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

Various configurations of conditioned skeletal muscle are under investigation for cardiac assistance in patients with end-stage cardiac failure. Optimal timing of conditioned skeletal muscle contraction is essential for effective cardiac augmentation. However, unlike mechanical methods of assistance, skeletal muscle requires time to develop peak tension. We measured "time to 50% peak tension" and "time to 90% peak tension" using an electrical strain gauge in 12 canine latissimus dorsi muscles (6 untrained controls and 6 trained with 3 months of electrical stimulation at 25 Hz with a 15% duty cycle). The "time to 50% relaxation" and the "time to 90% relaxation" after discontinuation of the stimulus were also measured. Conditioned skeletal muscle required significantly more time to develop peak tension than unconditioned skeletal muscle. Relaxation was also significantly prolonged in conditioned muscle. Notably, conditioned lattisimus needed, on average, 0.35 sec to develop peak tension and 0.20 sec for 90% relaxation. Thus, 0.55 sec of each muscle contraction/relaxation cycle was devoted to development of peak tension and subsequent relaxation. At normal canine heart rates of approximately 120 beats per minute (0.50 sec per cardiac cycle), conditioned skeletal muscle may take up to 70% of each cardiac cycle (0.35 sec) to develop 90% of peak tension. The recognition of this phenomenon in conditioned skeletal muscle is important for effective contraction timing of both human and animal skeletal muscle assist devices. Development of proper conditioning regimens for such devices may benefit from identification of those training parameters which produce a minimal "time to peak tension."
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PMID:Latency of skeletal muscle contraction after pulse train stimulation: an important factor in correct timing of skeletal muscle cardiac assist devices. 799 44

Exertional intolerance is a major clinical problem in ambulatory patients with chronic heart failure and is associated with both muscle fatigue and dyspnea. The increased muscle fatigability is most likely caused by a combination of muscle underperfusion and muscle deconditioning; patients frequently exhibit skeletal muscle atrophy, altered muscle metabolism and reduced mitochondrial-based enzyme levels, consistent with deconditioning. The muscle underperfusion is largely due to impaired arteriolar vasodilation within exercising muscle. Exertional dyspnea appears to be due to increased respiratory muscle work mediated by excessive ventilation and decreased lung compliance. Both excessive carbon dioxide production, secondary to increased muscle lactate release, and increased lung dead space contribute to the excessive ventilation. Decreased lung compliance is caused by chronic pulmonary congestion and fibrosis. Optimal management of exercise intolerance in patients with heart failure requires an understanding of the role of these multiple potential contributors to exertional fatigue and dyspnea.
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PMID:Factors contributing to the exercise limitation of heart failure. 837 1

Optimal ventriculoarterial coupling, in terms of maximal energetic efficiency, was recently analyzed by analytic and experimental studies. Whereas for normal hearts the analytic predictions agreed well with measured data, failing hearts were found to operate remote from the predicted optimal conditions. An analysis of optimal coupling is developed in the present study, based on constrained optimization. The constraints are based on the concept that the system must comply with physiological requirements (restrictions) under all conditions. Optimization using the mean pressure as a constraint yielded results similar to the unconstrained case in the normal heart but different with the failing heart: in the failing heart the optimal arterial elastance was found to be larger than the ventricular elastance, whereas the opposite was predicted by the unconstrained optimization. If an additional constraint on the end-systolic pressure is used, a unique solution of the coupling state is obtained. The predicted coupling ratio was found to match published data from normal subjects and heart failure patients, where in the latter group it was found to be remote from the optimal efficiency state. An increase in ventricular contractility and reduction in afterload were shown to shift the nonoptimal coupling state toward the optimal one. This prediction complies with the use of inotropic agents and vasodilators as the mainstay of heart failure treatment. This study may provide a convenient framework of analysis for the assessment of the ventriculoarterial coupling and for the evaluation of the cardiovascular effects of specific drug treatments.
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PMID:Constrained optimization of ventricular efficiency in normal and failing hearts. 847 5

