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PubMed1994

Amlodipine: a new calcium antagonist.

The chemistry, pharmacology, pharmacokinetics, efficacy, and adverse effects of amlodipine are reviewed. Amlodipine belongs to the dihydropyridine subclass of calcium antagonists. Amlodipine is a potent peripheral and coronary vasodilator with high selectivity for vascular smooth muscle and minimal effect on myocardial contractility or cardiac conduction. Absorption after oral administration is slow, and the duration of action is long, with a half-life of 36-45 hours. Amlodipine has FDA-approved labeling for use in the treatment of hypertension, chronic stable angina, and vasospastic angina. The agent is also indicated for use in hypertensive or anginal patients who also have congestive heart failure due to systolic dysfunction (New York Heart Association classes II and III). Clinical trials suggest that effective 24-hour control of hypertension and angina is provided by once-daily administration of amlodipine 5-10 mg alone or in combination with other drugs. No clinically important drug interactions have been observed to date. Amlodipine has not shown any unfavorable effects on serum glucose or lipid levels. The most common adverse effect is peripheral edema. Amlodipine is effective and well tolerated when given alone or in combination with other drugs for the treatment of hypertension and angina. Amlodipine may offer advantages over verapamil, diltiazem, and nifedipine in patients with hypertension or angina with associated congestive heart failure due to systolic dysfunction.

Amlodipine↗
PubMed2005

Peripartum cardiomyopathy.

OBJECTIVE: To provide a review of the cardiac and obstetrical literature regarding the development of peripartum cardiomyopathy and, in particular, to examine risk factors, incidence, diagnosis, prognosis, and evidence-based treatment modalities. DESIGN: An extensive review of the current literature. RESULTS: Peripartum cardiomyopathy is a cardiomyopathy of unknown cause that occurs in pregnant females, most commonly in the early postpartum period. It shares many clinical characteristics with idiopathic dilated cardiomyopathy but occurs at a younger age and is associated with a better prognosis. Diagnosis is based upon the clinical presentation of congestive heart failure and objective evidence of left ventricular systolic dysfunction. Conventional pharmacologic therapy for congestive heart failure, such as diuretics, digoxin, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and beta-adrenergic blockers, are routinely used and are quite effective. For those patients who remain refractory to conventional pharmacologic therapy, cardiac transplantation and mechanical circulatory support are viable options. CONCLUSION: Mortality rates in peripartum cardiomyopathy have decreased, and this is most likely related to advances over the past 5 yrs in medical therapy for heart failure. Aggressive use of implantable defibrillators has significantly reduced the risk of sudden death in these patients. For >50% of peripartum cardiomyopathy patients, left ventricular function normalizes with pharmacologic therapy. However, subsequent pregnancies almost always are associated with recurrence of left ventricular systolic dysfunction.

Cardiomyopathies↗
PubMed2003

Reappraisal of beta-blocker therapy in the acute and chronic post-myocardial infarction period.

In patients presenting with acute myocardial infarction (MI), the early use of intravenous beta-blockade followed by short-term oral administration in the absence of reperfusion therapy has shown a modest reduction in mortality. In contrast, major reductions in mortality and reinfarction have been shown when beta-blockers have been used soon after an acute MI and continued long-term. These benefits were observed in trials conducted in the 1970s and 1980s, prior to the widespread use of reperfusion therapies, antiplatelet agents, and angiotensin-converting enzyme inhibitors; those trials excluded patients with postischemic heart failure. Recently, the CAPRICORN trial has shown a significant reduction in all-cause mortality and reinfarction in post-MI patients with systolic dysfunction, in response to carvedilol. In spite of compelling evidence supporting the use of beta-blockers in the post-MI setting, data published by the National Cooperative Cardiovascular Project have shown that fewer than half of all post-MI patients receive beta-blockers as long-term therapy. It appears that post-MI patients with perceived contraindications, such as advanced age, diabetes, heart failure, peripheral vascular disease, and/or chronic pulmonary obstructive disease, may derive a substantial benefit from the use of beta-blockers. Given the considerable evidence from randomized clinical trials, the use of beta-blockers is recommended in all post-MI patients without a contraindication, particularly in those with left ventricular systolic dysfunction.

