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

Calcium antagonists have multiple mechanisms whereby they are able to protect against myocardial ischaemia. Recently questions have been posed about the long-term safety of this group of agents. This article is a selective rather than a complete review of the problems. Fears have largely centred around rapidly acting nifedipine when inappropriately used. This agent remains useful in Prinzmetal's angina, a condition in which there are no long-term comparative outcome studies. Current evidence is that verapamil is as safe and as effective as the beta-blocker in effort angina and that non-dihydropyridines (verapamil and diltiazem) are efficacious in the follow up of non-Q wave infarct. Verapamil post-infarct is safe and reduces reinfarction, provided that clinical heart failure is first excluded.
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PMID:Mechanisms whereby calcium channel antagonists may protect patients with coronary artery disease. 904 44

We sought to characterize the effects of the nonselective Ca2+ channel antagonist, verapamil, and the vascular-selective Ca2+ channel antagonist, felodipine, on obese, hypertensive, heart failure-prone, female SHHF/Mcc-fa(cp) rats. Rats were treated for < or = 2 months with verapamil (57 mg/kg/day) or felodipine (24 mg/kg/day). Blood pressures were determined at monthly intervals by the tail-cuff method. Heart weights and myosin isoforms were measured at the end of treatment. Direct cardiac effects of verapamil and felodipine were examined in electrically field stimulated, fura-2/AM-loaded cardiomyocytes. Both Ca2+ channel antagonists reduced systolic blood pressures. Verapamil, but not felodipine, increased heart weights and decreased expression of the myosin V1 isoform. In older animals, 75% of those treated with verapamil developed end-stage congestive heart failure. Age-matched control and felodipine-treated rats remained healthy. In isolated cardiomyocytes, 10(-9) M verapamil significantly reduced Ca2+ transient amplitudes but 10(-9) M felodipine did not. Both Ca2+ channel antagonists reduced blood pressures in obese, hypertensive, female SHHF rats. Verapamil, but not felodipine, produced heart failure in a large number of these animals. Differences between the in vivo effects of the two Ca2+ channel antagonists may be related to the differing effects on sarcolemmal Ca2+ influx.
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PMID:Verapamil accelerates the transition to heart failure in obese, hypertensive, female SHHF/Mcc-fa(cp) rats. 923 52

Recently, there has been some controversy concerning calcium antagonists, suggesting the need for further debate on this heterogeneous class of drugs. Three chemical families, dihydropyridines (DHP), phenylalkylamines (verapamil) and benzothiazepines (diltiazem) bind to the type L receptors of the calcium channels with different binding, modulation and tissue selectivity characteristics. DHP are selective for type L receptors and block the extracellular portion of the channel leading to vigorous vasodilatation and little or no cardiodepressive effect. Diltiazem and verapamil also interfere with type T channel receptors. These drugs have a cardiodepressive and a bradycardia effect. Verapamil blocks the intracellular portion of the calcium channel at the site where part of the catecholamine effect occurs, leading to less reflex sympathetic activation than with other calcium antagonists (namely DHP). Deleterious sympathetic stimulation is proportional to the intensity and degree of rapid onset of arterial vasodilatation and is attenuated with slow-release formulations. Calcium antagonists in general have an anti-angina effect but high-dose short-acting DHP can cause excessive vasodilatator leading to subsequent ischemia. In chronic stable angina, slow-release verapamil has been shown to have a preventive clinical effect comparable to that of beta blockers. Slow-release nifedipine is effective and safe but must be associated with betablockers. In unstable angina, only those calcium antagonists with a bradycardia effect appear to have an effect similar to beta blockers. Beta blockers are nevertheless to be preferred in these patients (excepting Prinzmetal angina) until results of convincing clinical studies are available. After the initial phase of myocardial infarction, again only calcium antagonists with a bradycardia effect have been shown to have a beneficial effect, in patients without cardiac failure: diltiazem in infarction without Q-wave and verapamil in all infarctions, in case of residual ischemia to reduce the risk of recurrence.
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PMID:[Calcium antagonists in ischemic heart disease]. 941 Oct 6

