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Background: Beta-blockers are underused in HF patients, thus strategies to implement their use are needed., Objectives: To improve beta-blocker use in elderly and/or patients with severe heart failure (HF) and to evaluate safety and outcome., Methods: Patients with symptomatic HF and age>/=70 years or left ventricular EF<25% and symptoms at rest were enrolled, including those already on beta-blocker treatment. Patients who were not receiving a beta-blocker were considered for carvedilol treatment. All patients were followed up for 1-year., Results: Of the 1518 elderly patients, 505 were already on beta-blockers, and carvedilol was newly prescribed in 419 patients. At 1-year, patients treated with carvedilol had a lower incidence of death [10.8% vs. 18.0% in already treated (adjusted RR 0.68; 95%CI 0.49-0.96) and 11.2% in newly treated patients (adjusted RR 0.68; 95%CI 0.48-0.97)]. Of the 709 patients with severe HF, 38.4% were already on beta-blockers, and carvedilol was newly prescribed in 189 patients. Patients not treated with carvedilol showed the worst clinical outcome. Total rate of discontinuation (including adverse reaction and non-compliance) was 14% and 9%, respectively, in elderly and severe patients., Conclusions: In a real world setting, beta-blocker treatment was not associated with an increased risk of adverse events in elderly and severe HF patients.

The magnitude of benefit on mortality of combined angiotensin-converting enzyme inhibitor (ACEI) and beta-blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent-to-treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val-HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow-up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure-related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year.

Background and Aims: It is well known that beta-blockers are useful in patients with chronic heart failure (CHF). These favourable effects have recently been observed even in elderly CHF patients. Objectives of the present study were to evaluate the feasibility, tolerability and safety of carvedilol therapy in a cohort of patients > 70 years of age with CHF and left ventricular ejection fraction < 40% with chronic atrial fibrillation. For this purpose, we designed an observational, 12-month prospective study., Results: Among 240 patients who were referred to our centers and met inclusion criteria, 64 had chronic atrial fibrillation (27%). Thirty-nine out of these 64 subjects (61%) were treated with carvedilol, while 25 patients (39%) had contraindications to such treatment. In the cohort of 176 patients with stable sinus rhythm (control group), carvedilol could be administered in 121 patients (69%), while it was not given in 55 (31%, p=ns). Airways disease was the main reason for exclusion from carvedilol in this setting of patients. No difference in 1-year tolerability of study drug was observed among patients with chronic atrial fibrillation (29 of 33 patients=87.9%) and stable sinus rhythm (95 of 102=93.1%). Adverse events leading to the discontinuation of carvedilol in these two populations were rare and never resulted in any disability, death or were life-threatening., Conclusion: In over-70 patients with systolic CHF, chronic atrial fibrillation does not limit the possibility of testing beta-blocker therapy. Carvedilol was equally tolerated and safe in patients with atrial fibrillation and sinus rhythm.

Background and Aim: Mitral regurgitation (MR) has been demonstrated to be a powerful predictor of adverse outcome in middle-aged patients with chronic heart failure (CHF). In this study, we sought to define the prognostic impact of functional mitral regurgitation in a population of elderly patients with systolic CHF., Methods: One hundred seventy-five outpatients aged >70 years with validated CHF and left ventricular ejection fraction <40% underwent clinical and echocardiographic evaluations at baseline. Mitral regurgitation was diagnosed by Color Doppler and quantified in 5 categorical values using a 0-4+ grading system. Outcome measures included 1-year mortality and hospitalization for worsening CHF., Results: The distribution of patients according to the 5 different degrees of MR detected at baseline was: absent=11%, 1+=31%, 2+=38%, 3+=16%, 4+=4%. The relationship between MR and mortality was direct and approximately linear (r=0.39, p=0.00001). The prevalence of death in the 5 subgroups was 0%, 7%, 15%, 45%, 57%, respectively. Multivariate logistic regression analysis showed that MR was the strongest predictor of death (OR 4.47, 95% CI 1.50-13.0), independently of the presence of diabetes mellitus, older age and larger left ventricular end-diastolic volume. No association was found between MR and hospitalization for worsening CHF (r=0.08, p=0.41)., Conclusions: This study establishes the direct and independent relationship between MR severity and one-year mortality among elders with systolic CHF. Conversely, MR does not provide useful information regarding the risk of subsequent hospitalization for worsening CHF.

Aims: Anaemia is often observed in patients with chronic heart failure (CHF), and it may be associated with a worse prognosis. Aim of this study was to identify the individual mechanisms of anaemia in CHF patients., Methods and Results: One hundred and forty-eight consecutive patients with haemoglobin concentration <13 g/dL (if males) or <12 g/dL (if females) were enrolled. Factors responsible for anaemia were investigated by evaluating endogenous erythropoietin (Epo) production, serum cytokines levels, body iron status, and iron supply for erythropoiesis. Most patients (57%) presented anaemia of chronic disease and among them, 92% showed evidence of a defective endogenous Epo production. This was indicated by an observed/predicted log(serum Epo) ratio less than 0.8 and/or a defective iron supply for erythropoiesis diagnosed by low transferrin saturation and/or increased value of soluble transferrin receptor. According to regression analysis sex, renal failure, and serum Epo were correlated with anaemia., Conclusion: According to our study, about half of anaemic CHF patients showed anaemia of chronic disease with blunted endogenous Epo production and/or a defective iron supply for erythropoiesis. Determination of the individual mechanisms of anaemia in CHF could justify a rational therapeutic approach to anaemia.

Background and Aims: In recent years, reversal of established left ventricular (LV) dilatation has been increasingly recognized in middle-aged patients with dilated cardiomyopathy receiving angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers. We performed this prospective study to evaluate whether optimized therapy for heart failure also induces LV reverse remodeling in older patients., Methods: One hundred and twenty-four patients aged >70 years with LV ejection fraction <40% underwent clinical and echocardiographic evaluation at baseline and after 1 year. During the early stage of follow-up, pharmacological therapy was optimized. LV reverse remodeling was defined as a reduction in LV end-diastolic volume >25% from baseline to final evaluation., Results: LV reverse remodeling was recognized in 32 patients (26%). Compared to the subjects who did not improve LV geometry, those with reverse remodeling had, at baseline, higher arterial blood pressure, lower serum creatinine levels, shorter duration of symptoms of heart failure, more frequently received beta-blocker therapy and had predominantly nonischemic aetiology. The variables associated with the development of reverse remodeling in the multivariate analysis were shorter duration of symptoms of heart failure (Odds ratio: 7.7; CI: 2.5-23.3, p=0.0001) and beta-blocker therapy (Odds ratio: 6.0; CI: 1.6-23.3, p=0.01)., Conclusions: LV reverse remodeling takes place in elderly as well as in younger heart failure patients. A significant proportion of elderly patients undergoes this favourable process which occurs prevalently in patients receiving beta-blocker therapy with a short history of cardiac disease.