Acute Disease↗
PubMed2004

A description of the clinical characteristics at baseline of patients recruited into the Carvedilol or Metoprolol European Trial (COMET).

BACKGROUND & AIMS: The COMET trial was a prospective, double-blind, randomised trial comparing carvedilol, a comprehensive adrenergic receptor antagonist, with metoprolol, a beta-1-selective agent in patients with heart failure and left ventricular systolic dysfunction. The trial showed a reduction in mortality with carvedilol that was consistent across subgroups. The purpose of this report is to describe in greater detail the heterogeneity of this population at baseline with particular reference to the impact of symptomatic severity, age and gender on patient characteristics. METHODS: A descriptive report using data entered in the COMET study data-base. RESULTS: The characteristics of the population studied were similar to those reported in previous trials of beta-blockers. Almost all patients were receiving diuretics and ACE inhibitors with few patients taking angiotensin receptor blockers. As expected, older patients had more co-morbidity. Older patients and women reported worse symptoms and poorer well-being despite similar ventricular dimensions and systolic dysfunction. NT-proBNP was higher in patients with more severe symptoms and older patients but not in women, although differences in NT-proBNP may have been confounded by differences in renal function. CONCLUSION: Age and gender, as well as the severity of cardiac dysfunction, appear to have an important effect on the severity of heart failure symptoms and patient 'well-being'. This could have important implications for the relationship between symptoms and prognosis and therefore the way in which patients are selected for clinical trials and the goals of treatment. This will be the subject of further analyses.

Adrenergic beta-Antagonists↗
PubMed2004

Accuracy and pitfalls of early diastolic motion of the mitral annulus for diagnosing constrictive pericarditis by tissue Doppler imaging.

Mitral annular velocities are reportedly useful in diagnosing constrictive pericarditis (CP); however, their exact efficacy in larger clinical settings remains unevaluated. This study reexamined the role of longitudinal tissue Doppler imaging in diagnosing CP in clinical practice. Tissue velocity imaging (GE Vingmed System Five) was performed in 122 subjects (87 referred with clinically suspected CP and 35 age- and sex-matched controls). Of the 87 subjects with suspected CP, 45 (51.7%) had CP confirmed at surgery, 11 (12.6%) had restrictive heart disease, 20 (23.0%) had right heart failure due to cor pulmonale, and the other 11 (12.6%) had old pericardial effusions and no hemodynamic evidence of constriction on follow-up echocardiography. Of the 45 patients with CP, mitral early diastolic (Ea) annular velocities from septal and lateral regions were normal (>/=8 cm/s) in 40 (88.9%) and decreased (<8 cm/s) in 1 or both regions in 5 (3 with left ventricular systolic dysfunction, 2 with extensive mitral annular calcification). Of 11 patients with restrictive cardiomyopathy, 8 (72.7%) had reduced Ea (<8 cm/s) and 3 showed normal Ea velocity in 1 or both corners of the mitral annulus. All except 2 patients with right-sided heart failure from cor pulmonale and those with previous pericardial effusion had normal Ea velocities. A normal Ea velocity improved recognition of CP, particularly in the presence of nondiagnostic 2-dimensional or transmitral flow-Doppler imaging. The overall sensitivity and specificity for diagnosing CP using tissue Doppler incrementally with M-mode, 2-dimensional, and transmitral flow Doppler were 88.8% and 94.8%, respectively. Mitral annular velocities help with diagnosis and differentiation of CP in most cases, except in the presence of extensive annular calcification, left ventricular systolic dysfunction, or segmental nonuniformity in myocardial velocities.

Adult↗
PubMed2006

Diagnostic and therapeutic challenges in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure.

