Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sudden cardiac death (SCD) accounts for more than half of all cardiac deaths occurring each year in the United States. Although it has several causes, patients at greatest risk are those with coronary artery disease and impaired left ventricular function, heart failure secondary to ischemia or idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, documented sustained ventricular tachycardia or ventricular fibrillation, and survivors of cardiac arrest. The presence of asymptomatic ventricular arrhythmias, positive signal-averaged electrocardiogram (ECG), low heart rate variability index, or inducible ventricular tachycardia or ventricular fibrillation increases the risk. In primary prevention trials in patients with ischemic heart disease, beta-blockers reduced both total mortality and SCD, whereas class I antiarrhythmic drugs, especially class IC, increased mortality. Among class III agents, d,l-sotalol and dofetilide have a neutral effect on mortality, whereas d-sotalol increases mortality. Amiodarone has a neutral effect on total and cardiac mortality but does reduce the risk of arrhythmic death and cardiac arrest. Three primary prevention trials in patients with ischemic heart disease were conducted with implantable cardioverter-defibrillators (ICDs). Patients with low ejection fractions (EFs), asymptomatic ventricular arrhythmias, and inducible ventricular tachycardia or ventricular fibrillation had significant reductions in total, cardiac, and arrhythmic death with ICDs compared with either no drug therapy or conventional antiarrhythmic agents. The ICDs did not reduce mortality in patients with low EFs and a positive signal-averaged ECG undergoing coronary bypass graft. In those with heart failure, beta-blockers reduced total and SCD mortality, but dofetilide and amiodarone had a neutral effect on mortality. In the secondary prevention of SCD, antiarrhythmic drugs alone generally are not thought to improve survival. In three trials in patients with documented sustained ventricular tachycardia or ventricular fibrillation, or survivors of SCD, ICDs reduced cardiac and arrhythmic mortality. Total mortality, however, was significantly reduced in only one of these trials. The role of antiarrhythmic drugs in secondary prevention of SCD is limited to patients in whom ICD is inappropriate or in combination with ICD. Antiarrhythmics can be given selectively with ICDs to decrease episodes of ventricular tachycardia or fibrillation to reduce ICD discharges, to suppress episodes of nonsustained ventricular tachycardia that trigger ICD discharges, to slow the rate of ventricular tachycardia to increase hemodynamic stability, to allow effective antitachycardia pacing, or to suppress supraventricular arrhythmias.
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PMID:Role of antiarrhythmic therapy in patients at risk for sudden cardiac death: an evidence-based review. 1134 45

Hypertrophic cardiomyopathy (HC) is associated with an increased risk of sudden cardiac death or death from heart failure. Little is known of the pathologic substrate for risk of premature death in this disease. We therefore set out to correlate the pathologic findings with the mode of death and risk profile in 75 patients with HC. Hearts with HC were obtained after death or transplantation. The clinical details were correlated with the macroscopic findings and the percent fibrosis, disarray, and small-vessel disease across 19 sections of each heart. Thirty-nine patients died suddenly, 28 had end-stage heart failure, and 8 died of other causes. Myocyte disarray correlated positively with evidence of ischemia (r = 0.5, p <0.0001), and was greater in patients who died before age 21 years (mean disarray 33% vs 18%, p <0.0001) and in those with an abnormal vascular response to exercise (mean disarray and 30% vs 19%, p = 0.04). Myocardial fibrosis was greater in patients who died in heart failure (mean percent fibrosis was 2.8% versus 0.9%, p = 0.003), and in patients with nonsustained ventricular tachycardia or a high risk fractionation study (4.9% vs 2.7%, p = 0.04, and 6.84% vs 2.8%, p = 0.03, respectively). In conclusion, young patients who die with HC have greater disarray than their older counterparts. In contrast, myocardial fibrosis is the substrate for premature deaths from heart failure and is associated with an increased risk of a primary ventricular arrhythmia.
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PMID:Relation between myocyte disarray and outcome in hypertrophic cardiomyopathy. 1147 7

