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PubMed1995

[Interactions between cardiomyocytes and extracellular matrix in the failing human heart].

Numerous morphological changes can be observed in human myocardium failing because of dilated cardiomyopathy. These can be observed by electron microscopy and by immunofluorescence microscopy using monoclonal antibodies. These changes include: 1) the occurrence of hypertrophied and atrophied myocytes as well as cells of normal size, 2) degenerative changes in myocytes; these consist of nuclei of varying size and shape, lack of contractile material, disorganization of the cytoskeleton, and sequestration of cellular particles into the extracellular space and 3) an enlarged extracellular space, that is, fibrosis, which contains increased amounts of the different matrix proteins such as fibronectin and laminin, the various collagens, and chondroitin sulfate, in addition to cellular debris and numerous macrophages and fibroblasts. On the basis of these findings it is hypothetized that there exists an interaction between myocytes and the extracellular matrix. The cells of the latter may be stimulated to higher rates of proteins synthesis by the presence of cellular debris. This process, in turn, may be harmful for the structural integrity of myocytes which consequently sequester more cellular particles. In this manner, a vicious circle may be started that leads to further structural and functional deterioration of the myocardium, finally resulting in failure.

Cardiomyopathy, Dilated↗
PubMed1984

Computer-assisted quantitation of myocardial fibrosis in histologic sections.

Histologic characterization of the myocardium may require estimation of the collagen content of the specimen. A computer-assisted method can be used to determine collagen content from histologic sections. Full-thickness segments of normal or fibrotic left ventricular myocardium from ten human hearts were divided into portions for hydroxyproline assay and for trichrome staining of histologic sections. The sections were digitized using a computerized video analysis system and were segmented into collagen and muscle regions using a gray-level threshold technique that yielded an estimate of the percent of collagen. A wide range of collagen content, from normal (5 micrograms of hydroxyproline per milligram of dry weight) to fibrotic (38 micrograms/mg) myocardium, was studied. The percentage of collagen from analysis of histologic sections strongly correlated with the hydroxyproline level, with excellent intraobserver and interobserver concordance. Results were unaffected by variations in histochemical staining.

Adolescent↗
PubMed1985

[2 families with dilatative cardiomyopathy].

In two brothers each of two families congestive cardiomyopathy was diagnosed. Left ventricular biopsy showed individually differing degrees of hypertrophy of the myocardial cells together with endocardial fibrosis and circumscribed interstitial fibrosis. In family I clinical symptoms appeared at the beginning of the 4th decade, conduction disturbances being predominant. One brother died after rapid progression of the disease within one year. The other has been treated as an outpatient for 9 years; he received a pacemaker implant half a year ago. In family II initial symptoms appeared in the middle of the 6th decade, progressive heart dilation and insufficiency being the predominant characteristics. In the course of 7 years one brother has developed cardiac decompensation whereas the other brother's condition has remained nearly unchanged for 4 years. The degree of myocardial changes in left ventricular biopsies correlated with the clinical course.

Adult↗
PubMed2004

Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.

Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, P<0.01). The reduction of interstitial fibrosis is accompanied by an increase in myocardial hHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.

Apoptosis↗
PubMedDate not supplied

Ischemic myocardial contracture ("stone heart"). A complication of cardiac surgery.

Stone heart or ischemic myocardial contracture is a complication of cardiopulmonary bypass characterized by contracture of the myocardium and inability to obtain cardiac output on manual massage. Stone heart has occurred only during aortic valve replacement and/or coronary artery bypass procedures. Predisposing factors are chronic congestive heart failure and myocardial hypertrophy with fibrosis secondary to longstanding aortic valve disease and/or coronary artery occlusive disease. Although the condition is rare, the outcome is usually fatal. Because of the biochemical and physiological implications of this syndrome, its prevention has been challenging. On the basis of our current concepts, prevention has been afforded by topical and general hypothermia and pretreatment with a small i.v. bolus of propranolol just prior to aortic occlusion. These measures have been utilized in potentially high-risk patients with the predisposition for stone heart and, thus far, the results have been satisfactory. The stone heart syndrome is an entity which should be recognized by all cardiac surgeons. Preventive measures must be aimed at protection of the myocardium during anoxic cardiac arrest.