Chronic obstructive pulmonary disease (COPD) and heart failure (CHF) are common conditions. The prevalence of COPD ranges from 20% to 30% in patients with CHF. The diagnosis of CHF can remain unsuspected in patients with COPD, because shortness of breath is attributed to COPD. Measurement of plasma B-type natriuretic peptide (BNP) levels helps to uncover unsuspected CHF in patients with COPD and clinical deterioration. Noninvasive assessment of cardiac function may be preferable to BNP to uncover unsuspected left ventricular (LV) systolic dysfunction in patients with stable COPD. Patients with COPD or CHF develop skeletal muscle alterations that are strikingly similar. Functional intolerance correlates with severity of skeletal muscle alterations but not with severity of pulmonary or cardiac impairment in COPD and CHF, respectively. Improvement of pulmonary or cardiac function does not translate into relief of functional intolerance in patients with COPD or CHF unless skeletal muscle alterations concomitantly regress. The mechanisms responsible for skeletal muscle alterations are incompletely understood in COPD and in CHF. Disuse and low-level systemic inflammation leading to protein synthesis/degradation imbalance are likely to contribute. The presence of COPD impacts on the treatment of CHF, as COPD is still viewed as a contraindication to beta-blockade. Therefore, COPD often deprives patients with CHF due to LV systolic dysfunction of the most beneficial pharmacologic intervention. A large body of data indicates that patients with COPD tolerate well selective beta-blockade that should not be denied to CHF patients with concomitant COPD.

Adrenergic Antagonists↗
PubMedDate not supplied

Angiotensin II receptor blockers in the treatment of heart failure.

Heart failure treatment centers on antagonism of the renin-angiotensin-aldosterone system and adrenergic nervous system. Angiotensin-converting enzyme (ACE) inhibitors have been shown to benefit patients with left ventricular systolic dysfunction irrespective of symptoms. Despite ACE inhibitor use, left ventricular dysfunction continues to progress in most patients. In addition, ACE inhibitors are substantially underused in patients who would benefit, in large part due to physician concern over potential adverse effects. Angiotensin receptor blockers (ARBs) have been proposed as either potential substitutes for ACE inhibitors or as additive therapy for heart failure patients. The authors will review the importance of the renin-angiotensin-aldosterone system in the progression of heart failure, as well as the mechanisms by which ACE inhibitors and ARBs counteract this effect. The clinical evidence to date supporting the use of ARBs in heart failure also will be reviewed. Based on current trials, ARBs are suitable substitutes for ACE inhibitors in patients who have true ACE inhibitor intolerance, but ACE inhibitors should still be considered first-line therapy in the treatment of left ventricular systolic dysfunction and heart failure. ARBs are a reasonable additive therapy in patients on maximal ACE inhibitor therapy who remain symptomatic, especially in patients unable to tolerate beta blockade.

Angiotensin II↗
PubMed2006

Outcome of patients with low ejection fraction undergoing coronary artery bypass grafting: renal function and mortality after 3.8 years.

BACKGROUND: There are few data regarding medium-term outcome of coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) systolic dysfunction, particularly in the modern era, and even less assessing preoperative factors that might identify patients at highest risk. METHODS AND RESULTS: Three hundred seventy-nine consecutive patients with LV ejection fraction < or = 35%, who underwent isolated first CABG between 1995 and 1999 were studied. Potential preoperative and perioperative predictors of outcome were recorded and patients followed-up for a median of 3.8 years. The primary study end-point was all-cause mortality. The 30-day, 1-year, and 3-year survival rates were 94.5%, 88%, and 81%, respectively. The independent predictors of mortality were preoperative estimated glomerular filtration rate (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97 to 0.99 per mL/min/1.73 m2; P<0.001) and age (HR, 1.03; 95% CI, 1.01 to 1.06 per year; P=0.005). CONCLUSIONS: Patients with significant LV systolic dysfunction undergoing isolated CABG using contemporary techniques have a good medium-term survival. Renal dysfunction is the strongest independent predictor of mortality.

Aged↗
PubMed2002

Interaction between aspirin and angiotensin-converting enzyme inhibitors: should they be used together in older adults with heart failure?

