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)

Diastolic heart failure is characterized by increased resistance to diastolic filling of one or both cardiac ventricles. Although some degree of diastolic failure exists in most patients presenting clinically with heart failure, a substantial subset of patients have relatively pure diastolic heart failure with normal systolic function. Diastolic heart failure can be due to structural abnormalities that increase resistance to ventricular inflow, and these structural abnormalities can be extramyocardial (e.g., constrictive pericarditis and mitral stenosis) or intramyocardial (e.g., fibrosis and amyloidosis). In addition to structural abnormalities, physiological derangement of myocardial inactivation and relaxation can contribute importantly to diastolic dysfunction in patients with heart failure. There is mounting evidence that advanced myocardial hypertrophy is associated with increased resistance to ventricular diastolic inflow due to both structural alteration (increased wall thickness and altered collagen matrix) and impaired diastolic relaxation of the hypertrophied myocardium. Physiological mechanisms for impaired relaxation in advanced hypertrophy remain controversial but can include disordered function of myocardial sarcoplasmic reticulum, subendocardial ischemia, and altered adenylate cyclase function. Diastolic dysfunction can play an important role in the genesis of flash pulmonary edema seen in patients with ischemic heart disease because myocardial ischemia is associated with a decline in relaxation rate, increased resistance to early diastolic filling, and in some cases, a striking upward shift in the left ventricular diastolic pressure-volume relation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diastolic dysfunction and congestive heart failure. 213 51

Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF > 50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E > A), delayed relaxation (E < A), and restrictive (E >> A) filling patterns. Invasive assessment of diastolic function allows determination of the time constant of relaxation from the exponential pressure decay during isovolumic relaxation, and the evaluation of the passive elastic properties from the slope of the diastolic pressure-volume (= constant of chamber stiffness) and stress-strain relationship (= constant of myocardial stiffness). The prognosis of diastolic heart failure is usually better than for systolic dysfunction. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and AT2-blockers as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.
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PMID:Diastolic heart failure. 1072 7

Epidemiologic as well as clinical studies confirm the close link between diabetes mellitus and heart failure. Diabetic cardiomyopathy (DCM) is still a poorly understood "entity", however, with several contributing pathogenetic factors which lead in different stages of diabetes to characteristic clinical phenotypes. Hyperglycemia with a shift from glucose metabolism to increased beta-oxidation and consecutive free fatty acid damage (lipotoxicity) to the myocardium, insulin resistance, renin-angiotensin-aldosterone system (RAAS) activation, altered calcium homeostasis and structural changes from the natural collagen network to a stiffer matrix due to advanced glycation endproduct (AGE) formation, hypertrophy and fibrosis contribute to the respective clinical phenotypes of DCM. We propose the following classification of cardiomyopathy in diabetic patients: a) Diastolic heart failure with normal ejection fraction (HFNEF) in diabetic patients often associated with hypertrophy without relevant hypertension. Relevant coronary artery disease (CAD), valvular disease and uncontrolled hypertension are not present. This is referred to as stage 1 DCM. b) Systolic and diastolic heart failure with dilatation and reduced ejection (HFREF) in diabetic patients excluding relevant CAD, valvular disease and uncontrolled hypertension as stage 2 DCM. c) Systolic and/or diastolic heart failure in diabetic patients with small vessel disease (microvascular disease) and/or microbial infection and/or inflammation and/or hypertension but without CAD as stage 3 DCM. d) If heart failure may also be attributed to infarction or ischemia and remodeling in addition to stage 3 DCM the term should be heart failure in diabetes or stage 4 DCM. These clinical phenotypes of diabetic cardiomyopathy can be separated by biomarkers, non-invasive (echocardiography, cardiac magnetic resonance imaging) and invasive imaging methods (levocardiography, coronary angiography) and further analysed by endomyocardial biopsy for concomitant viral infection. The role of specific diabetic drivers to the clinical phenotypes, to macro- and microangiopathy as well as accompanying risk factors or confounders, e.g. hypertension, autoimmune factors or inflammation with or without viral persistence, need to be identified in each individual patient separately. Thus hyperglycemia, hyperinsulinemia and insulin resistance as well as lipotoxicity by free fatty acids (FFAs) are the factors responsible for diabetic cardiomyopathy. In stage 1 and 2 DCM diabetic cardiomyopathy is clearly a fact. However, precise determination of to what degree the various underlying pathogenetic processes are responsible for the overall heart failure phenotype remains a fiction.
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PMID:Diabetic cardiomyopathy--fact or fiction? 2142 47

Diastolic heart failure (DHF) is an important entity, the significance of which is increasingly recognized. This report examines the available evidence regarding the role, significance, and mechanisms of DHF. Epidemiologic studies have documented the rising burden of DHF, and experimental data are revealing the unique mechanisms distinguishing it from systolic heart failure. Despite controversies on the definition of DHF, or heart failure with preserved ejection fraction, standardized clinical criteria with supplementary imaging and structural data have identified DHF as a distinct pathophysiological entity. The mechanisms underlying DHF include abnormal matrix dynamics, altered myocyte cytoskeleton, and impaired active relaxation. The commonly held belief that survival of patients with DHF is better than that of patients with systolic heart failure has been challenged by updated data. The heterogeneous etiologies or risk factors for the condition include aging, diabetes, hypertension, and ischemia, making a common diagnostic or treatment pathway difficult. Novel therapeutic targets that address the pathophysiology of this disease are under consideration, although there are no proven therapies for DHF to date. Exacerbating factors include volume and sodium indiscretion, arrhythmias, ischemia, and comorbidities. Strategies to ameliorate or to obviate these precipitating factors are most effective in preventing DHF and its exacerbations. Meanwhile, prevention of DHF through appropriate and aggressive risk factor identification and management must remain the cornerstone of clinical intervention.
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PMID:Diastolic heart failure: progress, treatment challenges, and prevention. 2160 70