Cardiac Output↗
PubMed1992

Right ventricular dysplasia: morphological findings in 13 cases.

OBJECTIVE: To characterize the pathological features of right ventricular dysplasia (RVD). DESIGN: Retrospective morphological case study. SETTING: Three referral-based university medical centres. PATIENTS: Thirteen subjects (one female) aged 16 to 55 years including 10 necropsy hearts from sudden deaths out of hospital, one explant heart and two partial right ventricular resections from patients with intractable ventricular tachycardia. MAIN RESULTS: Most hearts showed hypertrophy and localized or generalized dilatation of the right ventricle. Transillumination revealed myocardial thinning of variable configuration usually conforming to regions of dilatation. Common sites of involvement were apex, infundibular region and posterobasal wall. Histologically, focal or extensive segments of right ventricular myocardium were absent or replaced. Three patterns were found: right ventricle markedly thinned, epicardium and endocardium contiguous, virtually no intervening tissue; wall normal thickness or thinned, myocardium almost totally replaced by fat; and wall normal or thin, myocardium largely replaced by fat with scattered residual myocardial cells and fibrous tissue (the predominant pattern). Endocardial fibrosis was present in eight cases and focal mononuclear cell infiltrates in 10. Electron microscopy in two cases showed nonspecific findings. CONCLUSIONS: RVD has gross and microscopic features which permit its recognition. While a majority of cases are likely congenital (genetic or acquired in utero), the possibility of postnatally acquired conditions (inflammatory, toxic, ischemic) inducing RVD must be explored. The incidence and importance of RVD as a cause of sudden death can only be assessed by continued systematic and detailed studies of patients with recurrent ventricular tachycardia and of hearts, especially from sudden death victims. Although uncommon, RVD should be considered in the differential diagnosis of arrhythmia and sudden death by both clinicians and pathologists.

Adolescent↗
PubMed1991

Progressive cardiac fibrosis and myocyte injury in v-fps transgenic mice. A model for primary disorders of connective tissue in the heart?

Transgenic mice that express v-fps protein-tyrosine kinase have severe cardiac or neurologic abnormalities and a high incidence of lymphoid or mesenchymal tumors. The cardiac lesions of v-fps transgenic mice were examined at less than 1, 2, 3, 6, 14, 26, and 43 weeks of age (total N = 19) and compared with nontransgenic littermate controls (N = 34). Three of eight transgenic animals 1 to 4 days old showed moderate proliferation of connective tissue elements most evident along the septal endocardium of the right ventricle. Variable cardiac hypertrophy was seen grossly in 2- to 14-week-old transgenic animals, and marked biventricular dilatation was present in those 6 to 43 weeks of age. Sections of all transgenic mice 3 weeks or older revealed characteristic lesions that consisted of cellular fibrosis in subendocardial, subepicardial, and perivascular sites, with associated proliferation of pericytes and fat cells. Atrophy, degeneration, and loss of entrapped myocytes were noted in transgenic animals as early as 2 weeks of age, but frank coagulative necrosis or myocytolysis was absent at all ages studied. Nonetheless, pleomorphic nuclei were found in occasional myocytes late in disease. Inflammatory cells were rare, as confirmed immunohistochemically (Thy-1 [pan-T], L3T4 [CD4], Lyt-2 [CD8], interleukin-2 receptor [activated lymphocyte], Mac-1 [macrophage], and B220 [pan-B]). Monoclonal immunoreactivity to the v-fps transgene product was positive predominantly in nonmyocyte cardiac constituents. Collectively, the data suggest a primary proliferative abnormality of connective tissue elements in the heart, accompanied by secondary myocyte damage.

Aging↗
PubMed2005

Relaxin and the extracellular matrix: molecular mechanisms of action and implications for cardiovascular disease.

Myocardial fibrosis is a common endpoint in a variety of cardiac pathologies. It results from excessive accumulation of collagen and other materials that together comprise the extracellular matrix (ECM). In the past decade, the peptide hormone relaxin has emerged as an important regulator of the ECM within several organs, including the heart, and has been suggested as a novel therapeutic agent for the treatment of fibrotic disorders. This review summarises research on the anti-fibrotic actions of relaxin, outlines the potential mechanisms by which relaxin regulates the ECM in cardiovascular tissues and examines the implications of this research for the management of heart disease. Some of the contradictions in the literature are also addressed in order to clarify the role of relaxin as an anti-fibrotic factor in vivo.

