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Andrea Di Lenarda

Publications and source records attributed to Andrea Di Lenarda.

At least 19 recordsLinked to original sources
PubMed2006

The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET.

AIMS: Anaemia is a common comorbidity in chronic heart failure (CHF). The predictors of new onset anaemia (NOA) and its long-term prognostic value, particularly in patients treated with beta-blockers, are not known. METHODS AND RESULTS: In COMET, 3029 patients with CHF in NYHA II-IV and EF <35% were randomized to carvedilol or metoprolol tartrate and were followed for an average of 58 months. Plasma haemoglobin (Hb) concentrations were measured at a central laboratory at randomization, at four monthly intervals for the first year and annually thereafter. According to WHO criteria, anaemia was defined when Hb measured <13 g/dL for men and <12 g/dL for women. We considered anaemia to be severe when Hb <11.5 g/dL for men and <10.5 g/dL for women. The baseline mean Hb was 14.2 +/- 1.5 g/dL (n = 2996) and 15.9% of patients had anaemia (males, 16.0%; females, 15.2%). At baseline, severe anaemia was found in 3.3% of patients (males, 3.6%; females, 2.0%). During the study, all-cause mortality (RR 1.47) death or hospitalization (RR 1.28), and heart failure hospitalization (RR 1.43, all P < 0.0001) were higher in anaemic when compared with non-anaemic patients. In patients without anaemia at baseline, at the end of the study, the cumulative frequency of NOA was 28.1% in males and 27.0% in females. NOA increased over time from 14.2% at year 1 to 27.5% at year 5. Predictors of NOA were: higher age, diuretic dose, creatinine (all P < 0.0001), higher serum potassium, lower serum sodium, body mass index, and use of aldosterone antagonists, carvedilol, and digitalis (all P < 0.03). Treatment with carvedilol (vs. metoprolol tartrate) was associated with a 24% increased risk to develop NOA (P = 0.0047), but not severe anaemia (P = 0.18). Patients with a Hb decrease of >3 g/dL (RR 3.37, P < 0.0001) or of 2.0-3.0 g/dL (RR 1.47, P = 0.011) from baseline had an increased subsequent mortality when compared with patients having Hb increases of 0-1.0 g/dL. CONCLUSION: In stable ambulatory CHF patients, development of NOA is frequent and can be predicted by a set of clinical variables. Decreases in Hb over time relate to future increased morbidity and mortality.

Aged↗
PubMed2006

A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the "patient journey") in patients with heart failure: a report from the Carvedilol Or Metoprolol European Trial (COMET).

OBJECTIVES: This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). BACKGROUND: The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials' courses are rarely reported. METHODS: A total of 3,029 patients randomized in the COMET study were included in the analysis. "Patient journey" was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well). RESULTS: Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p < 0.0068). CONCLUSIONS: Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.

Adrenergic beta-Antagonists↗
PubMed2006

Programme to improve the use of beta-blockers for heart failure in the elderly and in those with severe symptoms: results of the BRING-UP 2 Study.

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.

Adrenergic beta-Antagonists↗
PubMed2006

[Italian Network on Congestive Heart Failure: ten-year experience].