The importance of studying the pathophysiological bases and clinical correlates of exercise limitation in patients with pulmonary arterial hypertension (PAH) is well established. Two modes of exercise testing, the 6-min walk test (6MWT) and the cardiopulmonary exercise test (CPET), are currently proposed for diagnostic, therapeutic and prognostic finalities. The 6MWT is inexpensive, feasible and is thought to better reproduce daily life activities and to reliably detect therapeutic benefits. CPET requires the patient's maximal effort and does not provide a reliable quality of life measure. It is, however, highly reproducible and provides remarkable insights into the pathophysiological mechanisms that lead to exercise intolerance. Due to the limited experience accumulated, CPET is not actually advised for the routine assessment and for the overall clinical decision making of PAH patients. In this review we critically address the knowledge currently acquired on these techniques.

Background: Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia., Methods and Results: Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions., Conclusions: Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

Background: No clinical investigation provided any information about a possible influence of atrial fibrillation on the response to beta-blocker therapy in elderly patients with chronic heart failure (CHF). The aim of this study was to observe carvedilol effects in a cohort of patients > 70 years of age with CHF due to left ventricular dysfunction and with chronic atrial fibrillation., Methods: An observational, 12-month prospective clinical and echocardiographic study was carried out on 240 patients > 70 years of age with heart failure due to systolic dysfunction, 64 of whom with atrial fibrillation., Results: After 1 year of beta-blocker treatment, patients with atrial fibrillation and those in sinus rhythm showed similar benefits, in terms of symptomatic improvement (deltaNYHA -0.44 if atrial fibrillation vs -0.57 if sinus rhythm, p = NS), reduction of events (death + hospitalizations -38 vs -15%), recovery of cardiac function (left ventricular ejection fraction delta +8.8 vs +9.4%, p = NS; left ventricular end-diastolic volume delta -17.2 vs -12.5 ml, p = NS), and reduction in mitral regurgitation (delta -042 vs -0.57, p = NS). No difference was found between the two study groups regarding left ventricular end-diastolic volume reduction (12% in atrial fibrillation patients and 18% in sinus rhythm patients, p = NS) and prevalence of the "reverse remodeling" phenomenon (22 and 21%, respectively, p = NS)., Conclusions: In CHF patients > 70 years of age, beta-adrenergic blockade was shown to be equally effective in improving symptoms and left ventricular geometry and function in patients with atrial fibrillation or in sinus rhythm, without any adjunctive sign of long-term clinical deterioration.

Background: Aims of the present study were (1) to confirm the prognostic role of anemia in patients with heart failure (HF) and (2) to analyze this aspect in relatively unselected patients with HF monitored prospectively in a community setting (IN-CHF), and in patients selected for enrollment into the Valsartan Heart Failure Trial (Val-HeFT)., Methods and Results: In both Val-HeFT and IN-CHF Registry, anemia was defined as a hemoglobin (Hb) level < or = 11 g/dL in women and < or = 12 g/dL in men. Of the 2411 patients of the IN-CHF Registry, 15.5% had anemia, whereas in the 5010 patients of the Val-HeFT trial, the prevalence was 9.9%. In the IN-CHF registry, 1-year all-cause mortality was significantly higher in anemic patients (25.9%) than in patients without anemia (13.2%) (P < .0001). The association of anemia with mortality was confirmed by the multivariable analysis (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20-1.97). The risk of death decreased by 9.7% for each gram of Hb. The Val-HeFT trial showed an all-cause mortality rate for anemic patients of 29.6% over a mean follow-up period of 22.4 months versus 18.5% (P < .0001) in patients without anemia. After adjustment, anemia retained its negative independent prognostic role (HR 1.26, 95% CI 1.04-1.52). When Hb was considered as a continuous variable, the risk of death decreased by 7.8% for each gram of Hb., Conclusions: Anemia was confirmed to be an independent negative prognostic factor in patients with HF. This finding is consistent in 2 different clinical contexts, a controlled trial and a registry in clinical practice, in which patient characteristics and outcome are largely different.

Background: In the assessment of myocardial infarction (MI) mass, contrast-enhanced magnetic resonance imaging (CE-MRI) is comparable to single-photon emission computed tomography (SPECT). The aim of the present study was to determine whether the MI area, as assessed at CE-MRI and SPECT, is comparable to mass evaluation. We also compared CE-MRI and SPECT estimates of the MI area with functional evaluations made at echocardiography and kinetic MRI (cine-MRI)., Methods: We used a 1.0 Tesla MRI scanner and an inversion-recovery turboFLASH sequence, a tomographic gamma-camera and second-harmonic ultrasound systems. Two blinded operators assessed the extent of scarring, expressed as a percentage of the whole left ventricle (LV), using a 16-segment model. We studied 55 consecutive patients with a clinically stable healed MI (50 Q wave, 5 non-Q wave)., Results: The scar mass was 19+/-23% of the LV at CE-MRI and 21+/-25% at SPECT; the scar area was 29+/-23% of the LV at CE-MRI, 41+/-28% at SPECT, 29+/-31% at cine-MRI, and 32+/-29% at echocardiography. The Bland-Altman bias between CE-MRI and SPECT mass estimations was -2% of the LV with a+/-23% limit of agreement (LOA), while the bias between the area assessments was -12% with a+/-42% LOA. Bias between CE-MRI and functional evaluation by cine-MRI and echocardiography was 0% with a+/-39% LOA and -3% with a+/-36% LOA respectively. Comparing SPECT with cine-MRI and echocardiography the bias was 12% with a+/-52% LOA and 9% with a+/-56% LOA respectively., Conclusions: CE-MRI has proved to be comparable to SPECT in the assessment of the healed MI mass. Conversely, a high systematic error (high bias and LOA) renders CE-MRI and SPECT assessments of the MI area incomparable. Similarly (high bias and/or LOA) CE-MRI and SPECT estimations of the MI area cannot be compared with functional evaluation by echocardiography or cine-MRI.

