Search

Background: Myocardial rupture is a relatively rare and usually fatal complication of myocardial infarction (MI). Early recognition of patients at greatest risk of myocardial rupture provides an opportunity for early intervention., Methods: VALIANT was a double-blind, randomized, controlled trial comparing valsartan, captopril, and their combination in high-risk patients post-MI. Myocardial rupture was identified by autopsy (available in 138/589 patients dying within 30 days of index MI), echocardiography, direct surgical visualization, or presence of hemopericardium. An independent clinical end points committee reviewed medical records for all deaths or suspected nonfatal cardiovascular events., Results: Rupture was identified in 45 (0.31%) patients enrolled in VALIANT, occurring 9.8 +/- 6.0 days after the qualifying MI. Rupture accounted for 7.6% (45/589) of all deaths occurring in the first 30 days of follow-up and 24% (33/138) of deaths in which autopsies were obtained. Compared with survivors, rupture was associated with increased age, hypertension, increased Killip class, lower estimated glomerular filtration rate, and Q wave MI, and inversely related to beta-blocker and diuretic use. Compared with patients who died of other causes within 30 days, patients with myocardial rupture were more likely to have had an inferior MI, Q wave MI, or hypertension; to have used oral anticoagulants; or to have received thrombolytic therapy., Conclusions: Although rare, myocardial rupture accounted for nearly one fourth of all deaths within the first 30 days after high-risk MI, suggesting an estimated incidence of approximately 1% within the first 30 days. A number of clinical characteristics may identify post-MI patients at higher risk of myocardial rupture., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Several surveys show that patients with chronic heart failure (CHF) are sub-optimally managed and treatment guidelines are not implemented in clinical practice., Aims: To investigate awareness and perceptions of the 2005 European Society of Cardiology (ESC) guidelines for CHF., Methods: 467 cardiologists from seven European countries completed an on-line interview using a validated, semi-structured questionnaire including questions about awareness and relevance of CHF guidelines. To assess agreement with ESC guidelines, three fictitious patient cases were presented and respondents' management choices compared with those of an expert panel based on the guidelines., Results: Awareness of CHF guidelines was high, with 98% aware of any guideline and 65% aware of ESC guidelines. ESC guidelines were considered relevant (51%) or very relevant (38%) for guiding treatment decisions. Up to 92% of respondents perceived that they adhered to the ESC guidelines. For the patient cases,

Aims: To assess the relationship between body mass index (BMI), mortality and mode of death in chronic heart failure (CHF) patients; to define the shape of the relationship between BMI and mortality., Methods and Results: We performed a post-hoc analysis of 5010 patients from the Valsartan Heart Failure Trial. The end-points of the study were all-cause and cardiovascular mortality. Mortality rate was 27.2% in underweight patients (BMI<22 kg/m2), 21.7% in normal weight patients (BMI 22-24.9 kg/m2), 17.9% in overweight patients (BMI 25-29.9 kg/m2) and 16.5% in obese patients (BMI>30 kg/m2) (p<0.0001). The rates of non-cardiovascular death did not differ among groups. The risk of death due to progressive heart failure was 3.4-fold higher in the underweight than in the obese patients (p<0.0001). Normal weight, overweight and obese patients had lower risk of death as compared with underweight patients (p=0.019, HR 0.76, 95% CI 0.61-0.96; p=0.0005, HR 0.68, 95% CI 0.55-0.84; p=0.003, HR 0.67, 95% CI 0.52-0.88, respectively) independently of symptoms, ventricular function, beta-blocker use, C-reactive protein and brain natriuretic peptide levels., Conclusions: In CHF patients a higher BMI is associated with a better prognosis independently of other clinical variables. The relationship between mortality and BMI is monotonically decreasing.

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.