Animals↗
PubMed1992

Coronary artery operation in radiation-associated atherosclerosis: long-term follow-up.

Radiation-associated coronary atherosclerosis is a potential problem for patients who have had mediastinal irradiation for malignant tumors. This study identified 14 patients with radiation-associated coronary atherosclerosis, defines unique population characteristics, and analyses postsurgical problems and long-term outcome. Fourteen patients with radiation-associated coronary atherosclerosis and class III and IV New York Heart Association symptoms were identified because of mediastinal or chest wall irradiation (30 Gy) associated with anterior epicardial discoloration or fibrosis, aortitis with adventitial thickening, and inflammatory process over a proximal coronary artery. Two distinct treatment groups were analyzed. Coronary artery operation resulted in one hospital death, with vein grafts being used predominantly. The internal mammary artery could only be used in 3 patients because of vessel friability and mediastinal fibrosis. Postoperative right ventricular dysfunction and pulmonary problems were frequent. Severe pericardial inflammatory complications (fibrosis with graft closure, and constrictive pericarditis) present in 2 early patients resulted in routine anterior pericardiectomy after coronary artery operation without further problems. Long-term follow-up (100%) (range, 11 to 74 months) revealed that 1 patient died late and of the remainder (12 patients), 11 were in New York Heart Association class I and 1 in class II, experiencing three myocardial events. Thus, patients with radiation-associated coronary atherosclerosis have a low operative mortality but have risk of early right ventricular and pulmonary dysfunction. The routine use of internal mammary artery may not be possible and anterior pericardiectomy is recommended. Long-term results are excellent and no evidence of accelerated disease has been noted.

Adult↗
PubMed2003

Remodeling of the cardiac extracellular matrix differs between volume- and pressure-overloaded ventricles and is specific for each heart valve lesion.

BACKGROUND AND AIM OF THE STUDY: Different patterns of fibroblast-mediated remodeling of the extracellular matrix (ECM) might be expected between patients with pressure- and volume-induced left ventricular hypertrophy. METHODS: Patients with chronic pressure-overload due to aortic stenosis (AS, n = 19) and chronic volume-overload due to either aortic regurgitation (AR, n = 9) or mitral regurgitation (MR, n = 10) were examined. The amount of interstitial collagen was quantified by using circular-polarization-microscopy in picrosirius red-stained biopsies. Biopsies from 10 patients with mild cardiomyopathy served as controls. In a subgroup, collagen type-I (Coll-I) and collagen type-III (Coll-III) gene expression was evaluated by quantitative RT-PCR. After immunohistological staining, procollagen-I/procollagen-III ratio and density of fibroblasts (FB) per vision-field were analyzed. RESULTS: The amount of interstitial cardiac fibrosis (ICF) was significantly higher in AS (5.7 +/- 4.1 g/m2), AR (8.8 +/- 4.9 g/m2) or MR (4.7 +/- 2.8 g/m2) than in controls (2.3 +/- 1.5 g/m2) (p = 0.003). The amount of thick collagen fibers was higher in AR than in AS, where-by density of fibroblasts did not differ. In volume-overloaded ventricles, the Coll-I/Coll-III ratio was shifted towards Coll-I, and in pressure-overloaded ventricles towards Coll-III. The severity of ECM remodeling was positively correlated with wall stress and impaired diastolic function, but not with systolic function or clinical symptoms. CONCLUSION: Remodeling of the ECM is specific for left ventricular volume and pressure overload, and may serve as an early indicator for inadequate adaptation.

Adult↗
PubMed1985

The degree to which myocardial infarct site and size determine the electrocardiographic axis. Analysis of correlative data by computational modeling.

The spatial electrical QRS axis was determined for 428 twelve-lead electrocardiograms from patients subsequently shown by postmortem dissection to have ventricular myocardial fibrosis or necrosis. Four 16-segment ventricular models of the heart were used to "predict" the spatial electrical QRS axis from known ventricular mass and deficit. The raw model I in ideal anatomic position and vectors perpendicularly outward for each muscle segment showed a mean correlation value of -0.494; model II was rotated in the chest to produce best fit with a correlation of 0.638, but the anatomic orientation was not reasonable; model III maintained original position and orientation but the vectors were scaled (correlation 0.780); and model IV, with nonperpendicular vectors, yielded a mean correlation of 0.793. The exceptions to good predictability formed a distinct subset largely composed of electrocardiograms with some form of variant intraventricular conduction (slight QRS widening, fascicular block patterns and "indeterminate frontal-plane axis").