We compared contrast-enhanced MRI (CeMRI) with the most widely used imaging techniques for myocardial infarct (MI) diagnosis, SPECT and Echo, in unselected patients with chronic coronary artery disease (CAD). Two blinded operators assessed scars on MRI, SPECT and Echo images using a 16-segments LV model. We studied 105 consecutive patients: 50 had Q-wave MI (Q-MI), 19 non Q-wave MI or rest angina (nonQ-MI/RA) and 36 effort angina (EA) history. CeMRI was positive, respectively, in 96%, 37%, and 6%, SPECT in 90%, 53%, and 44%, and Echo in 84%, 32%, and 28% of patients (within Q-MI: CeMRI vs. SPECT p < 0.03, vs. Echo p < 0.001; within EA CeMRI vs. SPECT and ECHO p < 0.001; all trends p < 0.001, pseudo r-square: 0.56-0.75 for CeMRI, 0.18-0.28 for SPECT and 0.23-0.37 for Echo). CeMRI and SPECT agreed in 83 patients (79%); negative SPECT with 1 +/- 0 segments subendocardial delayed enhancement (DE) was found in 4 (4%); negative CeMRI with 4 +/- 3 segments perfusion defects in 18 (17%), 16 of whom were obese or showed LBB or sub-occlusion of related coronary. CeMRI and Echo agreed in 78 patients (75%); negative Echo with 2 +/- 1 segments subendocardial DE was found in 13 (12%) and negative CeMRI with 11 +/- 7 segments kinetic abnormalities in 14 (13%), in 10 confirmed by Cine-MRI. In Q-MI, CeMRI detects DE more frequently than perfusion defects and, especially, kinetic abnormalities are found by SPECT and Echo, respectively. CeMRI identifies small areas of DE also in some patients with nonQ-MI or RA but usually not in patients with EA. This biologically plausible decreasing trend is shown by CeMRI more clearly than by SPECT and Echo. Disagreement between CeMRI and SPECT or Echo may be reduced, but perhaps not fully eluded, performing dobutamine Echo and SPECT after maximal epicardial coronary dilatation.

Background: Although the process by which the left ventricular (LV) remodels in response to an injury generally leads to dilatation, in patients with heart failure (HF) the recognition of a small or mildly dilated left ventricle is not uncommon. We investigated the prevalence and the characteristics of elderly patients with traditional dilated and nondilated cardiomyopathy (CMP). We also assessed the response to the guideline-based medical therapy and the prognosis based on LV dilatation in this population., Methods and Results: We selected 243 patients >70 years of age with HF and LV ejection fraction <40% who underwent clinical and echocardiographic evaluations at baseline and after 12 months. They were subdivided into 2 groups according to baseline LV end-diastolic volume (LVEDV) (values < or =78 mL/m(2) identified nondilated CMP). Nondilated CMP was recognized in 64 patients (26%) who showed at baseline better clinical status, less severe mitral regurgitation, and higher LV ejection fraction than those with dilated CMP. At the final evaluation, favorable changes in clinical and echocardiographic parameters could be detected in both groups. The magnitude of these variations did not differ between the groups. The risk of hospitalization for worsening HF was 2.4-fold higher in patients with nondilated than dilated CMP. Mortality was 11% and 20%, respectively (P = .06). Statistical analysis revealed a direct, approximately linear relationship between LVEDV and outcomes in this population., Conclusions: A total of 1 of 4 elderly patients with systolic HF had a nondilated left ventricle. These patients had a better clinical presentation than did counterparts with dilated left ventricles. After HF therapy is optimized, the likelihood of improvement is independent of LV size in this population, whereas the risk of death or worsening HF linearly increases with LV dilatation.

Even if improved, the prognosis of chronic heart failure is still malignant, survival rate being similar to that of cancer. Due to the relevant epidemiology of the disease in the elderly, the terminal care of heart failure has a significant impact. Improving end-of-life care (by improving quality of life, quality of cure and care at the end of life and quality of dying and death) is a major challenge for health providers involved in heart failure care.

Clinical trials investigating traditional inotropic agents in patients with heart failure demonstrated an increased mortality rate (odds ratio 1.50; IC=0.51-3.92), high incidence of discontinuation of infusion therapy (odds ratio 0.46; IC=0.083-2.29) due to major side effects and, most of all, a limited clinical benefit (odds ratio 0.75; IC=1.42-0.08). On this background a new class of inotropic drugs, the calcium-sensitisers, have been developed. The safety and efficacy of levosimendan (Simdax) has been recently demonstrated in trials (LIDO e RUSSLAN) in patients with heart failure due to ischemic and not ischemic disease. Twenty-six patients with decompensated heart failure of different etiology have been treated with 24 hour infusion of levosimendan. In this experience the levosimendan improved the clinical status and the left ventricular ejection fraction.

Background: Current guidelines recommend beta-blockers in patients with heart failure and left ventricular systolic dysfunction. These agents, however, are largely underused in elderly patients because of the perception of up-titration complexity and the fear of side effects., Methods: We prospectively assessed the feasibility, safety, tolerability, and 1-year outcome of the in-hospital initiation of carvedilol in elderly patients admitted for worsening heart failure., Results: Among 164 eligible subjects (age > 70 years, left ventricular ejection fraction < 40% and no sign of congestion), 120 (73%) received carvedilol, on average 4.5 days after admission. The drug was permanently withdrawn in 10 out of 116 survivors (9%) at 60 days: 5 did not tolerate the starting dose because of worsening heart failure (n = 1), bradycardia (n = 1), and bronchospasm (n = 3). Two discontinued carvedilol during the in-hospital dose titration phase because of increasing premature ventricular beats and transient second degree atrioventricular block. The remaining 3 dropouts (fatigue in 2 and symptomatic bradycardia in 1 case) occurred after discharge. During the period between 60 days and 12 months, carvedilol was discontinued in 2 patients because of a depressive syndrome and symptomatic bradycardia. In no case these adverse events lead to death or were life-threatening, required hospitalization or resulted in any disability. The 1-year tolerability was 89%, the mortality was 17.5%, the frequency of hospitalization for worsening heart failure was 21%., Conclusions: Thus, our results show that the in-hospital initiation of carvedilol is feasible and well-tolerated in elderly patients with recent worsening heart failure, and allows rapid identification of the most intolerant patients. The proportion of subjects taking carvedilol after 1 year from discharge was very high. This unconventional approach could significantly modify the use of beta-blockers in clinical practice.