The treatment of congestive heart failure has seen considerable changes: while treatment with diuretics, digitalis glycosides and vasodilators has remained the mainstay of therapy, recently neurohumeral inhibition has been developed as an important principle: ACE-inhibitors have been shown to significantly improve quality of life and exercise performance and to substantially reduce mortality. Beta-blockers have been employed with increasing success mainly in congestive heart failure due to dilated idiopathic cardiomyopathy, in which a significant improvement in symptoms and life expectancy has been demonstrated. However, the precise mechanisms by which beta-blockade improves congestive heart failure remain to be elucidated. In addition to direct sympathoadrenal inhibition, reduction of heart rate may also play a major role in the therapeutic efficacy of beta-blockade in congestive heart failure. In the normal human heart increase in heart rate is accompanied by an increase in myocardial contractile performance (Bowditch-Treppe phenomenon). In chronic heart failure the myocardium undergoes a phenotype change which includes alterations of the activity of enzymes regulating calcium homoeostasis. The sarcoplasmic reticulum calcium ATPase (SERCA) is depressed both in function, as well as in expression. At the same time the sarcolemmal sodium-calcium exchanger is increased both in function and in expression. The result is a characteristic change in calcium homoeostasis with decreased diastolic uptake of calcium into the sarcoplasmic reticulum with subsequently reduced calcium release during the next systole, resulting in reduced contractile performance. At the same time increased capacity of the sodium-calcium exchanger extrudes intracellular calcium ions to the extra-cellular space, thereby rendering these ions unavailable for the contractile cycle. A result of these, seemingly specific, phenotype changes is an alteration of the force/frequency relationship. Instead of increasing force of contraction with increasing heart rates, in the chronically failing myocardium the contractile performance declines with increasing heart rates and only improves with decreasing rates. Optimal performance can be seen at heart rates as low as 30 beats.min. Studies employing photoluminescence markers of free cytosolic calcium, such as aequorin, have shown that there is a direct correlation between free cytosolic calcium and contractile performance at different levels of heart rate. It is likely, therefore, that the heart rate reduction with beta-blockade may provide the major explanation for the therapeutic benefits of beta-blockade in chronic congestive heart failure.
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PMID:Pathophysiological targets for beta-blocker therapy in congestive heart failure. 873 64

Congestive heart failure is a major public health problem in developed countries. There have been significant advances in the management of this condition over the last few decades. However, many patients are still not receiving adequate therapy. Optimal management requires appropriate investigation, education, counselling, medical treatment and planned follow-up. This review outlines the recommended approach for optimal management of patients with heart failure.
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PMID:Current management of congestive heart failure. 873 27

Treatment of heart failure attempts to reduce symptoms, increase functional capacity and prolong survival. Optimal therapy usually requires a combination of several drugs. At present, ACE inhibitors are the drugs of first choice, but must be combined with diuretics in symptomatic patients. Digitalis glycosides are still an important supplement to diuretics and ACE inhibitors. Specific angiotensin receptor antagonists such as losartan have an effect comparable with that of ACE inhibitors and may possess certain advantages because of their direct effect at the receptor level. Extensive research has been conducted in the treatment of heart failure. Newer direct acting vasodilators such as flosequinan and epoprostenol have demonstrated improved exercise tolerance but have an adverse effect on mortality. Positive inotropic agents consisting of a heterogeneous group of drugs have been evaluated. Although novel agents such as xamoterol, milrinone, pimobendan and vesnarinone have demonstrated improved haemodynamics and improved symptoms, they are not advisable at present due to increased mortality related to treatment or a high incidence of adverse events. beta-Blockers, used judiciously, may improve functional capacity as well as mortality and may be an important supplement to current conventional treatment. The new generation of beta-blockers with vasodilating properties such as carvedilol and bucindolol appear promising.
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PMID:Novel drugs and current therapeutic approaches in the treatment of heart failure. 888 74

Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.
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PMID:What, if anything, is controversial about calcium antagonists? 896 30