IN-CHF is a multicenter registry, designed in 1995 to compile a large clinical database on the epidemiological, clinical characteristics, management and outcomes of heart failure outpatients. Main objectives of IN-CHF registry were to provide cardiological centers with a software to collect data of outpatients during office visit, for educational purpose; and to enter local data into a national registry (IN-CHF registry), for scientific purpose. Entry into the database required a diagnosis of heart failure according to the guidelines of the European Society of Cardiology. The central coordinator of the project was the ANMCO Research Center. The Italian cardiological centers participating in the project are 142, they are well representing the entire country and from March 1995 to July 2005 collected data from 23 855 outpatients. The mean age of the patients was 65+/-13 years and 71.3% were men. Main etiologies were ischemic in 39.4%, hypertensive in 15.8 %, and due to dilated cardiomyopathy in 29%. More than half of the patients (55.3%) had a history of admission for heart failure within the last year; 25.8% of the patients were in NYHA class III-IV, 9.5% showed a heart rate > 100 bpm and 16.5% third heart sound. Left ventricular ejection fraction was severely depressed (< 30%) in 27.6% of the patients, while it was > 40% in 30.9%. Renal dysfunction was present in 3.6% of the patients (serum creatinine level > 2.5 mg/dl), pulmonary disease in 18.7%, diabetes in 16.8% and anemia (hemoglobin < 12 g/dl) in 18.7%. A history of arterial hypertension was common (30.3%); 20.0% and 18.5% of the patients showed atrial fibrillation and left bundle branch block, respectively. Data from our registry provide important insights into clinical and epidemiological characteristics of heart failure outpatients followed in Italian cardiological centers. Starting from this article, every 3 months, the most relevant epidemiological data collected by the IN-CHF investigators will be published.

Aged↗
PubMed2005

Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial.

AIMS: We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy). METHODS AND RESULTS: By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P<0.0001 and RR for SBP>120 mmHg 0.78; 95% CI 0.671-0.907; P<0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P<0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose. CONCLUSION: Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.

Adrenergic beta-Antagonists↗
PubMed2005

Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.

BACKGROUND: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of alphaMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in alphaMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM. METHODS AND RESULTS: A cohort of 434 subjects, 374 (134 affected, 214 unaffected, 26 unknown) belonging to 69 DCM families and 60 (29 affected, 30 unaffected, 1 unknown) in 21 HCM families, was screened for alphaMyHC gene (MYH6) mutations. Three heterozygous MYH6 missense mutations were identified in DCM probands (P830L, A1004S, and E1457K; 4.3% of probands). A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring. All MYH6 mutations were distributed in highly conserved residues, were predicted to change the structure or chemical bonds of alphaMyHC, and were absent in at least 300 control chromosomes from an ethnically similar population. The DCM carrier phenotype was characterized by late onset, whereas the HCM phenotype was characterized by progression toward dilation, left ventricular dysfunction, and refractory heart failure. CONCLUSIONS: This study suggests that mutations in MYH6 may cause a spectrum of phenotypes ranging from DCM to HCM.

Cardiomyopathy, Dilated↗
PubMed2005

Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy.

Thymopoietin or TMPO (indicated by its alternative gene symbol, LAP2, in this work) has been proposed as a candidate disease gene for dilated cardiomyopathy (DCM), since a LAP2 product associates with nucleoplasmic lamins A/C, which are encoded by the DCM gene LMNA. We developed a study to screen for genetic mutations in LAP2 in a large collection of DCM patients and families. A total of 113 subjects from 88 families (56 with familial DCM (FDC) and 32 with sporadic DCM) were screened for LAP2 mutations using denaturing high-performance liquid chromatography and sequence analysis. We found a single putative mutation affecting the LAP2alpha isoform in one FDC pedigree. The mutation predicts an Arg690Cys substitution (c.2068C>T; p.R690C) located in the C-terminal domain of the LAP2alpha protein, a region that is known to interact with lamin A/C. RT-PCR, Western blot analyses, and immunolocalization revealed low-level LAP2alpha expression in adult cardiac muscle, and localization to a subset of nuclei. Mutated Arg690Cys LAP2alpha expressed in HeLa cells localized to the nucleoplasm like wild-type LAP2alpha, with no effect on peripheral and nucleoplasmic lamin A distribution. However, the in vitro interaction of mutated LAP2alpha with the pre-lamin A C-terminus was significantly compromised compared to the wild-type protein. LAP2 mutations may represent a rare cause of DCM. The Arg690Cys mutation altered the observed LAP2alpha interaction with A-type lamins. Our finding implicates a novel nuclear lamina-associated protein in the pathogenesis of genetic forms of dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed2005

Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET.