PURPOSE: To determine whether the prostacyclin-inhibiting properties of aspirin counteracts the bradykinin-induced prostacyclin-stimulating effects of angiotensin-converting enzyme (ACE) inhibitors, thereby attenuating the beneficial effects of ACE inhibitors in heart failure patients. BACKGROUND: Most heart failure patients are older adults. Heart failure is the number one hospital discharge diagnosis of older Americans. The renin-angiotensin system plays a major role in the pathophysiology of heart failure, and ACE inhibitors play a pivotal role in the management of heart failure. Large-scale double-blind randomized trials have demonstrated the survival benefits of using ACE inhibitors in patients with heart failure associated with left ventricular systolic dysfunction. In addition to inhibiting the conversion of angiotensin I to angiotensin II, ACE inhibitors also decrease the breakdown of bradykinin. Bradykinin, a potent vasodilator, acts by stimulating formation of vasodilatory prostaglandins such as prostacyclin, whereas aspirin or acetyl salicylic acid inhibits the enzyme cyclooxygenase, which in turn decreases the production of the prostaglandins. Coronary artery disease and hypertension are the two major underlying causes of heart failure. Most heart failure patients are also on aspirin. There is evidence that aspirin at a daily dose of 80 to 100 mg prevents the synthesis of thromboxane A2 by platelets while relatively sparing the synthesis of prostacyclin in the vascular endothelium. Aspirin at a daily dose of 325 mg has significant inhibitory effects on the vasodilatory prostacyclin synthesis. Studies have demonstrated that, in heart failure patients, low-dose aspirin has no adverse effect on hemodynamic, neurohumoral, or renal functions. Whether the prostacyclin-inhibiting effects of aspirin attenuate some of the beneficial effects of ACE inhibitors mediated by prostacyclin stimulation in heart failure patients is currently unknown. METHODS: Data from large clinical trials investigating the interaction between aspirin and ACE inhibitors were analyzed to determine the effect of aspirin on the vasodilatory actions of ACE inhibitors in heart failure patients, and the results were analyzed on the basis of theoretical and laboratory findings. The studies included are the Studies of Left Ventricular Dysfunction (SOLVD) (N=6,797), the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) (N=6,090), the Captopril and Thrombolysis Study (CATS) (N=296), and another study involving 317 subjects. The data from these clinical trials investigating the interaction between aspirin and ACE inhibitors included 13,470 subjects. Most of the subjects received aspirin. In the SOLVD study, subjects received aspirin or dipyridamole. Subjects were followed up for an average of about 6 years. RESULTS: In the SOLVD study, subjects were followed up for 41.1 months in the treatment trial and 37.4 months in the prevention trial. Patients who received aspirin or dipyridamole at baseline did not receive the survival benefits of enalapril, whereas patients who received enalapril did not receive the survival benefits of aspirin. In a rather small study of 317 subjects with left ventricular systolic dysfunction (ejection fraction <35%) who were followed up for a relatively longer period of time (5.7 years), the favorable long-term prognosis of patients receiving aspirin was independent of receipt of an ACE inhibitor. A retrospective subgroup analysis of data from the CONSENSUS II study demonstrated that the 6-month mortality rate of patients with acute myocardial infarction (MI) who received enalapril and aspirin was higher than the combined mortality rates of patients receiving enalapril or aspirin alone. This strong interaction between aspirin and the ACE inhibitor enalapril suggests that the survival benefit of enalapril was significantly lower in patients also taking aspirin than in those taking enalapril alone. This interaction was not associated with other nonfatal major events. In the CATS study, use of low-dose aspirin (80 or 100 mg) did not attenuate beneficial effects of captopril (immediate and 1-year follow up) after acute MI. CONCLUSION: There is a theoretical possibility that the negative interaction between ACE inhibitors and aspirin may reduce the beneficial effects of ACE inhibitors in patients with heart failure, but the information obtained from the existing databases is limited by the retrospective nature of the analyses and does not establish the association definitively. Double-blind randomized controlled trials should be conducted to determine whether such a negative interaction indeed exists.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

A mandibular advancement device reduces sleep disordered breathing in patients with congestive heart failure.

Sleep disordered breathing (SDB) including obstructive and central sleep apnoea/hypopnoea as well as periodic breathing (PB) is common and is believed to increase risk for mortality in patients with congestive heart failure (CHF). Mandibular advancement device (MAD) has widely been recommended for treatment of obstructive sleep apnoea but the method has never been investigated for treatment of SDB in the patients with CHF. The aim with the present study was to examine the effect of MAD intervention on SDB in patients with CHF. The study included 17 male patients, aged 68.4+/-5.7 (mean+/-SD) with stable, mild to moderate CHF due to left ventricular systolic dysfunction and with SDB, expressed as apnoea/hypopnoea index (AHI) > or = 10. The SDB was examined during a single night using an unattended, portable polysomnographic device in the patients home, prior to and following intervention with a individually adjusted MAD. The SDB was evaluated by calculating AHI, PB expressed as the percentage of the total registration time, oxygen desaturation index (ODI) and snoring time. The AHI was reduced by MAD intervention from 25.1+/-9.4 to 14.7+/-9.7 (p=0.003). ODI reduced from 21.1+/-9.0 to 10.5+/-7.8 (p=0.007) and snoring time decreased from 53+/-111 to 18+/-47 seconds (p=0.02). PB was reduced from 55.7+/-25.6 to 40.4+/-26.4 per cent without statistical significance. In conclusion, the MAD intervention may be a feasible method for reducing SDB in patients with stable, mild to moderate CHF and left ventricular systolic dysfunction.

