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

Immunization against components of the renin-angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel trade mark ) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel trade mark (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.
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PMID:Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects. 1510 32

The present paper reviews the pathophysiology and therapeutic strategies in heart failure based on clinical investigations performed in our institute, and also recently reported large-scale double-blind clinical trials for the medical treatments of heart failure. Careful introduction of beta-blocker therapy along with RAAS inhibitors (ACE inhibitor, ARB, and/or aldosterone antagonist) should bring about marked improvement in mortality and morbidity in all subgroups of patients with heart failure.
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PMID:[Back to the future: pathophysiology and therapeutic strategies in heart failure]. 1567 65

Congestive heart failure is a major clinical and public health challenge. With increased aging, and advanced care of almost all other cardiac diseases, myocardial failure has become the single most common reason for hospitalization for patients older than 65. Conventional wisdom addressed heart failure as a hemodynamic perturbation consisting of congestion and limited cardiac output. Efforts intuitively focused on augmenting systolic function and clearing excessive pulmonary and systemic edema. Despite symptomatic improvement, mortality and functional deterioration continued unabated. Afterload reducing therapy emerged as an effective modality of improving cardiac function. Selective targeting of renin-angiotensin-aldosterone system (RAAS) was shown to be superior to alternative nonhormone-based approaches. These clinical observations gave impetus to the neurohumoral paradigm of heart failure. Whereas attention to the congestive aspects of heart failure remains an essential component of therapy, it is by no means sufficient to neutralize the complex and interactive pathogenic mechanisms which underlie this syndrome. Particularly relevant, is the asymptomatic stage of ventricular dysfunction which portend significant future structural and functional deterioration. Mounting evidence confirm the benefit of ACEI and ARB in attenuating ventricular remodeling and improving survival. This paper aims at reviewing the evidence which has led to the strongly held paradigm of neurohormonal basis of heart failure. Appropriate and evidence based therapeutic strategies are presented.
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PMID:Congestive heart failure: new paradigms and therapeutic targets. 1570 79

The present study was undertaken to examine the effects of a calcium channel blocker, azelnidipine (1 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, temocapril (10 mg/kg/day), an angiotensin II type 1 (AT1) receptor blocker (ARB), olmesartan (5 mg/kg/day), and their combination on Dahl salt-sensitive rats (DS rats) developing heart failure with preserved systolic function. DS rats were fed a high-salt diet (8% NaCl) from 7 weeks of age and progressively developed hypertension. Although monotherapy with azelnidipine lowered the blood pressure of DS rats to a greater extent than monotherapy with temocapril or olmesartan, the three drugs had similar effects on cardiac hypertrophy, cardiac fibrosis, the expressions of brain natriuretic peptide, transforming growth factor-beta1, collagen I, collagen III and monocyte chemoattractant protein-1 mRNA (as estimated by Northern blot analysis), and cardiac diastolic dysfunction (as estimated by echocardiography). These results show that ACE and AT1 receptor, as well as hypertension, are involved in the development of heart failure with preserved systolic function in DS rats. The combination of azelnidipine with olmesartan or temocapril produced no additive hypotensive effect in DS rats and no additive effect on cardiac hypertrophy or gene expressions. However, the combination therapy prolonged the survival rate of DS rats more than azelnidipine (p <0.01) or temocapril alone (p <0.05), and this additive beneficial effect by the combination therapy was associated with a greater reduction of cardiac fibrosis, urinary albumin excretion and serum creatinine. Our results thus showed that the combination of a calcium channel blocker with an ARB or an ACE inhibitor had additive preventive effects on a rat model of hypertensive heart failure with preserved systolic function. Thus, combination therapy with these agents seems to be a useful therapeutic strategy for the prevention of hypertensive heart failure.
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PMID:Additive beneficial effects of the combination of a calcium channel blocker and an angiotensin blocker on a hypertensive rat-heart failure model. 1578 13