BACKGROUND: Beta-blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the beta1-blocker metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol. METHODS: In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy. RESULTS: A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups. CONCLUSION: Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.

Adrenergic beta-Antagonists↗
PubMed2005

Exchange of beta-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial).

BACKGROUND: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta1-, beta2- and alpha1-blocker, vs. metoprolol tartrate, a beta1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol. AIM: To investigate the safety and tolerability of switching beta-blockers in CHF. METHODS: At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label beta-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days. RESULTS: 1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second beta-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from beta-blockade. CONCLUSION: Our data show that switching beta-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.

Adrenergic beta-Antagonists↗
PubMed2005

Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure.

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.

Aged↗
PubMed2005

Prognostic role of non-sustained ventricular tachycardia in a large cohort of patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The identification of patients with idiopathic dilated cardiomyopathy (IDC) at higher risk of sudden death (SD) is still an unsolved issue, and the role of non-sustained ventricular tachycardia (NSVT) uncertain. METHODS: The effect of NSVT on total mortality, SD and life-threatening arrhythmias was evaluated in 554 patients with IDC on optimal medical treatment and at long-term follow-up (81 +/- 58 months). RESULTS: At diagnosis, 240 patients (43%) had NSVT at Holter monitoring and 314 (57%) did not. During follow-up, 189 patients (5/100 patients-year) died or underwent heart transplantation; SD occurred in 53 patients (1.4/100 patients-year); SD + non-fatal ventricular arrhythmias occurred in 75 patients (2/100 patients-year). Patients with and without NSVT at diagnosis had the same 5-year transplant-free survival rate (76 vs 76%, p = NS) and a similar incidence of SD (10 vs 7%, p = NS). The length and rate of NSVT did not show any significant relationship with the outcome. Only heart failure symptoms (NYHA class III-IV) (hazard ratio [HR] 1.9, p = 0.015) and severe left ventricular impairment (left ventricular ejection fraction < or = 0.30 and left ventricular end-diastolic diameter > or = 70 mm) (HR 2.7, p < 0.0001) were independently associated with higher SD risk. At multivariate analysis the presence of frequent NSVT episodes (> or = 3 runs/day) was associated with an increased risk of total mortality (HR 1.68, p = 0.041) and of major ventricular arrhythmias (HR 2.11, p = 0.037), but only in the subgroup of patients with severe left ventricular impairment. CONCLUSIONS: Patients with advanced heart failure symptoms, severe left ventricular dysfunction and dilation had a higher risk of SD independently of NSVT. The finding of more frequent NSVT was associated with an increased risk of all-cause mortality and of major ventricular arrhythmias in patients with severe left ventricular impairment.

Adult↗
PubMed2004

The role of implantable cardioverter defibrillator for primary vs secondary prevention of sudden death in patients with idiopathic dilated cardiomyopathy.

AIM: To analyse the characteristics and outcome of patients with idiopathic dilated cardiomyopathy (DC) considered at high risk of sudden death (SD) and treated with implantable cardioverter defibrillators (ICD) for primary prevention (Group A) in comparison with patients treated with ICDs because of previous sustained ventricular tachyarrhythmias or syncope (Group B). METHODS: Group A consisted of 27 patients with at least two of the following criteria: left ventricular end-diastolic diameter (LVEDD) > or =70 mm (74%), LV ejection fraction (LVEF) < or =30% (78%), non-sustained ventricular tachycardia (VT) (56%), long history of disease (> or =48 months since diagnosis, 85%) and family history of SD (11%). Group B consisted of 27 patients treated with ICDs because of sustained VT/fibrillation (n=18) or syncope (n=9). RESULTS: NYHA class, LVEF, LVEDD and amiodarone treatment were similar in the two groups. Patients in group A were younger (46+/-15 vs 59+/-17 years, P=0.0008), were more often treated with beta-blockers (89% vs 62%; P=0.02) and had a longer interval since diagnosis (86+/-60 vs 40+/-50 months; P=0.004). Twelve month rates of appropriate intervention (AI) were 41% in Group A and 57% in group B (P NS). In group A, after a mean follow-up of 21+/-14 months, patients showing the combination of LVEF < or =30% and LVEDD > or =70 mm had the highest frequency of AI (76% vs 10%, P=0.005). In group B, after a mean follow-up of 33+/-23 months, 78% of patients with syncope had AI. Total and sudden deaths were 11% and 4% in group A and 19% and 4% in group B (P NS). CONCLUSIONS: Patients with idiopathic DC treated with ICD for primary prevention because they were considered at high risk of SD according to clinical criteria showed a high rate of AI, similar to that of patients treated for secondary prevention. The highest rate of AI was seen in patients with both severe dysfunction and dilatation and in those with previous syncope.