Aged↗
PubMed1989

Nifedipine administered after reperfusion ablates systolic contractile dysfunction of postischemic "stunned" myocardium.

Recent evidence suggests that postischemic contractile dysfunction of viable myocardium salvaged by reperfusion ("stunned myocardium") may be a consequence of abnormal calcium flux within the previously ischemic cells. Calcium channel blocking agents have been shown to enhance contractile function of stunned postischemic tissue, but it is not certain whether these improvements in function are due to the profound hemodynamic and vasodilator effects of these agents or to a direct effect on calcium flux within the stunned myocytes. Therefore, the effects of 1) high doses of nifedipine, given intravenously at 30 min after reperfusion, and 2) minute doses of nifedipine, infused directly into the coronary circulation at 30 min after reflow, were assessed and compared in anesthetized open chest dogs subjected to 15 min of transient coronary artery occlusion. As anticipated, intravenous nifedipine significantly reduced arterial pressure and increased regional myocardial blood flow. In addition, intravenous nifedipine restored systolic contractile function of the stunned, previously ischemic tissue to essentially normal preocclusion values: segment shortening averaged 102 +/- 8% versus 26 +/- 11% of baseline at 2 h after treatment in treated versus control dogs, respectively (p less than 0.003). Low dose intracoronary infusion of nifedipine did not alter hemodynamic variables or myocardial blood flow, but did improve segment shortening (90 +/- 9% versus 37 +/- 10% of preocclusion values at 1 h after treatment versus 25 min after reperfusion [that is, pretreatment], respectively; p less than 0.03). These data indicate that the calcium channel blocking agent nifedipine, given 30 min after reperfusion, enhances systolic contractile function of postischemic stunned myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group.

OBJECTIVES: The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure. BACKGROUND: Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy. METHODS: Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin. RESULTS: Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016). CONCLUSIONS: These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Body Weight↗
PubMed2004

Echocardiographic changes and risk factors for left ventricular hypertrophy in children and adolescents after renal transplantation.

Long-term consequences of cardiac alteration in children with chronic renal failure and after renal transplantation are largely unknown. In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular hypertrophy (LVH) or left ventricular dilatation. The correction of uremic state by renal transplantation leads to normalization of left ventricular contractility, regression of LVH and improvement of cavity volume and so dialysis patients with uremic cardiomyopathy would benefit from renal transplantation. We studied 73 patients, aged 17 yr or less, who underwent renal transplantation in our center. This cross-sectional study was performed 4.6 yr (median) after transplantation. Of the total, 48 were males and 25 were females. Transthoracic echocardiographic examination was performed for all cases. The effects of clinical, demographic, biochemical and therapeutic data on echocardiographic parameters were assessed. Multivariate analysis was used to assess the relation between the risk factors and the left ventricular muscle mass index. The most common echocardiographic abnormalities were the LVH (47.9%), left atrial enlargement (31.5%) and left ventricular dilatation and systolic dysfunction (13.7% for each). The pretransplant dialysis, arteriovenous fistula, acute rejection, cumulative steroid dose per square meter surface area, post-transplant hypertension, anemia and graft dysfunction were significant risk factors for LVH by univariate analysis. The significant factors by multivariate analysis were pretransplant dialysis, post-transplant hypertension and anemia. From this study we may conclude that LVH is a common problem among renal transplant children and adolescents. Early transplantation, control of hypertension and correction of anemia may be beneficial regarding left ventricular function and structure.

Adolescent↗
PubMed1997

When, and when not, to use digoxin in the elderly.