30-50% of patients presenting with symptoms of congestive heart failure exhibit a near normal left ventricular systolic function at rest, and an impaired diastolic function of the heart may be causative. Despite a better prognosis than in systolic heart failure, frequency of hospitalizations due to diastolic heart failure is comparable with systolic heart failure. According to the criteria of Vasan and Levy diagnosis of diastolic heart failure is probable, if symptoms and signs of heart failure are accompanied in proximity (within 72 h) by objective evidence of normal left ventricular systolic function. Newer echocardiographic techniques (e. g., tissue Doppler) aid to confirm the diagnosis and to determine the severity of dysfunction and may substitute invasive demonstration of impaired left ventricular relaxation, filling, compliance or stiffness for standardized diagnosis. Incorporation of biochemical test (BNP [brain natriuretic peptide]) allows differential diagnosis and may increase the accuracy of diagnosis. Due to inconsistent diagnostic criteria, data from prospective randomized controlled trials for the treatment of diastolic heart failure are rare. Basic principles include treatment of the underlying disease, i. e., control of hypertension, diabetes, or obstructive airway disease. Angiotensin 1 antagonists (ARB) have proven effective in regression of left ventricular hypertrophy (LIFE) and may reduce morbidity, but not mortality (CHARM). Maintenance of sinus rhythm, heart rate control (beta-blockers, calcium channel blockers) and anti-ischemic therapy may be indicated in view of pathophysiological aspects. Diuretics should be administered with caution in patients with symptoms of congestion, digitalis is not useful in the treatment of isolated diastolic heart failure. The results of ongoing trials (e. g., I-Preserve) may offer new therapeutic options, and evidence-based guidelines for the so far often unsatisfactory treatment of diastolic dysfunction/heart failure are awaited.
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PMID:[Dyspnea and normal systolic function]. 1591 35

The benefits of reducing blood pressure (BP) on the risks of major cardiovascular event and preservation of renal function are well established in patients with hypertension. We estimated effects of strategies based on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) and calcium channel antagonist (CCB), which is predominantly prevalent in Japan in patients with hypertenstion than ACEI/ARB, on the risks of these events, overviewed with data from clinical trials and meta-analysis of these trials including underwent in Japan. ACEI and ARB-based regimens reduced the risks of heart failure and progression of renal dysfunction complicated with and without diabetes mellitus (DM) in patients with hypertension compared with control and CCB-based regimens. CCB-based regimens reduced the primary risks of cerebella event and dementia and primary and secondary risks of coronary events in patients with hypertension having many coronary risk factors compared with control and ARB/ACEI-based regimens. Greater risk reductions, however, were produced by regimens that targeted lower (BP) goals, by combined regimens based on ACEI/ARB and CCB and diuretics, demonstrated in mega-trial of ALLHAT and proposed in guideline of JSH 2004.
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PMID:[Evidence-based usefulness of Ca antagonists and ACEIs and ARBs for the primary and secondary prevention of major cardiovascular and renal events in patients with hypertension]. 1619 17

Although it is possible to suggest that the ACE inhibitor may have a certain class effect in regards to the benefits observed in the treatment of chronic heart failure, it does not seem reasonable that the same can be assumed in the case of ARB II. Morbidity-mortality studies in chronic heart failure have only been conducted with three of the seven ARB II presently commercialized in our country. These are losartan (ELITE II), valsartan (Val-HeFT) and candesartan (CHARM). The three studies have demonstrated the utility of these drugs, although with different nuances. In these clinical comments, we review the evidence available, stressing what effects could be common to all the ARB II, such as the prevention of diabetes or atrial fibrillation and what effects may only be attributable to some of these, at least up to now. However, new information of the already finished studies and some still on-going clinical trials may help us to know the effects of the ARB II in this disease more and better.
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PMID:[ARB II in chronic heart failure. Coincidences and divergences. Class effect?]. 1623 62