Background: Loop diuretics are beneficial in heart failure in the short term because they eliminate fluid retention, but in the long-term, they could adversely influence prognosis due to activation of neurohumoral mechanisms., Aims: To explore the changes induced by diuretic withdrawal in chronic nonadvanced heart failure., Methods: Diuretics were withdrawn in 26 stabilized heart failure patients with systolic dysfunction (ejection fraction [EF]<45%). Clinical status was evaluated by physical exam, exercise capacity (corridor test) and New York Heart Association (NYHA) class. Biochemical and neurohumoral determinations were performed at baseline and at 3 months., Results: At 3 months, 17 out of 26 patients (65%) were able to tolerate diuretic interruption without a deterioration in exercise capacity or New York Heart Association functional class. Renal function parameters improved (baseline urea 46.2+/-10.8 to 39.2+/-10.1 mg/dl at 3 months, p=0.014; creatinine 1.1+/-0.23 to 0.98+/-0.2 mg/dl, p=0.013). Glucose metabolism also improved (fasting glucose 151+/-91 to 122+/-14 mg/dl, p=0.035). Heart rate and systolic blood pressure did not significantly change, while diastolic blood pressure increased (from 80+/-10 to 87+/-13 mm Hg, p=0.006). Neurohumoral determinations showed a decrease in plasma renin activity (4.19+/-5.96 to 2.88+/-4.98 ng/ml, p=0.026), with no changes in aldosterone, arginine-vasopressin, endothelin-1 and norepinephrine. In contrast, atrial natriuretic peptide significantly increased (115+/-87 to 168+/-155 pg/ml, p=0.004)., Conclusion: Diuretic withdrawal in stabilized heart failure with systolic dysfunction is associated with an improvement in renal function parameters, glucose metabolism and some neurohumoral parameters, such as plasma renin activity; however, atrial natriuretic peptide levels increased.

Aims: Large randomized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure. The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain. The SENIORS study was performed to assess effects of the beta-blocker, nebivolol, in patients >/=70 years, regardless of ejection fraction., Methods and Results: We randomly assigned 2128 patients aged >/=70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction 35%), and 68% had a prior history of coronary heart disease. The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg. The primary outcome occurred in 332 patients (31.1%) on nebivolol compared with 375 (35.3%) on placebo [hazard ratio (HR) 0.86, 95% CI 0.74-0.99; P=0.039]. There was no significant influence of age, gender, or ejection fraction on the effect of nebivolol on the primary outcome. Death (all causes) occurred in 169 (15.8%) on nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71-1.08; P=0.21)., Conclusion: Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.

Background: Management guidelines for heart failure recommend ACE-I and beta-blockers. The perception of difficult up-titration might have added to the slow uptake of beta-blockers despite their mortality and morbidity benefits., Aims: CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination., Methods: Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril., Results: There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively., Conclusion: The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril.

Aims: Heart failure (HF) treatment guidelines of the ESC recommend ACE-inhibitors (ACE-I) as first-line treatment and beta-blockers added if patients remain symptomatic. CARMEN explored the need for combined treatment for remodelling and order of introduction by comparing the ACE-I enalapril against carvedilol and their combination., Methods: In a parallel-group, 3-arm study of 18 months duration, 572 mild heart failure patients were randomly assigned to carvedilol (N = 191), enalapril (N = 190) or their combination (N = 191). In the latter, carvedilol was up-titrated before enalapril. Left ventricular (LV) remodelling was assessed by transthoracic echocardiography (biplane, modified Simpson) at baseline and after 6, 12 and 18 months of maintenance therapy. Primary comparisons considered the change in LV end-systolic volume index (LVESVI) from baseline to month 18 between the combination and enalapril, and between carvedilol and enalapril., Results: In the first primary comparison, LVESVI was reduced by 5.4 ml/m2 (p = 0.0015) in favour of combination therapy compared to enalapril. The second primary comparison tended to favour carvedilol to enalapril (NS). In the within treatment arm analyses, carvedilol significantly reduced LVESVI by 2.8 ml/m2 (p = 0.018) compared to baseline, whereas enalapril did not. LVESVI decreased by 6.3 ml/m2 (p = 0.0001) with combination therapy. All three arms showed similar safety profiles and withdrawal rates., Conclusion: CARMEN is the first study to demonstrate that early combination of ACE-I and carvedilol reverses LV remodelling in patients with mild to moderate HF and LV systolic dysfunction. The results of the CARMEN study support a therapeutic strategy in which the institution of beta-blockade should not be delayed.

