Reduction: The American Heart Association's Strategic ...Impact Goal Through 2020 and Beyond," focused on cardiovascular health promotion and disease reduction in adults and children. The principles detailed in the document reflect the American Heart Association's new dynamic and proactive goal to promote cardiovascular health throughout the life course. The primary focus is on adult cardiovascular health and disease prevention, but critical to achievement of this goal is maintenance of ideal cardiovascular health from birth through childhood to young adulthood and beyond. Emphasis is placed on the fundamental principles and metrics that define cardiovascular health in children for the clinical or research setting, and a balanced and critical appraisal of the strengths and weaknesses of the cardiovascular health construct in children and adolescents is provided. Specifically, this document discusses 2 important factors: the promotion of ideal cardiovascular health in all children and the improvement of cardiovascular health metric scores in children currently classified as having poor or intermediate cardiovascular health. Other topics include the current status of cardiovascular health in US children, opportunities for the refinement of health metrics, improvement of health metric scores, and possibilities for promoting ideal cardiovascular health. Importantly, concerns about the suitability of using single thresholds to identify elevated cardiovascular risk throughout the childhood years and the limits of our current knowledge are noted, and suggestions for future directions and research are provided.
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