The prognostic value of thrombolytics, aspirin, beta-blockers and ACE-inhibitors has been well documented in large clinical trials, but the application of these drugs in clinical practice is not known. MITRA is a multicenter study of 54 hospitals in a defined region in southwest Germany. The aim is to document actual clinical practice (pilot phase) and to establish an individually optimised prognostic therapy for acute myocardial infarction, considering only the absolute contraindications for each drug. In the pilot phase, 1303 consecutive patients with acute transmural myocardial infarction were enrolled. The median age was 66 years, the prehospital time was 2.7 hours. 47% had an anterior infarction. In the subgroup of patients without absolute contraindications, only 53.4% were treated with thrombolytics, 87.6% with aspirin, 37.1% with beta-blocker, and 17.4% with ACE-inhibitor. Out of these, patients were classified as "optimally treated" if they received thrombolysis, aspirin as well as beta-blocker. Patients were also included if any of these medications was withheld in the presence of absolute contraindications. Treatment was defined suboptimal, if the patients did not receive any of these three medications despite the absence of absolute contraindications. Only 29% (n = 383) received an optimal post-infarction therapy and 71% (n = 775) a suboptimal treatment. The univariate analysis revealed 10 variables influencing optimal therapy. In this subgroup patients were younger, they more often had clear ECG-findings or left bundle branch block, an anterior infarction, acute cardiac failure, AV-block, bradycardia, recent trauma or surgery (less then 2 weeks) and a severe chronic obstructive lung disease. The prehospital time was more often available. Early mortality after 2 days was 5.0% versus 9.3% in the suboptimal treated patients (OR: 0.5, CI: 0.30-0.86) the total inhospital mortality was 10.9% in the optimal versus 17.7% in the suboptimal group (OR: 0.6, CI: 0.38-0.84). In a multivariate analysis the parameter "optimal treatment" was found to be an independent predictor of the early (OR = 0.4; CI: 0.20-0.69) and the inhospital mortality (OR = 0.4; CI: 0.25-0.64). The following in-hospital events occurred: stroke 2.8%, reinfarction 12.9%, cardiac failure 21.5%, cardiogenic shock 10.4% and in-hospital mortality 18.1% (2-days mortality 9.5%). Pharmacological therapy for acute myocardial infarction is inconsistent with the recommendations suggested in recent clinical trials and needs to be individually optimised. Optimal treatment is an independent predictor of early and inhospital mortality.
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PMID:[Early treatment of acute myocardial infarct: implementation of therapy guidelines in routine clinical practice, MITRA pilot phase]. 923 99

The differentiation between systolic and diastolic CHF is clinically important because it allows one to formulate an appropriate therapeutic regimen. As a rule, ACE inhibitors have become a major component in the treatment of systolic heart failure; diuretics, digoxin, and other vasodilators are used in conjunction with them. Optimal therapy for diastolic heart failure remains to be defined. Further research is required for this subset of patients. Numerous other support measures, such as counseling, activity, diet, patient knowledge of medications, and compliance, all affect the patient's outcome.
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PMID:Congestive heart failure. 961 66

The importance of cardiovascular system involvement in hyperthyroidism has been recognized for many years. In the elderly patient, often with mild but prolonged elevation of plasma thyroid hormones, symptoms and signs of heart failure and complicating atrial fibrillation (AF) may dominate the clinical picture and mask the more classic endocrine manifestations of the disease. Impaired cardiopulmonary function and exercise capacity, significantly more marked in older patients, is observed in hyperthyroidism. Thyrotoxicosis can aggravate pre-existing heart disease and can also lead to AF, congestive heart failure, or worsening of angina pectoris. Regarding the high incidence of AF in older patients with hyperthyroidism, it is also important to detect subclinical hyperthyroidism in older patients with AF, thus warranting the measurement of the serum thyrotropin (TSH) concentration for early recognition and treatment. Most cardiac abnormalities return to normal once a euthyroid state has been achieved, although AF may persist in a minority. Optimal treatment requires rapid and definitive antithyroid therapy. Furthermore, anticoagulation is recommended for thyrotoxic patients with AF older than 50 years, those who have histories of previous emboli, hypertension, or with echocardiographic evidence of left atrial enlargement and/or myxomatous valves.
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PMID:Cardiac risks of hyperthyroidism in the elderly. 992 Mar 73


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