UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiac interstitium is composed of nonmyocyte cells and a structural protein network which plays a dominant role in governing the structure, architecture, and mechanical behavior of the myocardium. The heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for myocardial collagen metabolism and fibrous tissue accumulation, may largely explain the appearance of diastolic and/or systolic myocardial failure. Regulatory mechanisms that are related to the fibrous tissue response in various cardiovascular diseases, e.g., hypertensive heart disease, dilated cardiomyopathy or post myocardial infarction, are of primary clinical interest. A better understanding of the hitherto neglected role of cardiac fibroblasts in mediating an adverse structural remodeling of the myocardium will lead to specific pharmacologic agents that interfere with the fibrous tissue response. Several lines of evidence based on in vivo and in vitro studies suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition or aldosterone receptor antagonism that was found to prevent myocardial fibrosis in the rat with renovascular or genetic hypertension. In cultured adult cardiac fibroblasts, an angiotensin (Ang)II- or aldosterone-mediated dose-dependent increase in collagen synthesis could be completely abolished by the use of AngII type 1 or mineralocorticoid receptor antagonists, respectively. Likewise, the AngII-mediated decrease in the activity of matrix metalloproteinase 1, the key enzyme for interstitial collagen degradation, could be antagonized by AngII receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological modulation of cardiac fibroblast function. 777 64

Despite the findings in randomized trials of a significant effect of angiotensin-converting enzyme (ACE) inhibitors in reducing morbidity and mortality of patients with symptomatic left ventricular dysfunction, the morbidity and mortality of these patients remains relatively high. One potential strategy to further improve morbidity and mortality in these patients is blockade of a aldosterone. Many clinicians have assumed that ACE inhibitors would block both angiotensin II and aldosterone. However, there are data to suggest that aldosterone production may "escape" despite the use of an ACE inhibitor. An escape of aldosterone production has several important consequences, including: sodium retention, potassium and magnesium loss, myocardial collagen production, ventricular hypertrophy, myocardial norepinephrine release, endothelial dysfunction, and a decrease in serum high density lipoprotein cholesterol. Due to the potential importance of these mechanisms, the finding that there is a significant correlation between aldosterone production and mortality in patients with heart failure, as well as evidence that an aldosterone antagonist, spironolactone, when administered to patients with heart failure treated with conventional therapy including an ACE inhibitor results in increased diuresis and symptomatic improvement, an international prospective multicenter study has been organized, the Randomized Aldactone Evaluation Study (RALES Pilot Study), to evaluate the safety of blocking the effects of aldosterone in patients with heart failure treated with an ACE inhibitor.
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PMID:"Escape" of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. 778 35

Left ventricular hypertrophy (LVH) is a common consequence of hypertension, and an independent risk factor for cardiovascular morbidity and mortality. The presence and severity of LVH is best determined by echocardiography and expressed as left ventricular mass index or left ventricular wall thickness. Pathological LVH, in response to pressure or volume load on the heart, is characterised by myocyte hypertrophy and hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. Angiotensin II and aldosterone are promoters of increased fibroblast activity and a significant increase in collagen fibres in the myocardium. Early diagnosis and treatment of hypertension has significantly decreased the incidence of LVH and subsequent heart failure in many countries, but the choice of antihypertensive therapy alters the rate of reversal of LVH and the subsequent development of heart failure. Angiotensin converting enzyme (ACE) inhibitors, beta-blockers and calcium channel blockers produce the most rapid reversal of hypertrophy. Meta-analysis of these many small trials suggests an advantage of ACE inhibitors over other groups of antihypertensive agents.
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PMID:Hypertrophy to failure. 780 8

To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted.
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PMID:Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. 786 Jul 46

Allergic granulomatosis (Churg-Strauss) is sometimes associated with cutaneous manifestations. Biopsies of these manifestations are characteristic enough to allow for the diagnosis of this disease through histological examination. Case 1 involved a 34-year-old man who developed a low-grade fever, blood eosinophilia, paralysis of the right oculomotor nerve, and a polymorphic eruption. In addition, he suffered from preceding asthma and paresthesia of the legs and eventually developed heart failure. The histological examination of a biopsy taken from a hemorrhagic bulla showed a dense perivascular infiltration of eosinophils in the upper dermis and basophilic degeneration of collagen fibers. Case 2 involved a 41-year-old man who was afflicted with urticarial erythemas, livedoid erythemas, preceding asthma, and blood eosinophilia. During the course of his illness, he also developed bilateral peroneal nerve paralysis and two small erythemato-bullous lesions. The histological examination of a urticarial lesion revealed an abundant eosinophil perivascular infiltration; examination of a nodule revealed basophilic degeneration with a granulomatous reaction. Clinical and laboratory studies strongly suggested the diagnosis of allergic granulomatosis in both of these cases. The diagnosis was also supported by a histological examination of the skin lesions.
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PMID:Allergic granulomatosis (Churg-Strauss) associated with cutaneous manifestations: report of two cases. 789 25