Sudden unexpected death, often occurring in young, asymptomatic patients, is the most devastating facet of the natural history of hypertrophic cardiomyopathy, and appears to be the consequence of primary ventricular tachyarrhythmias arising in an electrically unstable myocardial substrate characterized by disorganized cellular architecture, ischemia, cell death, and replacement scarring. Although precise identification of all hypertrophic cardiomyopathy patients at high risk for a catastrophic event is a clinical challenge, effective treatment strategies for the prevention of sudden death with the implantable cardioverter-defibrillator are now available.
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PMID:Risk stratification and prevention of sudden death in hypertrophic cardiomyopathy. 1204 95

Cardiomyopathies are diseases of heart muscle that may result from a diverse array of conditions that damage the heart and other organs and impair myocardial function, including infection, ischemia, and toxins. However, they may also occur as primary diseases restricted to striated muscle. Over the past decade, the importance of inherited gene defects in the pathogenesis of primary cardiomyopathies has been recognized, with mutations in some 18 genes having been identified as causing hypertrophic cardiomyopathy (HCM) and/or dilated cardiomyopathy (DCM). Defining the role of these genes in cardiac function and the mechanisms by which mutations in these genes lead to hypertrophy, dilation, and contractile failure are major goals of ongoing research. Pathophysiological mechanisms that have been implicated in HCM and DCM include the following: defective force generation, due to mutations in sarcomeric protein genes; defective force transmission, due to mutations in cytoskeletal protein genes; myocardial energy deficits, due to mutations in ATP regulatory protein genes; and abnormal Ca2+ homeostasis, due to altered availability of Ca2+ and altered myofibrillar Ca2+ sensitivity. Improved understanding that will result from these studies should ultimately lead to new approaches for the diagnosis, prognostic stratification, and treatment of patients with heart failure.
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PMID:Molecular mechanisms of inherited cardiomyopathies. 1227 Sep 49

Activation of cardiac myofilaments is a complex process involving steric, allosteric, and cooperative mechanisms. The complexity of the protein-protein interactions that result in the rise and fall of tension in the heartbeat provide many points that may be modified by various control mechanisms. These include modulation by the sarcomere length, covalent modulation by protein phosphorylation and non-covalent modulation by the chemical environment surrounding the myofilaments. We focus here on effects of pH change in the context of one of the mutations in cardiac troponin T (R92Q) that causes familial hypertrophic cardiomyopathy (FHC). We tested whether this change in charge would manifest itself functionally by a difference in the pCa-force relations of skinned fiber bundles activated at pH values of 6.5, 7.0 and 7.5. Fiber bundles containing the cTnT-R92Q mutant demonstrated an increase in sensitivity to Ca2+ at all three pH values. However, the relative magnitude of the increase in Ca2+-sensitivity induced by the mutant cTnT increased as the pH was decreased from pH 7.5 to pH 7.0 and to pH 6.5. Maximum force generated by the myofilaments fell as pH was lowered over this range, but the percent fall in maximum force was the same for fiber bundles containing wild-type and mutant cTnT. Our results indicate that ischemia that may be associated with FHC may exacerbate the functional changes induced by the cTnT mutation.
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PMID:Molecular mechanisms of cardiac myofilament activation: modulation by pH and a troponin T mutant R92Q. 1247 43

There are some human diseases associated with mitochondrial DNA genome defect. Now many studies think that: oxygen radical resulting from oxidative phosphorylation(OXPHOS) disorder caused by myocardium ischemia and the increased OXPHOS induction damage mitochondrial DNA. Chronic damage accumulations lead to mitochondrial DNA deletion or point mutation in the end which show mitochondrial DNA 5.0 kb or 7.4 kb deletion and point mutation at position C15452A in the cytochrome b gene; the conservative sequence mutation of tRNA gene such as A4300G, C4320T point mutation in the tRNA Ilegene, A3243G point mutation in the tRNA leu gene etc result in defective contractile proteins whose persistent and inefficient contraction may increase the myocardium's metabolic demands for ATP and leads to cardiac hypertrophy. In this article, we review the study on the association of mitochondrial DNA mutation with ischemic cardiomyopathy and hypertrophic cardiomyopathy.
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PMID:[The research progress of the association of mitochondrial DNA mutation with cardiomyopathy]. 1253 76