Adrenergic beta-Antagonists↗
PubMed2004

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

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

Adrenergic beta-Antagonists↗
PubMed2004

Long-term oral carvedilol in chronic heart failure.

The long-term beta-blockade strategy with carvedilol, metoprolol succinate or bisoprolol is now strongly recommended to reduce the rates of mortality and morbidity in patients with chronic heart failure (CHF). Although the benefits observed with such drugs are viewed as a class effect, theoretically, carvedilol might be superior to the other two agents, considering its unique pharmacological profile, which includes a more comprehensive antiadrenergic activity and potentially relevant ancillary properties. So far, carvedilol has been proven to be effective and safe in a broader range of CHF patients than metoprolol and bisoprolol. Moreover, a recent large clinical trial has shown a significantly greater survival benefit with carvedilol as directly compared with metoprolol tartrate. Therefore, carvedilol may be the preferred beta-blocking agent to treat patients with CHF.

Administration, Oral↗
PubMed2004

[How the natural history of dilated cardiomyopathy has changed. Review of the Registry of Myocardial Diseases of Trieste].

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers. However, a strong heterogeneity of prognosis was observed among patients both in familial and sporadic cases. Early diagnosis and treatment allowed to recognize two distinct subgroups, one with a rapidly progressive downhill course, high mortality and urgent indication to heart transplantation, another with a more favorable outcome. Long-term optimized treatment with ACE-inhibitors (in 90% of cases) and beta-blockers (in 87% of cases) was associated with a remarkable clinical improvement in 50% of patients and apparent "healing" in 16% of cases. A systematic and accurate echocardiographic follow-up showed in these cases a significant improvement of the left ventricular ejection fraction (LVEF) with "reverse remodeling", frequently associated with a decrease of severity of functional mitral regurgitation and regression of the restrictive filling pattern. The response to optimal treatment showed a strong relation to long-term outcome. The 8-year transplant-free survival, starting from the evaluation at 2 years, was 31% in patients with persistent NYHA class III-IV, 64% in NYHA class I-II and LVEF < or = 40%, 83% in NYHA class I-II and LVEF > 40% and 94% in patients with apparent "healing" (p < 0.0001). Long-term follow-up showed a significant clinical progression of the disease in 33% of cases, independently of the initial clinical response to treatment. Predictive factors of a favorable response to beta-blocker treatment associated with ACE-inhibitors were a history of mild hypertension, an early diagnosis and treatment and the presence of sinus tachycardia. The risk of sudden death was increased particularly in patients with long-term persistent or progressive left ventricular dilation and dysfunction. A rigorous pharmacological approach (optimization of beta-blockers, withdrawal or decrease of dosage of digitalis), and selective non-pharmacological strategy (automated implantable cardioverter-defibrillators for primary prevention in high-risk patients) are potentially effective to decrease the incidence of sudden death during long-term follow-up. In conclusion, the Heart Muscle Disease Registry of Trieste gave us in the last 25 years new insights into the natural history of DCM, underlying the importance of a rigorous and systematic approach both at clinical presentation and during long-term follow-up on optimized medical treatment.

Arrhythmias, Cardiac↗