The contractile function of the myocardium is coordinated by a fibrous matrix of exquisite organization and complexity. In the normal heart, and apparently in physiological hypertrophy, this matrix is submicroscopic. In pathological states changes are frequent, and usually progressive. Thickening of the many elements of the fine structure is due to an increased synthesis of Type I collagen, This change, which affects the myocardium in a global manner, can be observed by light microscopy using special techniques. Perivascular fibrosis, with an increase in vascular smooth muscle, is accompanied by development of fibrous septa, with a decrease in diastolic compliance. These structural changes are believed to be due to increased activation of the renin-angiotensin-aldosterone system, and to be independent of the processes of myocyte hypertrophy. Reparative or replacement fibrosis is a separate process by means of which small and large areas of necrosis heal, with the development of coarse collagen structures, which lack a specific organizational pattern. Regarding ischemic heart disease, an increase in tissue collagenase is found in experimental myocardial "stunning" and in the very early phase of acute infarction. Absence of elements of the fibrous matrix allow for myocyte slippage, and--if the affected area is large--cardiac dilatation. If, subsequently, the necrosis becomes transmural, there is further disturbance of collagen due to both mechanical strain and continued autolysis, During healing collagen synthesis increases greatly to allow for reparative scarring in the available tissue matrix. In cases of infarction with moderate or severe initial dilatation, pathological hypertrophy of the spared myocardium is progressive, accounting for late heart failure and poor survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Left ventricular dysfunction in ischemic heart disease: fundamental importance of the fibrous matrix. 794 72

The clinicopathologic findings of 23 patients with cardiac fibroma are presented. The mean patient age was 13 years, with a range of 1 day to 56 years. The presenting symptoms included heart failure, arrhythmias, sudden death, cyanosis, and chest pain. Some patients had no symptoms, and one patient had Gorlin's syndrome. Echocardiography and magnetic resonance imaging were very sensitive in diagnosis. Nineteen patients underwent tumor resection or biopsy, and four tumors were diagnosed at cardiac transplantation or autopsy on explanted hearts. In five surgical cases, complex operations were necessary, including pericardial or synthetic patches, valve replacement, or coronary artery grafting. Two operative deaths occurred in patients with surgical resections and four operative deaths in patients who at the time of the operation were deemed to have inoperable disease and only biopsy was performed. All deaths but one were in patients younger than 2 years of age. Four patients with subtotal resections did well after the operation. Dense collagen was more frequent in tumors in older patients. We conclude that fibromas are congenital tumors that are frequently discovered in adolescents and adults. Surgical treatment is generally successful, and imaging techniques are helpful in preoperative assessment.
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PMID:Cardiac fibroma: clinicopathologic correlates and surgical treatment. 796 68

The failing heart is characterized by impaired cardiac muscle function and increased interstitial fibrosis. Our purpose was to determine whether the functional impairment of the failing heart is associated with changes in levels of mRNA encoding proteins that modulate parameters of contraction and relaxation and whether the increased fibrosis observed in the failing heart is related to elevated expression of genes encoding extracellular matrix components. We studied hearts of 18- to 24-month-old spontaneously hypertensive rats with signs and symptoms of heart failure (SHR-F) or without evidence of failure (SHR-NF) and of age-matched normotensive Wistar-Kyoto (WKY) rats. Compared with WKY rats, SHR-NF exhibited left ventricular (LV) hypertrophy (2.2-fold) and right ventricular (RV) hypertrophy (1.5-fold), whereas SHR-F were characterized by comparable LV hypertrophy (2.1-fold) and augmented RV hypertrophy (2.4-fold; all P < .01). Total RNA was isolated from ventricles and subjected to Northern blot analysis. In SHR-F hearts, the level of alpha-myosin heavy chain mRNA was decreased in both ventricles to 1/3 and 1/5 of the SHR-NF and WKY values, respectively (both P < .01). Levels of beta-myosin heavy chain, alpha-cardiac actin, and myosin light chain-2 mRNAs were not significantly altered in hearts of SHR-NF or SHR-F. Levels of alpha-skeletal actin were twofold greater in SHR-NF hearts compared with WKY hearts and were intermediate in SHR-F hearts. Levels of atrial natriuretic factor (ANF) mRNA were elevated threefold in the LV of SHR-NF (P < .05) but were not significantly increased in the RV of SHR-NF compared with WKY rats. During the transition to failure (SHR-F versus SHR-NF), ANF mRNA levels increased an additional 1.6-fold in the LV and were elevated 4.7-fold in the RV (both P < .05). Levels of sarcoplasmic reticulum Ca(2+)-ATPase (SRCA) mRNA were maintained in the LV of hypertensive and failing hearts at levels not significantly different from WKY values. In contrast, the level of RV SRCA mRNA was 24% less in SHR-NF compared with WKY rats, and during the transition to failure, this difference was not significantly exacerbated (29% less than the WKY value). The levels of fibronectin and pro-alpha 1(I) and pro-alpha 1(III) collagen mRNAs were not significantly elevated in either ventricle of the SHR-NF group but were fourfold to fivefold higher in both ventricles of SHR-F (all P < .05).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure. Marked upregulation of genes encoding extracellular matrix components. 801 79