Patients with signs and symptoms of heart failure and a preserved left ventricular (LV) systolic function may have significant abnormalities in diastolic function. This condition is called diastolic heart failure (DHF) and is observed in about 40% of patients with chronic heart failure (CHF). Diabetes mellitus is one of the major risk factors for DHF. Diastolic dysfunction is observed in about 40% of patients with diabetes mellitus and correlates with poor glycemic control. Suggested mechanisms for diastolic dysfunction in the diabetic heart are: (i) abnormalities in high-energy phosphate metabolism; (ii) impaired calcium transport; (iii) interstitial accumulation of advanced glycosylation end products; (iv) imbalance in collagen synthesis and degradation; (v) abnormal microvascular function, (vi) activated cardiac renin-angiotensin system; (vii) decreased adiponectin levels; and (viii) alteration in the metabolism of free fatty acids and glucose. Because most large, randomized clinical trials in CHF have enrolled only patients with systolic dysfunction, the specific management of diastolic dysfunction is largely unknown. The CHARM-Preserved (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity-Preserved) trial, the only mega trial specific for DHF (LV ejection fraction >40%), showed that the angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) candesartan cilexetil reduced hospital admissions for CHF but not cardiovascular death. Currently, the pharmacologic treatment used in systolic heart failure is also recommended in DHF and includes administration of diuretics and nitrates for pulmonary congestion, and long-term management with ACE inhibitors, ARBs, aldosterone antagonists, and beta-adrenoceptor antagonists. Poor glycemic control is associated with a high incidence of heart failure in diabetic patients, but the preferable antihyperglycemic regimen for DHF in patients with diabetes mellitus needs to be determined in further studies.
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PMID:Left ventricular diastolic dysfunction in diabetic patients: pathophysiology and therapeutic implications. 1691 23

Cardiac apelin has recently been suggested to contribute to the pathophysiology of heart failure (HF) in humans. In animal experiments, its infusion acutely improved systolic as well as diastolic LV function. Although its deficit could critically determine the cardiac dysfunction, its regulatory mechanism is unknown. Accordingly, we investigated the role and regulation of the cardiac apelin system in the diseased heart using Dahl salt-sensitive rats, which show a distinctive transition from compensatory LV hypertrophy (LVH) to HF. In the compensatory LVH stage, apelin and its receptor APJ mRNA showed no change compared with control animals, while these were markedly down-regulated in the HF stage (72% and 57% decrease, respectively). The rats were chronically treated with telmisartan (angiotensin type 1 receptor blocker [ARB], 5 mg/kg/day, n=9), ONO-4817 (matrix metalloproteinase [MMP] inhibitor, 200 mg/kg/day, n=9), bisoprolol (beta blocker, 3 mg/kg/day, n=6) or vehicle (0.5%CMC, n=9) from the LVH stage. Although the functional improvements were similar among the three treated groups 6 weeks after treatment, restoration of cardiac apelin and APJ expression was observed only in the ARB group. Furthermore, in angiotensin II-infused rats, cardiac apelin mRNA was decreased after 24 h of treatment and its restoration was achieved by treatment with ARB. These results indicate that the cardiac apelin system is markedly down-regulated in experimental HF and may be regulated by the angiotensin II-angiotensin type 1 receptor system directly. Inhibition of the renin-angiotensin system may have beneficial effects, at least in part, through restoration of the cardiac apelin system in the treatment of HF.
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PMID:Down-regulation of cardiac apelin system in hypertrophied and failing hearts: Possible role of angiotensin II-angiotensin type 1 receptor system. 1700 96

Unlike heart failure with a low ejection fraction, there is no evidence-based treatment for heart failure with preserved ejection fraction which improves clinical outcomes. Indeed, the only evidence for any treatment effect comes from small studies with verapamil where this drug increased exercise capacity and reduced a heart failure score. Large trials are presently underway which are examining the effect of treatment with an ACE inhibitor, ARB and aldosterone antagonist in patients with heart failure and preserved ejection fraction.
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PMID:The treatment of heart failure with preserved ejection fraction ("diastolic heart failure"). 1693 33


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