Digitalis has been widely used in the treatment of cardiac disease for more than 200 years. The present article reviews the current role of digitalis in the management of heart failure and atrial fibrillation (AF) in light of recent study findings. Generally, first-line therapy for the management of heart failure due to systolic dysfunction should include an ACE inhibitor and a diuretic. In patients who remain symptomatic despite the use of these drugs, the addition of digoxin should be considered. Because digoxin has been shown to reduce the number of hospital admissions attributable to worsening heart failure, more liberal use of digoxin in the management of heart failure may be justified. Digoxin may be adequate as monotherapy for ventricular rate control in patients with chronic AF, particularly in sedentary and elderly patients. A beta-blocker or calcium antagonist (either alone or in combination with digoxin) is indicated when digoxin is ineffective for ventricular rate control. Digoxin is ineffective in restoring sinus rhythm, preventing paroxysms or controlling rate in paroxysmal AF. The elderly are at an increased risk of digoxin toxicity. Low dosages of digoxin appear to be effective in the treatment of heart failure due to systolic dysfunction and may reduce the incidence of digitalis toxicity in these patients. In elderly patients with AF and inadequate rate control who are receiving digitalis monotherapy, adding another atrioventricular nodal blocking drug may be more appropriate than increasing the digoxin dose, in order to avoid toxic digoxin levels.

Aged↗
PubMed1986

Contribution of reduced mitral regurgitant volume to vasodilator effect in severe left ventricular failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy.

Although vasodilators improve cardiac output in severe left ventricular (LV) failure, the degree to which reduction in mitral regurgitation (MR) contributes to this response is unknown. In the present study, nitroprusside-induced changes in forward cardiac output were compared with simultaneous radionuclide LV output in 14 patients with severe LV systolic dysfunction in the absence of known primary valvular disease. Regurgitant output was estimated as LV output minus forward output and regurgitant fraction was calculated as regurgitant output/LV output. At rest, LV ejection fraction averaged 0.16 +/- 0.04 (mean +/- standard deviation). Patients were classified into 2 groups based on regurgitant fraction at rest. Group I (n = 5) had little or no detectable valvular regurgitation, with regurgitant fraction less than 0.10; group II (n = 9) had evidence of MR with regurgitant fraction greater than 0.30. Nitroprusside increased forward cardiac output in all patients in both groups, but this effect was significantly greater in group II (64 +/- 34%) than in group I (31 +/- 17%) (p less than 0.01). Nitroprusside decreased regurgitant fraction in all group II patients, with mean regurgitant fraction decreasing from 0.44 +/- 0.12 to 0.26 +/- 0.15 (p less than 0.005). Thus, a large percentage of patients with severe LV systolic dysfunction have clinically relevant MR, defined as a regurgitant fraction greater than 0.30. Nitroprusside has a greater effect on forward cardiac output in patients with LV failure and MR than in patients with comparable ventricular dysfunction in the absence of detectable MR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Underutilisation of ACE inhibitors in patients with congestive heart failure.

Congestive heart failure (CHF) is associated with substantial morbidity and mortality, and is the only major cardiovascular disease increasing in prevalence. Despite abundant evidence to support their efficacy and cost-effectiveness, angiotensin-converting enzyme (ACE) inhibitors are sub-optimally used in patients with CHF. This paper reviews the evidence for the sub-optimal use of ACE inhibitors in patients with CHF, the factors contributing to this, and its implications for health systems. A systematic review of all articles assessing practice patterns (specifically the use of ACE inhibitors in CHF) identified by MEDLINE, search of bibliographies, and contact with content experts was undertaken. 37 studies have documented the use of ACE inhibitors in patients with CHF. Studies assessing use among all patients with CHF document 33% to 67% (median 51%) of all patients discharged from hospital and 10% to 36% (median 26%) of community dwelling patients were prescribed ACE inhibitors. Rates of ACE inhibitor use range from 43% to 90% (median of 71%) amongst those discharged from hospital having known systolic dysfunction, and from 67% to 95% (median of 86%) for those monitored in specialty clinics. Moreover, the dosages used in the 'real world' are substantially lower than those proven efficacious in randomised, controlled trials, with evaluations reporting only a minority of patients achieving target doses and/or an overall mean dose achieved to be less than one-half of the target dose. Factors predicting the use and optimal dose administration of ACE inhibitors are identified, and include variables relating to the setting (previous hospitalisation, specialty clinic follow-up), the physician (cardiology specialty versus family practitioner or general internist, board certification), the patient (increased severity of symptoms, male, younger), and the drug (lower frequency of administration). In light of the substantial evidence for reductions in morbidity and mortality, clearly, the prescription of ACE inhibitors is sub-optimal. Wide variability in ACE inhibitor use is noted, with higher rates consistently reported among patients having systolic dysfunction confirmed by an objective assessment--an apparent minority of the those having CHF. Optimisation of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF by reducing hospitalisations and lengths of hospital stays. It is likely that only multifaceted programs targeted toward the population at large will yield benefits to the healthcare system, given the widespread nature of the sub-optimal prescription of therapies proven effective in the management of patients with CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Pharmacogenetic interactions between beta-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure.