In the progression from myocardial hypertrophy to heart failure, abnormalities in the interstitial space of the heart seem to play a critical role. The formation of an extracellular oedema and the alterations in coronary subendocardial perfusion are associated with the development of interstitial fibrosis. Cardiac experimental studies documented the presence of augmented interstitial fluid volume and pressure and a subsequent remodelling of the fibrillar network of the extracellular space of the myocardium during the phases of the cardiovascular response to a sudden overload. Variations of the Starling's forces balance caused by enhanced endothelial permeability or due to an impairment of cardiac lymphatic drainage may contribute to the development of an acute heart failure. During stable hyperfunction, the organization of a chronic oedema should account for interstitial changes in the hypertrophic myocardium. Reactive fibrosis seems to be under hormonal control. The activation of the renin-angiotensin-aldosterone system is responsible for interfascicular and intercellular accumulation of fibrillar collagen within the cardiac interstitium. Perivascular fibrosis in the subendocardium may impair intramyocardial distribution of coronary flow. When an inadequate hypertrophy occurs, because of an elevation in ventricular wall stress, myocardial oxygen consumption rises and this may lead to the exhaustion of coronary blood flow reserve in the subendocardial layers. This underperfusion may be responsible for the development of myocardial ischemia. Coronary hemodynamic changes in the microcirculation as those prompted by interstitial alterations may contribute to the onset of myocyte necrosis and to the formation of restorative fibrosis. The progressive mechanical overload of the spared hypertrophied myocytes could explain the initiation of a positive feedback mechanism which perpetuates endomyocardial perfusion impairment, interstitial oedema and remodelling, finally, causing myocyte deaths and fibrous tissue proliferation. These structural alterations and their pathophysiological counterparts appear to be closely related to the evolution from compensatory hypertrophy to chronic myocardial failure in hypertrophic heart disease.
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PMID:[From myocardial hypertrophy to heart failure: role of the interstitium]. 802 50

Cardiac fibrosis is one of the deleterious events accompanying hypertension that may be implicated in the progression toward heart failure. To determine the mechanisms involved in fibrosis and the role of hemodynamic versus humoral factors, we studied the expression of genes involved in hypertrophy and fibrosis in the heart of rats treated with aldosterone for 2 months with addition of 1% NaCl and 0.3% KCl in water. This treatment induced arterial hypertension, a moderate left ventricular hypertrophy, and a decrease in plasma thyroxine. Equatorial sections of hearts from treated rats showed numerous foci of proliferating nonmuscular cells and a biventricular fibrosis. Computerized videodensitometry demonstrated an increase of collagen volume fraction by 152% and 146% and of the ratio of the perivascular collagen area and vascular area by 86% and 167% in left and right ventricles, respectively. As measured by slot blot, this cardiac fibrosis was accompanied by an increase in alpha 1-I procollagen mRNA by 75% and 160% (P < .01) and in alpha 1-III mRNA by 76% and 319% (P < .01) in left and right ventricles, respectively. Atrial natriuretic peptide mRNA was induced only in the hypertrophied left ventricle. We conclude that fibrosis is occurring and involves pretranslational regulation of collagen synthesis. Whereas hypertrophy and atrial natriuretic peptide mRNA increase are restricted to the left ventricle, fibrosis is initiated in both ventricles, supporting the hypothesis that this cardiac response is independent of hemodynamic factors.
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PMID:Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension. 802 Oct 5

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