Introduction and Objectives: To assess baseline characteristics, management patterns, and clinical outcomes after 18 months in patients diagnosed as heart failure in a tertiary hospital in Catalonia, Spain., Methods: The records of all 265 patients admitted to the Hospital General Vall d'Hebron from July through December 1998 with a diagnosis of heart failure who met study criteria were identified and analyzed. Patients were interviewed by telephone 18 months later., Results: The mean age of the study population was 75 12 years, 42% were male, 19% were admitted for causes other than heart failure, and 62% had significant comorbidity. Ventricular function was assessed in 68% (preferentially patients with a better prognosis), and was considered normal in 41%. Angiotensin-converting enzyme inhibitors or angiotensin II antagonists were used in 54%, and beta-blockers in 4%. The 18-month mortality was 46% (77% cardiac mortality). Multivariate predictors of death were older age, severe or previous heart failure, and serious comorbidity. At 18 months, 69% of survivors were in functional classes I or II., Conclusions: 1) As in other geographic areas, patients in this study were an older population with poor survival; 2) local patterns of care definitely need improvement; 3) comorbidity is important for prognosis, and 4) a significant proportion of survivors enjoy an acceptable quality of life long after discharge.

Surveys of prescribing in both hospitals and primary care have shown delays in translating improved survival data from clinical trials into clinical practice thereby denying patients the benefits of proven treatments, such as the angiotensin converting enzyme inhibitors. This may be due to unfamiliarity with clinical guidelines and concerns about adverse events. Recent trials have shown that substantial improvements in survival are associated with spironolactone and beta-blocker therapy. In order to accelerate the uptake of these treatments, and to ensure that all eligible patients should receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of heart failure. The objective of these recommendations is to provide practical guidance for non-specialists in order to support the implementation of evidenced-based therapy for heart failure. These practical recommendations are meant to supplement rather than replace existing guidelines.

Aims: To evaluate the clinical characteristics and long-term outcomes of advanced heart failure patients (NYHA Class IIIb-IV) receiving beta-blocker therapy vs. those patients not receiving beta-blockers at randomization in the FIRST trial, a randomized, double-blind, placebo-controlled trial of epoprostenol vs. usual care in advanced heart failure., Methods and Results: The patient population consisted of 471 patients enrolled in FIRST with Class IIIb-IV heart failure, left ventricular ejection fraction (LVEF) of <30%, advanced hemodynamic abnormalities, and standard pharmacologic treatment of ACE-inhibitor, diuretics, and/or digoxin. The study cohort consisted of 448 patients not receiving beta-blockers and 23 patients receiving beta-blockers at randomization for the FIRST trial. Patients in the beta-blocker group had decreased rates of any clinical event (P = 0.03), worsening heart failure (P = 0.001), and death or worsening heart failure (P = 0.0008) than patients not receiving beta-blockers. After adjusting for prognostically important variables, the favorable effect of beta-blockers on worsening heart failure (P = 0.02) and death or worsening heart failure (P = 0.02) persisted., Conclusion: Patients with advanced heart failure who receive beta-blocker therapy have a lower rate of hospitalization and are less likely to experience worsening heart failure or death at 6 months than patients who are not treated with beta-blockers. These observational data contribute to the growing body of data demonstrating a favorable effect of beta-blockers on clinical outcomes in heart failure.