BACKGROUND: Activation of the renin-angiotensin and sympathetic nervous systems adversely affect heart failure progression. The ACE deletion allele (ACE D) is associated with increased renin-angiotensin activation; however, its influence on patient outcomes remains uncertain, and the pharmacogenetic interactions with beta-blocker therapy have not been previously evaluated. METHODS AND RESULTS: We prospectively followed 328 patients (age, 56.1+/-11.9 years) with systolic dysfunction (left ventricular ejection fraction, 0.24+/-0.08) to assess the impact of the ACE D allele on transplant-free survival (median follow-up, 21 months). Transplant-free survival was compared by genotype for the whole cohort and separately in patients with (n=120) and those without beta-blocker therapy (n=208) at the time of entry. Transplant-free survival was significantly poorer for patients with the D: allele (1-year percent survival II/ID/DD=94/77/75; 2-year=78/65/60; ordered log-rank test, P:=0.044). In patients not treated with beta-blockers, the adverse impact of ACE D allele was dramatically increased (1-year percent survival II/ID/DD=95/75/67; 2-year=81/61/48; P:=0.005). In contrast, in patients receiving beta-blocker therapy, no influence of ACE genotype on transplant-free survival was evident (1-year percent survival II/ID/DD=91/80/86; 2-year=70/71/77; P:=0.73). CONCLUSIONS: In a cohort of patients with systolic dysfunction, the ACE D allele was associated with a significantly poorer transplant-free survival. This effect was primarily evident in patients not treated with beta-blockers and was not seen in patients receiving therapy. These findings suggest a potential pharmacogenetic interaction between the ACE D/I polymorphism and therapy with beta-blockers in the determination of heart failure survival.

Adrenergic beta-Antagonists↗
PubMed2005

[Prognosis of heart transplant candidates stabilized on medical therapy].

INTRODUCTION AND OBJECTIVES: A significant percentage of patients selected as candidates for heart transplantation can be stabilized by medical treatment, thereby enabling indefinite postponement of inclusion on the operation list. The aim of this study was to investigate the prognosis of these patients. PATIENTS AND METHOD: We studied retrospectively 118 patients with severe left ventricular systolic dysfunction (ejection fraction < or = 35%) who were consecutively evaluated for cardiac transplantation but who did not undergo transplantation because they became clinically stable on medical treatment. The mean follow-up period was 2.14 (2.19) years. Kaplan-Meier survival analysis, and univariate and multivariate Cox proportional risk analyses of factors predicting survival were performed. RESULTS: There were 18 deaths (15.2%): 12 were sudden (66.7%), 5 were due to heart failure (27.8%), and 1, to a non-cardiac cause (5.5%). The survival rate was 88% in the first year and 82% in the following 2 years. Univariate analysis showed that the parameters associated with mortality (P< or =.05) were pulmonary artery and capillary wedge pressures, diuretic treatment, and the absence of beta-blocker therapy. In the multivariate analysis, only the absence of beta-blocker therapy remained statistically significant (P=.003; RR = 0.13; 95%CI, 0.03-0.50). CONCLUSIONS: In a population of patients with severe left ventricular systolic dysfunction who were candidates for heart transplantation but who were stabilized by medical therapy, mortality during the first year of follow-up was 12%. Beta-blocker therapy was the only variable associated with better survival.

Algorithms↗