Background: Chronic heart failure (CHF) is a progressive process requiring complex therapeutic interventions. Recently, several trials documented the clinical improvement and regression of left ventricular (LV) remodeling and function in patients on optimized CHF treatment. Furthermore, some authors reported isolated cases of patients who apparently "healed" from CHF. The aim of the present study was to characterize the phenomenon of the normalization in clinical status and LV size and function in CHF patients., Methods and Results: We monitored the clinical and echocardiographic parameters of a large cohort of patients with CHF and LV ejection fraction <40% every 6 months for a mean period of 17 +/- 9 months. Twenty of 110 study patients (18%) normalized clinical status and LV size and ejection fraction at any time (mean time 13 +/- 6 months) during the follow up. Such condition, however, was subsequently lost in 11 patients. The normalization was predicted by the nonischemic etiology of CHF, arterial hypertension, absence of diabetes mellitus, carvedilol therapy, and the dose of carvedilol., Conclusions: The normalization in clinical status and LV size and function is not infrequently observed in patients on optimal CHF therapy. It is predicted by a set of clinical variables and favored by beta-blocker therapy. At medium term, this condition fades in a significant portion of patients.

In patients with decompensated chronic congestive heart failure (CHF), intensive unloading therapy allows an acute decrease in ventricular filling pressures and improves long-term prognosis. Because elderly patients do not routinely undergo invasive hemodynamic evaluation, they are generally denied such a pharmacologic approach. We prospectively characterized the acute hemodynamic response to intensive unloading and its prognostic significance in a elderly population with CHF who were hospitalized for cardiac decompensation. Fifty-nine patients aged >70 years with left ventricular systolic dysfunction underwent intensive unloading therapy (furosemide and nitroprusside) tailored to reduce ventricular filling pressures to near-normal levels. The hemodynamic parameters were monitored by Doppler echocardiography. At baseline, left and right ventricular filling pressures were 21 +/- 3 and 10 +/- 3 mm Hg, respectively. Although all patients experienced a relevant improvement in clinical status during hospital stay, a significant reduction of ventricular filling pressures was detected at discharge in only 40 of them (68%) (responders), whereas 19 patients (32%) had a deficient response to therapy (nonresponders). This unfavorable behavior was predicted by the presence of renal dysfunction at admission. During 19-month follow-up, death due to cardiovascular causes occurred in 8 of 40 responders (20%) and in 9 of 19 nonresponders (47%) (p <0.005). Hospitalizations for cardiovascular causes were more frequent in the nonresponders (58% vs 8%, p <0.0001). Thus, a deficient hemodynamic response to intensive unloading treatment is not infrequent in elderly patients with decompensated CHF. This behavior is predicted by renal dysfunction at admission and is associated with poorer outcome.

Background: Little is known about the clinical profile, use of resources, management and outcome of a large population of diabetic patients with heart failure managed in a community setting., Methods: A prospective cross-sectional survey in the setting of acute hospital admissions for heart failure to 167 cardiology and 250 internal medicine departments between February 14 and 25, 2000., Results: Among the 2127 consecutively admitted patients, 603 (28.4%) had a history of diabetes; they were significantly younger, had a lower rate of atrial fibrillation, and a more frequent ischemic etiology than non-diabetics. Just as non-diabetic patients, diabetics underwent invasive and non-invasive procedures in a low percentage of cases, even though slightly more frequently when managed by cardiologists. Diabetic patients were less frequently prescribed amiodarone and anticoagulants, and more frequently prescribed nitrates and antiplatelets. The all-cause in-hospital mortality rate was similar among diabetics and non-diabetics (5.3 vs 5.7%, p = NS). Adjusted analysis confirmed that diabetes is not independently associated with a worse outcome., Conclusions: In a community setting diabetes per se has only a slight impact on the management and outcome of patients with heart failure.

Background: The purpose pf the current article is to describe the clinical profile, use of resources, management and outcome in a population of real-world inpatients with heart failure., Methods and Results: With a prospective, cross-sectional survey on acute hospital admissions, we evaluated the overall and provider-related differences in patient characteristics, diagnostic work-up, treatment and inhospital outcome of 2127 patients with heart failure admitted to 167 cardiology departments and 250 internal medicine departments between February 14 and 25, 2000. Patients admitted to cardiology units were younger (56.3% >70 years vs 76.2%, P <.0001), had more severe symptoms (NYHA IV 35% vs 29%, P =.00014), and more often underwent evaluation of ventricular function (89.3% vs 54.8%, P <.0001) and coronary angiography (7.5% vs 0.9%, P <.0001) than those admitted to medical units. Moreover, they were more often prescribed beta-blockers (17.8% vs 8.7%, P <.0001). However, prescription of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (78.7% vs 81.5%, P = not significant [NS]) and inhospital mortality (5.2% vs 5.9%, P = NS) were similar. A 6-month follow-up visit was performed in 56.4% of cases (68.2% of cardiology vs 49.4% of medicine patients, P <.0001); 6-month readmission (43.7% vs 45.4%, P = NS) and mortality (13.9% vs 16.7%, P = NS) rates were similar., Conclusions: Patients with heart failure admitted to cardiology and internal medicine units represent 2 clearly different populations. In both groups, diagnostic procedures and evidence-based treatments, such as beta-blockers, appeared to be underused, and there was a lack of structured follow-up, as well as a poor 6-month prognosis.

Recent studies have suggested some gender-related differences in the incidence, quality of care, response to therapy, and outcome in heart failure patients. The majority of studies have proposed a better survival for women compared to men. However, the under-representation of women in clinical trials leads to some uncertainty regarding the survival benefit. Some data suggest the possibility that ACE-inhibitors may be less beneficial in women as compared to men. Beta-blockers seem to be effective both in women and men. Further studies are needed to clarify whether these differences may have a pathophysiological basis.

Background: Physicians are still concerned about prescribing beta-blockers in diabetic patients with heart failure., Methods: In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start beta-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on beta-blockers, 28% started treatment at the enrollment visit, and 47% were not started on beta-blockers., Results: The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with beta-blockers, diabetic patients treated with beta-blockers, nondiabetic patients not treated with beta-blockers, nondiabetic patients treated with beta-blockers) showed that patients treated with beta-blockers had a higher event-free probability than patients not treated with beta-blockers regardless the presence of diabetes (P <.0001)., Conclusions: On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from beta-blockers even if at a lower degree. Thus, there are no justifications to avoid beta-blockers in heart failure patients in the presence of diabetes.