ACTIONS OF THE SYMPATHETIC NERVOUS SYSTEM: The sympathetic nervous system is an important cardiovascular regulator, particularly during stress and exercise; its sympathetic nervous activity is regulated in centers in the brain stem and transmitted to organs and blood vessels that are innervated by sympathetic nerve endings. In the heart, the sympathetic nervous system increases heart rate and contractility. The effect of the sympathetic nervous system in different vascular beds depends on the degree of innervation, the distribution of postjunctional receptors and the effect of local mediators. Overactivation of the sympathetic nervous system may lead to hypertension and is involved in heart failure. The degree of sympathetic activation determines prognosis in heart failure. Hence, vasodilators ideally should also blunt sympathetic activity, or at least avoid activating it. DIFFERENCES AMONG CALCIUM ANTAGONISTS: Calcium antagonists are widely used for the treatment of hypertension and coronary artery disease. Their main mechanism of action is inhibition of L-type Ca2+ channels. Short-acting nifedipine leads to a marked increase in heart rate, sympathetic nerve activity and plasma catecholamines, similar to those induced by a cold pressor test. With long-acting nifedipine heart rate does not increase, but sympathetic nerve activity does increase. Other calcium antagonists have been less thoroughly investigated, but indirect evidence suggests differences between the different classes. Verapamil and diltiazem lower heart rate. Plasma noradrenalin measurements suggest that verapamil does not stimulate the sympathetic nervous system, but tends to suppress it. Second-generation dihydropyridines with longer duration of action do not increase heart rate; their effects on peripheral sympathetic nerve activity are not clear. Thus, in summary, the different classes of calcium antagonists differ with regard to their effects on sympathetic nerve activation. A decrease in heart rate and nerve activity might be beneficial for long-term prognosis, particularly in hypertension and heart failure.
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PMID:Calcium antagonists and sympathetic nerve activation: are there differences between classes? 953 92

CLINICAL TRIALS WITH VERAPAMIL AND TRANDOLAPRIL: In the Danish Verapamil Infarction Trial II, verapamil improved survival in patients without heart failure but had no effect in patients with heart failure who were receiving diuretic treatment. In the Acute Infarction Ramipril Efficacy study ramipril improved survival in patients receiving diuretic treatment but had no effect in patients not receiving diuretics. COMBINATION WITH THERAPY WITH VERAPAMIL AND TRANDOLAPRIL: By combining verapamil with trandolapril we hypothesized that we could obtain an improvement in left ventricular function and prevent cardiac events. In an open study of 14 patients with angina pectoris and left ventricular ejection fraction below 40%, treatment with trandolapril-verapamil significantly improved left ventricular function. In a double-blind randomized study of 100 postinfarct patients with congestive heart failure the cardiac event rate was significantly lower in verapamil-trandolapril-treated than in the trandolapril-treated patients. These results indicate that the combined treatment with verapamil and trandolapril might be beneficial in patients with ischaemic heart disease and congestive heart failure.
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PMID:Congestive heart failure and ischaemic heart disease treated with trandolapril and verapamil. DAVIT Study Group. Danish Verapamil Infarction Trial. 953 1

Verapamil is well tolerated in patients with stable and unstable angina pectoris, as well as in patients with threatened infarction. No data exist documenting verapamil to be inferior to beta-blockers in these stages of coronary heart diseases. In the prethrombolytic era i.v. intervention with verapamil did not add any benefit in the early phase of AMI. However, a retrospective analysis suggests the hypothesis that i.v. verapamil given in combination with thrombolysis may improve the prognosis, and an ongoing study (VAMI trial) examines this hypothesis. When given in the late in-hospital phase of AMI to patients without heart failure verapamil significantly reduces mortality and morbidity. When given in the late in-hospital phase to patients with heart failure verapamil did not cause the course or prognosis to deteriorate and might even improve it in patients with residual ischaemia, especially when given in combination with an ACE-inhibitors. A planned study (DAVIT III study) has to confirm these preliminary data.
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PMID:Verapamil in acute myocardial infarction. The rationales of the VAMI and DAVIT III trials. 1075 9

