Renata De Maria

Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds--the TEMISTOCLE study.

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.

Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark

Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001).

Alcohol abuse and dilated cardiomyopathy in men

Excessive ethanol intake is reported in 3% to 40% of patients with idiopathic dilated cardiomyopathy (IDC). In the prevasodilator era, the prognosis was reportedly better in alcoholic than in IDC patients, an advantage limited to abstinent patients. No large series of patients systematically treated with angiotensin-converting enzyme inhibitors has since been described. We analyzed long-term outcome according to alcohol abuse in male patients with IDC. Among 338 men who had been prospectively enrolled in a multicenter registry, 79 (23%) were defined as alcohol abusers and further classified at follow-up as having stopped (AAS) or continued (AAC) abuse. AAC subjects at enrollment reported a higher daily alcohol intake than AAS subjects (178 +/- 113 vs 127 +/- 54 g/day, p = 0.012). During a mean of 59 +/- 35 months, 102 patients died and 45 underwent transplantation. Seven-year transplant-free survival was significantly lower in alcohol abusers (41%) than in patients with IDC (53%, p = 0.026), and significantly lower in AAC subjects (27%) than in either patients with IDC or AAS (45%) (p = 0. 018). Although IDC patients had beneficial changes in left ventricular function at follow-up, only AAS patients had significant improvement in ejection fraction. In this large series of patients treated with angiotensin-converting enzyme inhibitors and prospectively followed up, excessive alcohol intake was found in about one fourth of cases and persistent alcohol abuse correlated with a worse prognosis and function at follow-up.

Comparison of clinical findings in idiopathic dilated cardiomyopathy in women versus men

Clinical and laboratory findings were compared in 65 women and 238 men with invasively documented idiopathic dilated cardiomyopathy. Women had more severe symptoms (New York Heart Association class > or = III in 48 vs 39%; p < 0.05), presented more frequently with heart failure signs (63 vs 41%; p < 0.01), and had a higher cardiothoracic ratio (0.56 +/- 0.06 vs 0.53 +/- 0.06; p < 0.05) and higher frequency of left bundle branch block (41 vs 29%; p < 0.05). Echocardiographic measurements in women showed significantly greater left ventricular (LV) end-diastolic (42 +/- 7 vs 39 +/- 6 mm/m2; p < 0.0001) and end-systolic (36 +/- 7 vs 33 +/- 6 mm/m2; p < 0.001) diameters, and mean myocardial thickness (11 +/- 2 vs 10 +/- 2 mm; p < 0.05). Exercise duration was shorter in women than in men (7 +/- 3 vs 10 +/- 4 minutes; p < 0.001). After 18 +/- 16 months, 9 women and 27 men died, and 7 and 17, respectively, received transplants. Transplant-free survival was not significantly different according to gender. By Cox multivariate analysis, LV ejection fraction was a significant independent predictor of cardiac death or heart transplantation in both sexes (p < 0.05 in men, and p < 0.005 in women), together with left atrial diameter index (p < 0.01) in women, and mean pulmonary artery pressure (p < 0.001) in men. In conclusion, women with idiopathic dilated cardiomyopathy present a more advanced phase of the disease with greater LV dilation, but do not have a different prognosis.

The spectrum of left ventricular size in dilated cardiomyopathy: Clinical correlates and prognostic implications

To address the issues of variability and prognostic role of left ventricular dimensions in dilated cardiomyopathy (DCM), 144 patients with DCM were studied. They were arbitrarily assigned to two groups according to an echocardiographic left ventricular end-diastolic diameter index < or = 15% (45 patients with mildly dilated cardiomyopathy) and above 15% (99 patients with typically dilated cardiomyopathy) of the upper normality range. Among the patients with mildly dilated cardiomyopathy, there were more men (89% vs 66%; p < 0.01). This group of patients also had a greater prevalence of atrial fibrillation (22% vs 3%; p < 0.001) higher left ventricular fractional shortening (15 +/- 6% vs 13 +/- 5%; p < 0.05), higher ejection fraction (28 +/- 8% vs 24 +/- 8%; p < 0.01), and a lower exercise tolerance (5 +/- 2 MET vs 6 +/- 2 MET; p < 0.05). At the time of follow-up examination (30 +/- 15 months), event-free survival was not significantly different between patients with mildly dilated cardiomyopathy and those with typically dilated cardiomyopathy. Pulmonary capillary wedge pressure (p < 0.001) and left atrial dimension index (p < 0.01) were significant predictors of prognosis as determined by Cox multivariate analysis. Minimal or mild ventricular dilatation is not uncommon in DCM, and it identifies a heterogenous group of patients--some who are in the early stages of disease and others with severe pump dysfunction and persistently small hearts. Ventricular dilatation is not an independent predictor of prognosis.