Background: Diuretics are the cornerstone of treatment for the congestive symptoms of heart failure (HF). Despite their widespread use, diuretic prescription data in clinical practice are scarce. In this study we evaluated the prescription pattern of diuretics in a large population of HF outpatients, enrolled by a national network of hospital-based cardiologists., Methods and Results: Among 11070 HF outpatients (mean age 64 +/- 12 years, 72.9% men, 29.8% New York Heart Association [NYHA] class III-IV, mean left ventricular ejection fraction [LVEF] 35+/-12%), 9247 took a diuretic, the most frequently prescribed therapeutic agent (83.5%). Loop diuretics were prescribed alone (65.5%) or combined with other diuretics in 91.6% of patients. By multivariate analysis, the strongest independent predictors of diuretic use were a previous hospital admission for HF (odds ratio [OR] 2.55, 95% confidence interval [CI] 2.28-2.86), NYHA class III-IV (OR 2.52, 95% CI 2.14-2.96), LVEF < 30% (OR 1.87, 95% CI 1.57-2.24). Aldosterone antagonists were prescribed to 2142 patients (23.1%); independent predictors of their use overlapped with those of diuretics and moreover included treatment with loop diuretics (OR 3.52, 95% CI 2.66-4.66) and digoxin (OR 1.45, 95% CI 1.29-1.64)., Conclusions: In this wide series of stable HF outpatients, cardiologists prescribed diuretics in accordance with published guidelines. Evolving prescription patterns of aldosterone-receptor blockers need to be further evaluated.

Unlabelled: For quality-of-care assessment of rehabilitation programs after cardiac surgery, measures of functional recovery have been proposed as outcome indicators. Aim of this study was to evaluate the feasibility, the safety and the informative content of the 6-min walking test (6 WT) performed in elderly patients soon after admission in an intensive rehabilitation program after cardiac surgery., Methods: Population consists of 115 consecutive over-70 patients admitted to an in-hospital rehabilitation program after cardiac surgery. Within 7 days of admission, in 107 patients (93%) clinical conditions allowed the execution of a 6 WT, on ECG telemetry monitoring. Resting and exertional heart rate, score of fatigue (Borg Scale 1 divided by 20), symptoms, ECG alterations and arrhythmias were recorded. Other considered variables were: comorbidity (Charlson index), length of stay and complications occurring during the whole surgical and rehabilitation in-hospitalisation stay, disability (nursing needs: Maslow and nursing chart), functional status at discharge, left ventricular ejection fraction, number of exercise treatment sessions, self-perceived health-status at admission and at discharge (EuroQoL questionnaire)., Results: The mean walked distance was 194 +/- 93 m. No complication neither ECG alteration occurred during the 6 WT; only isolated premature ventricular beats were recorded in 26 pts. Heart rate increased from 86 +/- 13 at rest to 95 +/- 17 bpm at the end of the 6 WT (p < .0001). The perceived fatigue score was 12.9 +/- 1.2 Borg. Complications, length of stay, nursing needs, self-perceived health-status and functional capacity at discharge differed between patients who performed the 6 WT within 4 days compared with those who did it later, and between patients who walked < or = 120 m (lower quartile) compared with those who walked more., Conclusions: In elderly patients after cardiac surgery the 6 WT performed within the first week of admission in rehabilitation unit is feasible and safe. Simple cut-offs like timing of the 6 WT and walking performance identify more severe patients with lower susceptibility to recovery.

Sudden death is one of the more important cause of mortality in patients with chronic heart failure. The highest risk occurs among patients with less severe functional impairment, whereas patients in NYHA class IV usually die of progression of heart failure. Predictors of sudden death have been evaluated. Nevertheless, current methods of risk stratification for sudden death are still inadequate, especially in patients with advanced heart failure. Low left ventricular ejection fraction is widely used for the risk stratification, but it lacks of sensitivity and specificity in distinguishing patients with an increased arrhythmic mortality from those with an increased mortality due to pump failure. Unsustained ventricular tachycardia and inducibility at electrophysiological study may help identifying high-risk patients, requiring more aggressive therapy, as the ICD implantation. Heart rate variability and baroreflex sensitivity analysis have been utilized to obtain information on autonomic modulation, but with uncertain conclusion on the identification of high-risk patients. Increased QT dispersion, the presence of T-wave alternans and abnormal signal-averaged electrocardiography have also been proposed, but, up-to-now, any of these parameters showed a strong predictor power. In conclusion, our capability to identifying heart failure patients at risk for arrhythmic death is still far from being satisfactory.

Although improved, the prognosis of chronic heart failure is still malignant, the survival rate being similar to that of cancer. Due to the relevant epidemiology of this disease, the terminal care of heart failure has a significant impact, searching for the best quality of cure and care.

Significant differences between sexes may influence the prevalence, incidence and severity of the heart failure syndrome. These differences may also interfere with treatment and management. In this review sex differences and similarities have been analyzed focusing on epidemiology, drug therapy and psychological implications. Pathophysiological differences but also a selection bias are evident; such differences bear an influence on clinical management. Gender differences exist even in the health-related quality of life, depression and coping ability. No studies have been specifically designed to investigate gender differences and the exclusion of elderly persons (mainly women) from large trials may compromise the quality of their care.

Background: Despite the well-established benefits of ACE-inhibitors in chronic heart failure (CHF), current treatment rates and prescribed doses are lower than those proven to improve survival. We evaluated whether participation in a specialist network and the use of a common database would impact on the compliance with CHF guidelines., Methods: We analyzed the rate and determinants of ACE-inhibitor use and prescribed doses among 8102 patients with CHF enrolled at 133 cardiology centers participating in a national network., Results: 6625 patients (82%) took ACE-inhibitors, most commonly enalapril (41%, mean dose 16 +/- 9 mg), captopril (25%, mean dose 74 +/- 44 mg) and lisinopril (14%, mean dose 13 +/- 8 mg). The predictors of the non-prescription of ACE-inhibitors were: female gender (odds ratio--OR 1.46, 95% confidence interval-CI 1.28-1.67), older age (OR 1.01, 95% CI 1.01-1.02), valvular etiology (OR 1.87, 95% CI 1.60-2.20), NYHA class III-IV (OR 1.25, 95% CI 1.09-1.42) and creatinine levels > 2.5 mg/dl (OR 5.19, 95% CI 3.36-8.02). Conversely a left ventricular ejection fraction < 30% (OR 0.78, 95% CI 0.65-0.94) and a hypertensive (OR 0.69, 95% CI 0.55-0.86) or idiopathic (OR 0.67, 95% CI 0.57-0.78) etiology increased the rate of ACE-inhibitor prescription. Low ACE-inhibitor doses were prescribed to 26.4% of cases., Conclusions: The IN-CHF database, an educational and organizational effort led by a national cardiology society, demonstrates that high rates of ACE-inhibitor treatment may be achieved in routine clinical practice in a cardiology setting.