Electrocardiography↗
PubMed2002

Remodeling of small intramyocardial coronary arteries distal to a severe epicardial coronary artery stenosis.

OBJECTIVE: Impaired coronary blood flow (CF) or flow reserve with incomplete and delayed recovery of left ventricular (LV) function after revascularization is common in severe ischemic LV dysfunction. The underlying mechanism is not fully known. We studied structural changes of small intramyocardial coronary arteries (SIMCAs) in a pig model of chronic coronary stenosis, testing the hypothesis that microvascular remodeling develops distally to a severe epicardial coronary artery stenosis. METHODS AND RESULTS: A total of 24 pigs were studied in 3 groups. Left anterior descending coronary stenosis was created to reduce CF by a mean of approximately 30%, producing severe regional systolic dysfunction without infarction. The stenosis was maintained for 7 days in 6 pigs (Group 1) and for 4 weeks in 12 pigs (Group 2). The control group (Group 3) consisted of 6 pigs with the same surgical procedures but without stenosis. The wall thickness (WTa) and lumen (L) diameter of SIMCA were measured, and the ratio of WTa/L and lumen area/total vessel area (% lumen) were calculated. The composition of the arterial wall was studied with cell proliferation markers Ki67 and BrdU. The immediate reduction in CF after the creation of the stenosis was similar in both study groups, but after the first week, CF decreased significantly (P<0.05) when the stenosis was maintained (group 2). The left anterior descending stenosis caused regional LV dysfunction in all pigs (groups 1 and 2). After 4 weeks of stenosis with chronic myocardial hibernation (group 2), but not after 1 week (group 1), WTa and WTa/L increased and L decreased significantly in the chronic hibernating region located distally to the stenosis, compared with both the control (group 3) and the normal region in the same pig. The mean % lumen of SIMCA per pig correlated with the CF reduction (r=0.92, P<0.001) and with myocardial fibrosis (r=0.82, P<0.01) in the 4-week stenosis group. Ki67- and BrdU-positive cells were increased in the wall of SIMCA in Group 1 and 2 compared with the control group (P<0.01 for each). The proliferated cells were stained positively with smooth muscle alpha-actin antibody. CONCLUSION: In the chronic ischemic, hibernating myocardial region distal to a flow-limiting epicardial coronary stenosis, the small intramyocardial coronary arteries undergo remodeling, with an increase in wall thickness and a decrease in lumen. These structural changes may further restrict blood flow to ischemic myocardium and may account for the pathophysiologic impairment of CF or flow reserve after revascularization, which leads to delayed or incomplete recovery of myocardial function.

Animals↗
PubMed1993

Pathophysiology and clinical aspects of hypertensive hypertrophy.

Individuals with hypertension and electrocardiographic (ECG) evidence of left ventricular hypertrophy (LVH) have a 10-fold greater risk of developing cardiac failure than hypertensives without ECG evidence of LVH. LVH in hypertension is characterized by myocardial fibrosis and structural changes to the small intramural arteries. Hypertensives with or without LVH have reduced coronary vasodilator reserve due to hypertensive disease of small coronary arteries. Prognosis of arterial hypertension is largely determined by cardiac complications. The aim of treatment of hypertensive heart disease is to reverse myocardial hypertrophy in order to prevent progression to hypertensive heart failure, as well as reversal of the hypertensive disease of small coronary arteries in order to improve coronary reserve. On the development of hypertensive heart failure, administration of digitalis, diuretics and angiotensin converting enzyme (ACE) inhibitors should be initiated. Although regression of LVH can be induced by dihydropyridine calcium channel blockers, ACE inhibitors and sympatholytic substances, clinical evidence of the reversal of hypertensive disease of small coronary arteries has still to be established.

Adrenergic beta-Antagonists↗
PubMed1995

Feline endomyocarditis and left ventricular endocardial fibrosis.