Predicting heart failure outcome from cardiac and comorbid conditions: The 3C-HF score☆

BACKGROUND Prognostic stratification in heart failure (HF) is crucial to guide clinical management and treatment decision-making. Currently available models to predict HF outcome have multiple limitations. We developed a simple risk stratification model, based on routinely available clinical information including comorbidities, the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause 1-year mortality in HF patients. METHODS We recruited in a cohort study 6274 consecutive HF patients at 24 Cardiology and Internal Medicine Units in Europe. 2016 subjects formed the derivation cohort and 4258 the validation cohort. We entered information on cardiac and comorbid candidate prognostic predictors in a multivariable model to predict 1-year outcome. RESULTS Median age was 69 years, 35.8% were female, 20.6% had a normal ejection fraction, and 65% had at least one comorbidity. During 5861 person-years follow-up, 12.1% of the patients met the study end-point of all-cause death (n=750) or urgent transplantation (n=9). The variables that contributed to outcome prediction, listed in decreasing discriminating ability, were: New York Heart Association class III-IV, left ventricular ejection fraction <20%, no beta-blocker, no renin-angiotensin system inhibitor, severe valve heart disease, atrial fibrillation, diabetes with micro or macroangiopathy, renal dysfunction, anemia, hypertension and older age. The C statistic for 1-year all-cause mortality was 0.87 for the derivation and 0.82 for the validation cohort. CONCLUSIONS The 3C-HF score, based on easy-to-obtain cardiac and comorbid conditions and applicable to the 1-year time span, represents a simple and valuable tool to improve the prognostic stratification of HF patients in daily practice.

Redox state, oxidative stress and endothelial dysfunction in heart failure: the puzzle of nitrate–thiol interaction

Endothelial dysfunction, a critical component in the progression of heart failure, may result from increased oxidative stress, secondary to activation of the adrenergic and the renin–angiotensin systems and to the production of inflammatory cytokines, which in turn contribute to reduced bioavailability of nitric oxide (NO). Oxidative stress, determined by excess production of reactive oxygen species and impairment in the antioxidant defence, is responsible for both the decline of diffusible NO and the decrease in the concentration of essential co-factors of NO synthases. Reactive oxygen species are formed from NO in the presence of oxidants and are involved in the nitration of protein tyrosine residue that can alter protein function. Recent studies re-addressed the impact of nitrate treatment in heart failure in view of the beneficial vascular and cellular effects of NO, and of the discovery of abnormalities in NO pathways in this disease. Concerns exist, however, on the safety of nitrates in this setting. Nitrates stimulate vascular superoxide anion production via activation of NADPH oxidase, and induction of uncoupling of NO synthase. Furthermore, by using donors of sulfhydryl groups, such as cysteine and glutathione, for NO production, nitrates may favour depletion of the intracellular thiol pool, thus impairing the antioxidant defence mechanisms.

Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy

Objective: To assess whether chronic treatment with carvedilol can increase myocardial blood flow (MBF) and MBF reserve in idiopathic dilated cardiomyopathy (IDC). Study design: In a double-blind, placebo-controlled trial, 16 consecutive patients with IDC were randomised to treatment with either carvedilol up to 25 mg twice a day (n = 8, 7 men, mean (SD) age 60 (9) years, mean (SD) left ventricular ejection fraction (LVEF) 30% (5%)), or placebo (n = 8, 6 men, mean (SD) age 62 (9) years, mean (SD) LVEF 28% (6%), NS vs carvedilol group). Before and 6 months after treatment, regional MBF was measured at rest and after intravenous injection of dipyridamole (Dip; 0.56 mg/kg in 4 min) by positron emission tomography and using 13N-ammonia as a flow tracer. Exercise capacity was assessed as the time duration in a maximal bicycle exercise stress test. Results: Carvedilol induced a significant decrease in heart rate at rest and during maximal exercise, and an increase in exercise capacity. Absolute MBF values did not significantly change after carvedilol or placebo treatment, either at rest or during Dip injection, although Dip-MBF tended to improve after treatment. Coronary flow reserve significantly increased following carvedilol treatment (from 1.67 (0.63) to 2.58 (1.04), p<0.001), whereas it remained unchanged following the placebo treatment (from 1.80 (0.84) to 1.77 (0.60), NS). Stress-induced regional perfusion defects decreased after carvedilol treatment (from 38% to 15%). Conclusions: Long-term treatment with carvedilol can significantly increase coronary flow reserve and reduce the occurrence of stress-induced perfusion defects, suggesting a favourable effect of the drug on coronary microvascular function in patients with IDC.

Early expression of pro- and anti-inflammatory cytokines in left ventricular assist device recipients with multiple organ failure syndrome.

To assess whether the combined evaluation of total Sequential Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVAD, we analyzed plasma interleukin (IL)-6, IL-8, IL-10, IL-1ra, IL-1&bgr;, tumor necrosis factor-&agr; (TNF-&agr;), and urine neopterin levels before (day 0) and at 4 hours, 1, 3, 7, 14, and 30 days after LVAD implant in 23 recipients. Eight patients died of MOFS between days 7 and 30 (nonsurvivors). At preimplant, only blood urea nitrogen and age were higher in nonsurvivors than survivors. At 4 hours, IL-8, IL-10, and IL1-ra levels were higher in nonsurvivors than in survivors; t-SOFA was also higher and peaked on day 3 in nonsurvivors. Only IL-8 levels on day 1 were significantly associated with a t-SOFA ≥10 on day 3 (odds ratio 1.10, 95% confidence interval 1.01–1.21, p = 0.04). Neopterin, marker of monocyte activation, increased significantly only in nonsurvivors (p < 0.001). These findings suggest that an activated inflammatory system soon after LVAD implant is implicated in MOFS development. Early monitoring of inflammatory mediators and t-SOFA score may be a valuable tool for outcome prediction in LVAD recipients.

Baseline characteristics of patients recruited in the AREA IN-CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canrenone in Mild Chronic Heart Failure)

Objective Excess aldosterone activity contributes to the pathogenesis and progression of heart failure (HF). Aldosterone antagonists improve clinical outcome in patients with severe HF or left ventricular (LV) dysfunction after myocardial infarction, but knowledge of their impact in mild chronic HF is sparse. AREA IN-CHF was planned to investigate the effects of canrenone on progression of LV remodelling in mild HF. Methods AREA IN-CHF is a multicentre, randomised, double-blind, parallel group comparison of canrenone (up to 50 mg/day) versus placebo in mild stable HF. The primary endpoint is change in echocardiographic LV end-diastolic volume over 12 months. Patients had New York Heart Association class II HF, LV ejection fraction ≤45%, stable standard therapy, creatinine ≤2.5 mg/dl, potassium ≤5.0 mmol/l. Follow-up examinations were scheduled monthly for the first 3 months and every 3 months thereafter. Aldosterone was measured at baseline, brain natriuretic peptide and procollagen type III amino-terminal peptide (PIIINP) at baseline and at 6 months. Echocardiography was performed at baseline, at 6 and 12 months. Results Among 467 patients, median age 64 years (interquartile range (IQR) 56–70 years), 84% were men, 52% had ischaemic HF, 96% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 79% β-blockers. Brain natriuretic peptide, aldosterone and PIIINP were 88 pg/ml (IQR 35–185 pg/ml), 118 pg/ml (IQR 75–177 pg/ml), and 5.38 μg/l (IQR 3.98–7.14 μg/l), respectively. LV end-diastolic volume was 79 ml/m2 (IQR 64–105 ml/m2) and LV ejection fraction was 40% (IQR 33–45%). Conclusions The role of aldosterone blockade in patients with mild HF remains to be established. AREA IN-CHF is addressing this issue in a large population on optimal medical therapy.