The recently reported Digitalis Investigation Group (DIG) study has shown that digoxin has no demonstrable effect on survival in heart failure, but may be useful to ameliorate morbidity. The question may be raised whether digoxin is useful for symptomatic improvement in patients with mild or moderate heart failure. A major difficulty in answering this question is the lack of appropriate clinical measures of heart failure that allow a categorization such as mild, moderate and severe heart failure. However, data in several clinical trials permit an approach to this issue in an approximate way. For instance, the DIG study itself indicated that the beneficial clinical effect of digoxin was also apparent in pre-defined subgroups which corresponded to less severe forms of heart failure. The problem with the DIG study in this respect was the lack of direct measures of clinical improvement and the use of what might be taken as surrogates for these; however, it can probably be assumed that digoxin had a beneficial symptomatic effect even in patients with milder forms of heart failure. Direct clinical measures of clinical result were used in the Randomized Assessment of the effect of Digoxin on Inhibitors of ACE Study and the Prospective Randomized Study on Ventricular Failure and the Efficacy of Digoxin. Some inconsistencies between the clinical results of these trials may be explained partly on the basis of sample size, although on the whole the results point to a definite clinical improvement of patients on digoxin therapy, even when heart failure was considered to be mild on the basis of several measurements. Admittedly, the size of the effect of digoxin therapy in these patients may be quite modest. Although some concerns over safety may remain after the DIG trial, it can generally be accepted that digoxin is an effective drug for symptomatic improvement in patients with mild or moderate heart failure. The small size of this effect, however, indicates that the decision to use the drug may well be left to the discretion of the attending physician.

This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.

Heart failure is a physiopathological condition, with an increasing incidence and prevalence, involving the action of a series of mechanisms known as "compensators", which are phylogenetically ready to normalize minute volume and blood pressure. These mechanisms include the activation of a series of neurohormonal systems: the sympathetic nervous system, the aldosterone renin-angiotensin system, vasopressin arginine, endothelin, which are basically vasoconstrictors, with the counterpoint of other vasodilator systems, such as the endothelial relaxation factor, certain prostaglandins and the bradykinin-kallikrein system, which modulate global response. The authors review the physiopathology of each of these system, as well as their significance in the diagnosis and prognostic evaluation of heart failure. We analyze the possible deleterious effects of neurohormonal activation, anatomically and at cardiovascular function level, and try to determine if they are capable of explaining the evolution and progression of heart failure, in a truly vicious circle, up until the irreversible heart failure phase. We review the current importance of the inhibition of the aldosterone renin-angiotensin system in the prophylaxis and treatment of heart failure. Furthermore, we describe the present-day value of the inhibition of the sympathetic nervous system in some forms of heart failure. We also analyze the different pharmacological treatments for heart failure: diuretics, inotropic agents, vasodilators (in their different pharmacological types), paying particular attention to their action on neurohormonal systems and their implications in the prognosis and evolution of heart failure.

Heart failure is a physiopathological condition, with an increasing incidence and prevalence, involving the action of a series of mechanisms known as "compensators", which are phylogenetically ready to normalize minute volume and blood pressure. These mechanisms include the activation of a series of neurohormonal systems: the sympathetic nervous system, the aldosterone renin-angiotensin system, vasopressin arginine, endothelin, which are basically vasoconstrictors, with the counterpoint of other vasodilator systems, such as the endothelial relaxation factor, certain prostaglandins and the bradykinin-kallikrein system, which modulate global response. The authors review the physiopathology of each of these systems, as well as their significance in the diagnosis and prognostic evaluation of heart failure. We analyze the possible deleterious effects of neurohormonal activation, anatomically and at the cardiovascular function level, and try to determine if they are capable of explaining the evolution and progression of heart failure, in a truly vicious circle, up until the irreversible heart failure phase. We review the current importance of the inhibition of the aldosterone renin-angiotensin system in the prophylaxis and treatment of heart failure. Furthermore, we describe the present-day value of the inhibition of the sympathetic nervous system in some forms of heart failure. We also analyze the different pharmacological treatments for heart failure: diuretics, inotropic agents, vasodilators (in their different pharmacological types), paying particular attention to their action on neurohormonal systems and their implications in the prognosis and evolution of heart failure.