A retrospective study was conducted of all feline necropsies over a 7-year period. Of a total of 1,472 necropsies, 37 cases of endomyocarditis (EMC) and 25 cases of left ventricular endocardial fibrosis (LVEF) (previously called restrictive or intermediate cardiomyopathy) were identified. There was a subset of four cats with EMC that had histologic features of both diseases. Interstitial pneumonia was seen in 25 of 35 cats (71%) with EMC but in only seven of 25 cats (28%) with LVEF. Thrombi or thromboemboli were seen in 14 of 25 cats (56%) with LVEF but in only six of 37 of cats (16%) with EMC. In both LVEF and EMC, thromboemboli were located in the abdominal aorta, left atrium and ventricle of the heart, femoral artery, cranial mesenteric artery, liver, pulmonary artery, jugular vein, or a meningeal vessel. Each cat had a single thrombus/thromboembolus, except for four cats with LVEF that had more than one. The histologic and clinical findings suggest that EMC and LVEF represent temporally different manifestations of a single disease entity.

Animals↗
PubMed2004

Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese Zucker rats.

Diabetes has a markedly greater incidence of cardiovascular disease than the non-diabetic population. The heart shows a slowly developing increase in fibrosis in diabetes. Extended cardiac fibrosis results in increased myocardial stiffness, causing ventricular dysfunction and, ultimately, heart failure. Reversal of fibrosis may improve organ function survival. Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and cardiovascular complications, and has been proposed as an independent risk factor for cardiovascular diseases. Salacia oblonga (S.O.) is traditionally used in the prevention and treatment of diabetes. We investigated the effects of its water extract on cardiac fibrosis and hyperglycemia in a genetic model of type 2 diabetes, the obese Zucker rat (OZR). Chronic administration of the extract markedly improved interstitial and perivascular fibrosis in the hearts of the OZR. It also reduced plasma glucose levels in non-fasted OZR, whereas it had little effect in the fasted animals, suggesting inhibition of postprandial hyperglycemia in type 2 diabetic animals, which might play a role in improvement of the cardiac complications of OZR. Furthermore, S.O. markedly suppressed the overexpression of mRNAs encoding transforming growth factor betas 1 and 3 in the OZR heart, which may be an important part of the overall molecular mechanisms. S.O. dose-dependently inhibited the increase of plasma glucose in sucrose-, but not in glucose-loaded mice. S.O. demonstrated a strong inhibition of alpha-glucosidase activity in vitro, which is suggested to contribute to the improvement of postprandial hyperglycemia.

Analysis of Variance↗
PubMed1993

Protective effect of clentiazem against epinephrine-induced cardiac injury in rats.

We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway.

Animals↗
PubMed2001

Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship.

Cardiac extracellular matrix undergoes extensive and continuous turnover involved in the lesion-reparation process, such as in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardial infarction in the transition to heart failure, and during the progression of left ventricular dysfunction. Cardiac fibrosis is a major determinant of diastolic dysfunction and pumping capacity, and it may provide the structural substrate for arrhythmogenicity, thus potentially contributing the to progression of heart failure and sudden death. Aldosterone was shown to promote cardiac fibrosis in various experimental models. It was demonstrated that spironolactone may oppose the effect of aldosterone in promoting cardiac fibrosis. Measurement of cardiac collagen turnover by use of serological markers is a useful tool for monitoring cardiac tissue repair and fibrosis in experimental models or clinical conditions. We found that high serum levels of a marker of collagen turnover (procollagen type III N-terminal peptide ) in patients with chronic heart failure receiving conventional therapy, including ACE inhibitors, was associated with high mortality and hospitalization rates. In RALES (Randomized Aldactone Evaluation Study), in patients randomized to placebo, markers continued to increase or remained unchanged after 6-month follow-up. On the contrary, adding spironolactone 25 mg daily significantly decreased the levels of these serum markers during the same period. Most importantly, the spironolactone-related morbidity and mortality benefit was most predominant in subgroups with highest baseline levels of serum markers. These results suggest that limitation of the aldosterone-related excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with chronic heart failure.

Aldosterone↗
PubMed2001

Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure.

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified. METHODS: Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis. RESULTS: Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment. CONCLUSIONS: These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.

Aged↗