Background: The aim of this study was to evaluate the clinical characteristics, 1-year prognosis and therapeutic approach of heart failure with a preserved left ventricular systolic function in a large multicenter registry of patients referred to specialized heart failure clinics., Methods: The study population consisted of 5164 outpatients (mean age 62 +/- 12 years, 78.8% male, 28.1% in NYHA functional class III-IV) with an available left ventricular ejection fraction (LVEF) measurement at the initial evaluation for enrollment in the Italian Network on Congestive Heart Failure. A 1-year follow-up was available for 2390 patients., Results: 2859 out of 5164 patients (55.4%) had an LVEF < 35%, 1618 (31.3%) had an LVEF between 35 and 45%, and 687 patients (13.3%) had an LVEF > 45%. Patients with an LVEF > 45% were significantly older, more often female and presented a significantly higher prevalence of a hypertensive etiology, obesity and atrial fibrillation. The severity of the clinical picture, as indicated by a lower prevalence of NYHA class III-IV (17.2 vs 35.6%, p = 0.001) and a third heart sound (14.8 vs 33.5%, p = 0.001), was less in patients with an LVEF > 45%. The therapeutic approach differed significantly, with a larger use of calcium antagonists and beta-blockers in patients with an LVEF > 45%, while ACE-inhibitors, diuretics and digoxin were more often prescribed to those with an impaired LVEF. The 1-year mortality and morbidity (all cause and congestive heart failure worsening hospitalizations) were significantly lower in patients with a preserved left ventricular systolic function compared to those with left ventricular systolic dysfunction (8.9 vs 18.8% for mortality, p = 0.001, and 8.3 vs 16.5% for hospital readmissions due to worsening congestive heart failure, p = 0.001, respectively)., Conclusions: Patients with congestive heart failure and a preserved left ventricular systolic function seem to constitute a distinct population not infrequently presenting even in the clinical setting of specialized heart failure clinics. Further studies are needed to establish a definitive and standardized diagnosis and the most appropriate therapy for congestive heart failure with a normal LVEF.

Chronic heart failure shows an increasing prevalence and extremely high rate of both hospital admission and readmission. Thus, in recent years there has been a growing interest in the development of more effective strategies for disease management. The existing literature shows programs involving multidisciplinary teams, specialized clinics, that employ a systematic approach and provide continuity of care, frequently involving a specialized nurse dedicated to comprehensive management. These experiences reported a favourable effects on clinically relevant outcome, including readmission, quality of care and cost of care. A recent randomized trial conducted by Krumholtz and colleagues emphasises the importance of patient's education and support intervention, without medical management components. This model was effective in reducing readmissions and in-hospital costs. On the basis of these data, patients education and support should be considered a "non-pharmacological therapy" for heart failure patients.

Unlabelled: The recovery process in the elderly after cardiac surgery is influenced not only by clinical cardiac conditions, but also by comorbidity, cognitive decline and disability. We evaluated the relationship between clinical objective and self-perceived factors and their influence on functional recovery in 204 consecutive, over-70s pts who were admitted into an intensive hospital rehabilitation program following cardiac surgery. The variables taken into consideration were: comorbidity (Charlson index), length of hospital stay and complications in cardiac surgery and rehabilitation, disability (nursing needs score index), functional status (6-min walking test), left ventricular EF, number of training sessions, self-perceived health status (EuroQol questionnaire), emotional impairment (anxiety/depression, CBA-2.0/interview)., Results: Functional capacity: the distance walked was 198 +/- 103 m at admission and 287 +/- 121 m at discharge (p < 0.0001). Only the nursing needs score index resulted as a weak, independent predictor of the distance walked at admission (r2 = 0.14, p < 0.001, beta = 0-.21), which (beta = 0.49), together with complications during rehabilitation (beta = -0.15), self-perceived health status at discharge (beta = 0.15) and number of training sessions (beta = 0.20), was independently correlated with the distance walked at time of discharge (r2 = 050, p < 0.0001). Patients mood: anxiety correlated with depression. Emotional scores did not correlate with functional measures. Patients self-perceived health status: only the nursing needs score index was a weak, independent predictor of well-being at entry (r2 = 0.15, p < 0.0001, beta = -0.29), which, in turn, was the only predictor of perception at discharge (r2 = 0.33, p < 0.0001, beta = 0-.42)., Conclusions: In an intensive hospital rehabilitation program following cardiac surgery in patients over 70 a) there was no correlation between clinical and psychological variables; b) anxiety and depression were associated, but neither influenced the recovery process nor correlated to health status perception; c) functional impairment was strongly influenced by nursing needs which also affected the self-perceived health status; d) both functional and perception recovery were influenced by disability at time of admission and reacted positively after rehabilitation.

Background: In spite of its clinical importance, cognitive functioning is not always taken into account in studies on patients with chronic heart failure. The aim of the present study is to analyse the relationship between cognitive impairment and cardiovascular variables in a sample of patients with chronic heart failure for assessment or candidated for heart transplant., Methods: Sixty-four male patients with chronic heart failure in NYHA class I-III, in a stable clinical condition, underwent cardiological evaluation and neuropsychological assessment by means of a wide battery of tests: Spinnler and Tognoni's tests and WAIS scale., Results: Compared to the normative group, only 9% of patients did not have impairment in any cognitive function. 26% of patients had impairment of one cognitive function, and 30% of four or more cognitive functions. The cognitive functions that were most often impaired were short-term verbal memory, short-term visual spatial memory, differed verbal memory and verbal learning and visual spatial logical ability. On the whole, no statistical significant relationship was found between cognitive scores and the considered cardiovascular variables., Conclusions: Our data support the need to take into account the risk of cognitive impairment in CHF patients, regardless of age, disease severity or functional status. The high prevalence of short-term verbal memory impairment has important implications in clinical practice, since CHF patients should be actively involved in the medical management of their disease. Memory deficits could compromise patient's adherence to treatment as well as doctor-patient interactions. The practical consequences of these difficulties require some changes in doctors' behaviour and suggest the need for specific medical staff member training.