Clinical and electrocardiographic features of 227 patients who died of an acute myocardial infarction (AMI) were compared with those of 150 survivors of a first AMI. Left ventricular (LV) free wall rupture was found in 93 patients aged > 50 years, but not in 134. The incidence of healed infarct (4 [4%] vs 50 [37%], p < 0.001), heart failure (11 [12%] vs 112 [84%], p < 0.001), and bundle branch block (11 [12%] vs 54 [40%], p < 0.001) was lower in patients with than without LV rupture. In patients with anterior AMI and early rupture (1 day), admission ST elevation was higher than in those with late LV rupture (> 1 day, 6.8 +/- 4.0 vs 4.0 +/- 2.7 mm, p < 0.01). However, lateral wall AMI had minimal ST elevation and accounted for 10% of ruptures. On day 2, the decrease in ST segment in patients with late LV rupture was less than in survivors (0.5 +/- 1.6 vs 3.2 +/- 2.9 mm, p < 0.001). Admission systolic blood pressure in patients who had early rupture was higher than in survivors (155 +/- 22 vs 137 +/- 22 mm Hg, p < 0.001) and in those with late rupture (135 +/- 23 mm Hg, p < 0.001). Late rupture was associated with infarct thinning and triggered by a physical strain in 18 of 45 patients (40%); infarct thinning, however, was present only in 4 of 48 patients (8%) with early rupture (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Ten healthy (aged 28 to 39) and ten heart failure NYHA II (aged 19 to 49) male subjects were prospectively studied under no drugs, under furosemide (40 mg/day), under captopril (150 mg/day) and under their association. Arterial compliance (ml/mmHg) was measured in all subjects at rest and supine. Heart failure etiology was dilated cardiomyopathy or ischemic heart disease without significant regurgitation. Arterial compliance was significantly higher in healthy than in heart failure patients in all studied conditions (p less than 0.001) (healthy = 2.2 + 0.29 vs. heart failure = 0.79 + 0.14). Neither single drug nor their association induced any change in healthy subjects. Arterial compliance progressively increased in heart failure with furosemide, captopril, and their association (no drug = 0.79 + 0.14; furosemide = 0.87 + 0.15; captopril = 0.94 + 0.15 and furosemide + captopril = 0.99 + 0.14). Captopril induced a higher increment than furosemide (p less than 0.001) and their association even a higher increment (p less than 0.001) than any single drug. Thus captopril and/or furosemide increased arterial compliance in heart failure but not in healthy subjects, possibly through changes in arterial wall edema and smooth muscle contraction.

A case of a transient and huge postanterior acute myocardial infarction left ventricular thrombus causing temporary intractability of severe heart failure is reported. Echographic and hemodynamic data suggest the restrictive-obliterative pattern of heart failure.

An abstract of the study "Specialist Awareness of and Adherence to Clinical Guidelines for Management of Chronic Heart Failure (CHF)," by M. Komajda and colleagues, is presented.

Iron depletion was suggested to be protective against the development of ischemic heart disease. Population studies have led to conflicting results, and such an association has not been addressed in patients with heart failure due to cardiomyopathy. We studied the distribution of hemochromatosis-related mutations in 319 patients with heart failure due to cardiomyopathy of different etiologies. The genotypic distribution showed a significantly higher prevalence of heterozygotes for the C282Y mutation in patients with ischemic cardiomyopathy than in patients with cardiomyopathy of nonischemic etiologies (p = 0.0036). The frequency of the D63 mutation was not significantly different between ischemic versus nonischemic groups. In multiple logistic regression models adjusted for age, sex, ethnicity, and different degrees of disease progression, there was a strong and significant association of the C282Y mutation with ischemic cardiomyopathy compared with the nonischemic group (odds ratio 6.64, 95% confidence interval 1.71 to 25.73, after adjustment). In our sample, genetic variation in the HFE gene was associated with ischemic cardiomyopathy. Such association merits further study regarding its value as a prognostic marker in patients with ischemic heart disease. [ABSTRACT FROM AUTHOR]