Thanks to advances in molecular biology during the last decade, the etiology of hypertrophic cardiomyopathy has been elucidated. Although more than 150 causal mutations of 9 genes that encode contractile proteins have been identified, many of the pathogenetic mechanisms remain unclear. In this review we discuss the current state of knowledge of the functional effects of some mutations, particularly two of the most lethal beta-myosin mutations -Arg403Gln and Arg723Gly (Barcelona mutation)- and their contributions to the pathogenesis of hypertrophy, sudden death and ischemia. Their potential roles in diagnostic and therapeutic strategies are emphasized.
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PMID:[Hypertrophic cardiomyopathy. Genetic basis and clinical implications]. 1551 86

Symptoms and signs of myocardial ischemia are often found in patients with hypertrophic cardiomyopathy (HCM) despite angiographically normal coronary arteries. Myocardial ischemia is deemed responsible for some of the lethal complications of HCM including ventricular arrhythmias, sudden death, progressive left ventricular remodeling, and systolic dysfunction. In the past decade, a number of studies using positron emission tomography have demonstrated severe impairment of the vasodilator response to dipyridamole in the majority of HCM patients, not only in the hypertrophied septum but also in the non-hypertrophied left ventricular free wall. In the absence of coronary stenoses, this finding is indicative of diffuse microvascular dysfunction, in line with the autoptic evidence of widespread abnormalities of the intramural coronary arterioles. In turn, microvascular dysfunction represents a very likely substrate for recurrent ischemia. This may account for the fact that microvascular dysfunction has recently been shown to represent an early and powerful predictor of an unfavorable outcome in HCM. The aim of this article is to provide a concise overview of the available evidence of microvascular dysfunction and ischemia in HCM, and to speculate on the potential implications for management.
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PMID:Coronary microvascular dysfunction and ischemia in hypertrophic cardiomyopathy. Mechanisms and clinical consequences. 1555 27

Left ventricular hypertrophy is an important risk factor of cardiovascular complications during the course of hypertension. Increased QT dispersion is associated with sudden cardiac death in congestive heart failure and in other cardiovascular diseases. Our aim was to compare QT dispersion from routine ECG in hypertensive patients with and without left ventricular hypertrophy defined by echocardiography. Authors examined 71 hypertensives treated in our medical department. Left ventricular hypertrophy was defined by echocardiography (Penn convention) as left ventricular mass index > 134 g/m2 in men and > 110 g/m2 in women. QT dispersion was defined from routine ECG (QTmax - QTmin). Presence of LVH was found in 26 patients (mean age 59.3 years), absence of LVH in 45 patients (mean age 57.8 years). Hypertensives with secondary hypertension, hypertrophic cardiomyopathy, sings of ischemia in ECG, arrhythmias, myocardial infarction, heart failure, diabetes mellitus and patients treated by antiarrhythmic drugs of the Ic and III groups were excluded. Both groups of hypertensives were matched by demographic parameters, and by the presence of hypertension, obesity, hyperlipidemia and smoking habites. There were statistically significant longer QT dispersion and QTc dispersion (59.0 +/- 20.1 ms, 64.0 +/- 23.7 ms) in LVH-positive patients than in LVH-negative once (43.2 +/- 9.5 ms, 48.4 +/- 11.1 ms). Left ventricular hypertrophy in patients with hypertension brings usually a complicated course of the disease. Authors recommend to look after left ventricular hypertrophy presence in hypertensives as it carries much more complicated course of the disease. Measurment of QT dispersion adds farther stratificational information to these patients.
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PMID:[QT dispersion intervals in hypertensives with left ventricular hypertrophy]. 1563 64

The causes of sudden cardiac death are diverse and are function of age. In young people, coronary anomalies, hypertrophic cardiomyopathy are the most common findings at autopsies; in adults, coronary atherosclerosis and acquired forms of cardiomyopathy are frequent findings. In many of non-ischemia related cases autopsies are unrevealing. One of the most frustrating challenges is the inability to determine the cause of death in a person previously healthy. The majority of such sudden deaths are caused by acute ventricular tachyarrhythmias, but unfortunately unassociated with structural injury to the heart. The present work evaluates incidence, clinical data, and laboratory tests. Biochemical studies on serum, pericardial fluid, vitreous humour and pathological characteristics of 38 cases of sudden cardiac death from 2003 were investigated by us. Also, non-cardiac natural causes of death must be excluded.
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PMID:Sudden death: correlation histopathological and biochemical. 1563 80


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