Background: A deleterious effect of complete left bundle-branch block (LBBB) on left ventricular function has been established. Nevertheless, the independent effect of a widened QRS on mortality rate in congestive heart failure (CHF) is still controversial. Therefore, we carried out this analysis to determine whether LBBB is an independent predictor of mortality in CHF., Methods and Results: We analyzed the large Italian Network on CHF Registry of unselected outpatients with CHF of different causes. The registry was established by the Italian Association of Hospital Cardiologists in 1995. Complete 1-year follow-up data were available for 5517 patients. The main underlying cardiac diagnosis was ischemic heart disease in 2512 patients (45.6%), dilated cardiomyopathy in 1988 patients (36.0%), and hypertensive heart disease in 714 patients (12.9%). Other causes were recorded in the remaining 303 cases (5.5%). LBBB was present in 1391 patients (25.2%) and was associated with an increased 1-year mortality rate from any cause (hazard ratio, 1.70; 95% confidence interval, 1.41 to 2.05) and sudden death (hazard ratio, 1.58; 95% confidence interval, 1.21 to 2.06). Multivariate analysis showed that such an increased risk was still significant after adjusting for age, underlying cardiac disease, indicators of CHF severity, and prescription of angiotensin-converting enzyme inhibitors and beta-blockers., Conclusion: LBBB is an unfavorable prognostic marker in patients with CHF. The negative effect is independent of age, CHF severity, and drug prescriptions. These data may support the rationale of randomized trials to verify the effects on mortality rate of ventricular resynchronization with multisite cardiac pacing in patients with CHF and LBBB.

In the progressive understanding of the heart failure syndrome different models have followed. Current pathophysiology model suggests that heart failure is a neurohormonal disorder: an abnormality in cardiac function and a disturbance in myocardial contractile force is the initiating event in heart failure, and the clinical expression and progression of the disease occurs as a result of subsequent extracardiac alterations. Treatment with drugs capable of antagonizing the effects of neuroendocrine activation, such as angiotensin-converting enzyme inhibitors, beta-blockers and antialdosterone agents have induced a significant reduction in morbidity and mortality in heart failure patients. The progressive understanding of the circulating homeostasis mechanisms moved from the systemic to the paracrine aspects of the neurohormonal systems and contributed to the development of new drugs. Moreover, the analysis of a drug's development can be an important step in the medical knowledge advancement. In this sense, aldosterone and spironolactone became an interesting "case", which is analyzed in this paper, going through the steps that have promoted the spironolactone from a weak diuretic to a neurohormonal drug and, finally, to a "central" drug.

Background: Congestive heart failure (HF) represents a major public health problem with an age-related increasing prevalence. Despite the high mortality and morbidity in elderly patients with HF, limited clinical and prognostic data are available for development of appropriate prevention and treatment strategies., Methods: A cohort of 3327 outpatients consecutively enrolled in the Registry of Italian Network on Congestive Heart Failure by 133 cardiology centers was studied. Univariate and multivariate analyses were performed to compare patients <70 and > or =70 years old and to evaluate associations between clinical variables and the 1-year mortality rate and hospitalizations., Results: With respect to the 2294 patients <70 years old, the 1033 (31%) elderly patients were significantly more likely to be female, to be in New York Heart Association (NYHA) class III-IV, and to have preserved left ventricular systolic function (ejection fraction >40%), an ischemic/valvular etiology, and atrial fibrillation/flutter. Elderly patients received angiotensin-converting enzyme inhibitors, beta-blockers, and anticoagulants less frequently than younger patients did. The 1-year mortality rate was significantly higher in patients > or =70 years old (22% vs 13.7%, P <.001). Age was an independent predictor of 1-year mortality, increasing 2.8% by each year of age. Independent predictors of 1-year mortality in elderly patients were (1) > or =1 hospital admission in the previous year (relative risk [RR] 2.09, 95% CI 1.51-2.87), (2) systolic blood pressure (RR 0.98, 95% CI 0.97-0.99), (3) NYHA class III-IV (RR 1.57, 95% CI 1.20-2.07), and (4) age (RR 1.028, 95% CI 1.001-1.056)., Conclusions: Our study confirms that elderly patients (1) are seen in a more advanced stage of HF, (2) are less likely to receive evidence-based treatments, (3) show more frequently preserved systolic function, and (4) have a worse prognosis. Consequently, there is a need to develop more effective and targeted management strategies for this escalating health problem.

The challenge of preventing arrhythmic sudden death is one of the major issues of today's treatment of heart failure. To pursue this aim, an accurate selection of candidates for sudden death has to be routinely carried out, while a maximized and individualized drug treatment has to be extensively administered in all high-risk selected patients. However, in clinical practice there is no agreement on the selection criteria of sudden death risk, particularly in patients with advanced heart failure. Furthermore, the real impact of each category of drugs in reducing the risk of sudden death in heart failure patients is still under debate. As far as non-pharmacological options are concerned, implantable cardioverter-defibrillators (ICD) have been demonstrated to be the most effective therapy in patients with prior cardiac arrest due to ventricular fibrillation or poorly tolerated ventricular tachycardia. Low left ventricular ejection fraction, unsustained ventricular tachycardia and inducibility at electrophysiological study also may identify high-risk patients requiring ICD implantation. However, such a stratification seems to be effective in ischemic more than in non-ischemic patients, while generally the primary prevention of sudden death is still restricted to a minority of patients. Biventricular pacing has been proven to be effective in optimizing left ventricular function in more than 50% of left bundle branch block and advanced heart failure patients, while further studies are needed to evaluate the real impact of cardiac resynchronization therapy on hard endpoints, such as survival and long-term clinical outcome. Therefore, the selection criteria of "responders" to this novel non-pharmacological therapy still have to be defined. There is convincing evidence in the literature that tailored drug therapy can be highly effective in preventing heart failure progression as well as in reducing total and sudden mortality. Nevertheless, prevention of sudden death is still a debated point in heart failure treatment. For this reason, we aimed to provide heart failure specialists with updated reviews on this topic, such as those published in this issue of the Italian Heart Journal Supplement. Therefore, we are proud to present all the authors who contributed with the high quality of their articles to this editorial effort. Obviously, we have to thank the authors, but we also have to address the readers, thanking them in advance for their interest in such an initiative.