Verapamil is well tolerated in patients with stable and unstable angina pectoris, as well as in patients with threatened infarction. No data exist documenting verapamil to be inferior to beta-blockers in these stages of coronary heart diseases. In the pre-thrombolytic era i.v. intervention with verapamil did not add any benefit in the early phase of AMI. However, a retrospective analysis suggests the hypothesis that i.v. verapamil given in combination with thrombolysis may improve the prognosis, and an ongoing study (VAMI trial) examines this hypothesis. When given in the late in-hospital phase of AMI to patients without heart failure verapamil significantly reduces mortality and morbidity. When given in the late in-hospital phase to patients with heart failure verapamil did not cause the course or prognosis to deteriorate and might even improve it in patients with residual ischaemia, especially when given in combination with an ACE-inhibitors. A planned study (DAVIT III study) has to confirm these preliminary data.
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PMID:Verapamil in acute myocardial infarction. The rationales of the VAMI and DAVIT III trials. 1051 65

The risk of interference with anaesthesia and the risk of decompensation of the disease must be considered for each drug. Beta-blockers reduce the body's capacity to react to hypovolaemia, but they are beneficial by limiting the response to nociceptive stimuli and by reducing the incidence of myocardial ischaemia. Treatment should therefore be continued. Interferences with the dihydropyridine class of calcium channel blockers on peripheral vasomotor activity are moderate and additive. These agents are well tolerated and can be continued until the operation. Verapamil and diltiazem have a chronotropic and negative inotropic effect which is additive with that of anaesthetics. Administration of these drugs before the operation does not raise any major problems, nor does their discontinuation. Angiotensin-converting enzyme (ACE) inhibitors, used in hypertension and heart failure, considerably reduce the tolerance of factors modifying the blood pressure equilibrium, especially hypovolaemia or haemorrhage. In practice, ACE inhibitors carry a risk of intraoperative hypotension, requiring the use of vasopressor amines to maintain blood pressure. Continuation of treatment has only minimal advantages, regardless of the indication and there is no risk of rebound effect after stopping treatment. The treatment washout period depends on the duration of action of the product. However, discontinuation of treatment is never imperative, regardless of the context.
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PMID:[How to handle cardiovascular treatments during general anesthesia?]. 1255 68

This paper reviews the current literature pertaining to calcium channel blockers, including their classification, properties, and therapeutic indications, in light of several recent trials that have addressed their safety. Calcium channel blockers are a structurally and functionally heterogeneous group of medications that are used widely to control blood pressure and manage symptoms of angina. They are classified as dihydropyridines or nondihydropyridines. As a class, they are well tolerated and are associated with few side effects. The question of whether they may precipitate cardiovascular events has been largely settled by recent trials, such as the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the International Verapamil Slow-Release/Trandolapril Study (INVEST), and the Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) study, in which no such association was found. Even so, the use of these agents has been linked with an increased risk of heart failure. Thus, long-acting calcium channel blockers may be safely used in the management of hypertension and angina. However, as a class, they are not as protective as other antihypertensive agents against heart failure.
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PMID:Calcium channel blockers: an update. 1470 64

Physicians treating hypertrophic cardiomyopathy (HCM) are faced with unique management challenges. Understanding pathophysiology and overall good prognosis forms the basis for medical treatment. Treatment is tailored by the presence or absence of outflow tract gradient and individual symptoms. In all patients, formal stratification for sudden death risk is necessary, with consideration of defibrillator implantation in patients deemed to be at high risk. In patients with no or only mild symptoms the approach of watchful waiting is often appropriate. For symptomatic patients with non-obstructed disease medical treatment with calcium channel blockers and beta-blockers is aimed to improve heart failure symptoms, and ischemia. Verapamil is the most often used, with likely benefit of relieving ischemia. Obstruction, most commonly due to systolic anterior motion of the mitral valve (SAM) and mitral-septal contact, occurs in >/=50% of all HCM patients, worsening symptoms and increasing mortality. Successful medical treatment of obstruction with negative inotropes slows acceleration of left ventricular ejection with delay in SAM, ultimately yielding a lower pressure gradient. Beta -blockers are the first line treatment in obstructive HCM predominantly by mitigating provocable gradients. The magnitude of symptom relief with verapamil is similar to the effect of beta -blockade. Disopyramide combined with beta -blockade is thought by some to be the most effective medical treatment of obstruction, and has been shown to be safe and not pro-arrhythmic. Most symptomatic HCM patients with significant obstruction at rest or provocation can be successfully managed with long-term medication alone.
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PMID:Pathophysiology of hypertrophic cardiomyopathy determines its medical treatment. 1716 64


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