In the management of chronic heart failure there is increasing evidence that effective communication with the patient is an important tool in health care since it permits the achievement of therapeutic goals and the patient's satisfaction in terms of the quality of health assistance received. In fact, the variations in the communication processes relevantly influence the results in some behaviors and attitudes of the patient, such as adherence to the therapeutic prescriptions, understanding and remembering the information received, satisfaction with the medical examination and less worry. The capacity of the patient of co-administering the illness may result in a reduction in the instability due to avoidable concomitant factors, and thus reduce the heart failure morbidity and rehospitalization rate. Building up an effective doctor-patient relationship becomes an important goal to achieve, and the necessary instruments are not only instinctive or the result of experience, but can also be taught and learnt. The aim of this work was to give a contribution, which, in addition to underlining the theoretic aspects of the communicative process by means of numerous examples taken from everyday practice in patient management, is to induce reflection and to propose ways of intervention for the improvement of the therapeutic relationship between the cardiologist and the patient with heart failure.

The six-minute walking test (WT) is used in trials and clinical practice as an easy tool to evaluate the functional capacity of chronic heart failure (CHF) patients. As WT measurements are highly variable both between and within individuals, this study aims at assessing the contribution of the different sources of variation and estimating the reproducibility of the test. A statistical model describing WT measurements as a function of fixed and random effects is proposed and its parameters estimated. We considered 202 stable CHF patients who performed two baseline WTs separated by a 30 minute rest; 49 of them repeated the two tests 3 months later (follow-up control). They had no changes in therapy or major clinical events. Another 31 subjects performed two baseline tests separated by 24 hours. Collected data were analysed using a mixed model methodology. There was no significant difference between measurements taken 30 minutes and 24 hours apart (p = 0.99). A trend effect of 17 (1.4) m (mean (SE)) was consistently found between duplicate tests (p < 0.001). REML estimates of variance components were: 5189 (674) for subject differences in the error-free value; 1280 (304) for subject differences in spontaneous clinical evolution between baseline and follow-up control, and 266 (23) for the within-subject error. Hence, the standard error of measurement was 16.3 m, namely 4 per cent of the average WT performance (403 m) in this sample. The intraclass correlation coefficient was 0.96. We conclude that WT measurements are characterized by good intrasubject reproducibility and excellent reliability. When follow-up studies > or = 3 months are performed, unpredictable changes in individual walking performance due to spontaneous clinical evolution are to be expected. Their clinical significance, however, is not known., (Copyright 2000 John Wiley & Sons, Ltd.)

In this part the most updated indications for evidence-based counseling of cardiac patients during pregnancy, labor and the postpartum period are reviewed. Moreover, indications and contraindications for the use of some cardiac drugs during pregnancy and lactation are provided.

Background: In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear., Objective: To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations., Methods: Forty-five consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared., Results: After 6 months of treatment with carvedilol, left ventricular ejection fraction had increased from 24% +/- 7% to 29% +/- 9% (P <.0001); this change was caused by a reduction in end-systolic volume index (106 +/- 41 vs 93 +/- 37 mL/m(2); P <. 0001). Deceleration time of early diastolic filling increased (134 +/- 74 vs 196 +/- 63 ms; P <.0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no significant changes in deceleration time of early diastolic filling were found (139 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 +/- 25 vs 16 +/- 13 mL; P <.0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume (r = -.57, P <.0001). These findings were not observed in patients in the control group., Conclusions: The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.

Heart failure (HF) is rapidly becoming one of the most prevalent cardiovascular disorders; the incidence of HF is expected to continue to increase in the years to come. The peculiarities of the syndrome require special approaches from the point of view of both clinical management and research methodology. As far as clinical management, new models based on a multidisciplinary approach and continuity of care should be implemented. The methodology of epidemiological research should take into account the complexity of the syndrome, the high frequency of comorbid conditions, the advanced age of typical patients, and the spreading of HF patients among different health care providers and specialists. In this paper, a general epidemiological view of HF is reported and studies of clinical epidemiology carried out in Italy in the area of HF are described. (c) 1999 by CHF, Inc.

In patients with chronic heart failure (CHF) and a "peak summation" left ventricular pattern, no hemodynamic and prognostic information can be drawn from Doppler examination of mitral flow. In 263 consecutive patients with CHF who were undergoing simultaneous right heart catheterization and echo-Doppler examination, we prospectively determined (1) the frequency of the peak summation left ventricular filling pattern and (2) the incremental information contributed by pulmonary venous flow velocity patterns in providing noninvasive hemodynamic profile estimation. Isovolumic relaxation time of mitral flow, peak systolic (X), diastolic forward (Y), reverse (Z) flow velocity, and systolic fraction (X/X + Y) of pulmonary venous flow were measured. Forty-six of 263 (17%) patients had a peak summation left ventricular filling pattern. This subgroup showed more clinical deterioration (New York Heart Association functional class III-IV, 57% vs 49%; P < 0.01) and left atrial dysfunction (left atrial ejection fraction, 31% vs 39%; P < 0.001). However, 40% of these patients had a pulmonary wedge pressure of <18 mmHg and a cardiac index of >2.2 L/min/m(2). The systolic fraction of peak velocities of pulmonary venous flow showed a good correlation with pulmonary wedge pressure (r = -0.70, P < 0.05). The correlation was stronger in patients without mitral regurgitation (r = -0.81, P < 0.05). A systolic fraction of <40% was accurate (sensitivity, 100%; specificity, 95%) in identifying patients with a pulmonary wedge pressure of >18 mmHg. In patients without mitral regurgitation, this variable was also correlated with cardiac index (r = -0.65, P < 0.05) and predicted a cardiac index of >2.2 L/min/m(2) (sensitivity, 91%; specificity, 71%). In conclusion, a peak summation left ventricular filling pattern is common in patients with CHF. Pulmonary venous flow provides useful information about the hemodynamic profile of these patients.

A computer-based system integrated into the hospital information system for the pharmacological management of the chronic heart-failure patients admitted to the heart-failure unit of Montescano is presented. The major aims of the system involved monitoring the patients' treatment history and the related therapeutic decision-making. The treatment history of the first 151 consecutive CHF patients admitted after the system implementation is examined. The prescribed drug doses at admission and at discharge are compared, as well as the differences in etiology and NYHA class between patients discharged with or without each drug. Several considerations can be drawn from this analysis. First of all, in heart failure patients the choice of drugs is limited and optimal treatment is a result of individualized dosages. Secondly, time and trials are necessary to obtain optimal treatment. Consequently, continuity of care and in- and out-hospital networks are advisable. Third, a computer-based system offers advantages not only for the pharmacological management itself, but also for improving the quality of care through continuous analysis of the decision-making process.