Assessment of myocardial deformation with cardiac magnetic resonance strain imaging improves risk stratification in patients with dilated cardiomyopathy.

AIMS: To investigate the prognostic impact of left-ventricular (LV) cardiac magnetic resonance (CMR) deformation imaging in patients with non-ischaemic dilated cardiomyopathy (DCM) compared with late-gadolinium enhancement (LGE) quantification and LV ejection fraction (EF). METHODS AND RESULTS: A total of 210 subjects with DCM were examined prospectively with standard CMR including measurement of LGE for quantification of myocardial fibrosis and feature tracking strain imaging for assessment of LV deformation. The predefined primary endpoint, a combination of cardiac death, heart transplantation, and aborted sudden cardiac death, occurred in 26 subjects during the median follow-up period of 5.3 years. LV radial, circumferential, and longitudinal strains were significantly associated with outcome. Using separate multivariate analysis models, global longitudinal strain (average of peak negative strain values) and mean longitudinal strain (negative peak of the mean curve of all segments) were independent prognostic parameters surpassing the value of global and mean LV radial and circumferential strain, as well as NT-proBNP, EF, and LGE mass. A global longitudinal strain greater than -12.5% predicted outcome even in patients with EF < 35% (P < 0.01) and in those with presence of LGE (P < 0.001). Mean longitudinal strain was further investigated using a clinical model with predefined cut-offs (EF < 35%, presence of LGE, NYHA class, mean longitudinal strain greater than -10%). Mean longitudinal strain exhibited an independent prognostic value surpassing that provided by NYHA, EF, and LGE (HR = 5.4, P < 0.01). CONCLUSION: LV longitudinal strain assessed with CMR is an independent predictor of survival in DCM and offers incremental information for risk stratification beyond clinical parameters, biomarker, and standard CMR.

Longitudinal quantile regression in the presence of informative dropout through longitudinal-survival joint modeling.

We propose a joint model for a time-to-event outcome and a quantile of a continuous response repeatedly measured over time. The quantile and survival processes are associated via shared latent and manifest variables. Our joint model provides a flexible approach to handle informative dropout in quantile regression. A Monte Carlo expectation maximization strategy based on importance sampling is proposed, which is directly applicable under any distributional assumption for the longitudinal outcome and random effects. We consider both parametric and nonparametric assumptions for the baseline hazard. We illustrate through a simulation study and an application to an original data set about dilated cardiomyopathies.

Clinical utility and prognostic value of left atrial volume assessment by cardiovascular magnetic resonance in non-ischaemic dilated cardiomyopathy.

AIMS: Echocardiographic studies have shown that left atrial volume (LAV) predicts adverse outcome in small heart failure (HF) cohorts of mixed aetiology. However, the prognostic value of LAV in non-ischaemic dilated cardiomyopathy (DCM) is unknown. Cardiovascular magnetic resonance (CMR) allows accurate and reproducible measurement of LAV. We sought to determine the long-term prognostic significance of LAV assessed by CMR in DCM. METHODS AND RESULTS: We measured LAV indexed to body surface area (LAVi) in 483 consecutive DCM patients referred for CMR. Patients were prospectively followed up for a primary endpoint of all-cause mortality or cardiac transplantation. During a median follow-up of 5.3 years, 75 patients died and 9 underwent cardiac transplantation. After adjustment for established risk factors, LAVi was an independent predictor of the primary endpoint [hazard ratio (HR) per 10 mL/m(2) 1.08; 95% confidence interval (CI) 1.01-1.15; P = 0.022]. LAVi was also independently associated with the secondary composite endpoints of cardiovascular mortality or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.19; P = 0.003), and HF death, HF hospitalization, or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.18; P = 0.001). The optimal LAVi cut-off value for predicting the primary endpoint was 72 mL/m(2). Patients with LAVi >72 mL/m(2) had a three-fold elevated risk of death or transplantation (HR 3.00; 95% CI 1.92-4.70; P < 0.001). LAVi provided incremental prognostic value for the prediction of transplant-free survival (net reclassification improvement 0.17; 95% CI 0.05-0.29; P = 0.002). CONCLUSIONS: LAVi is a powerful independent predictor of transplant-free survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis.

AIMS: It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. METHODS AND RESULTS: A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. CONCLUSION: Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.

Sex and gender differences in myocarditis and dilated cardiomyopathy.

Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is, in turn, a major cause of acute DCM in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of DCM differ between the sexes. This seminar provides a contemporary perspective on the immune mediators of myocarditis, including interdependent elements of the innate and adaptive immune response. The heart's acute response to injury is influenced by sex hormones that appear to determine the subsequent risk of chronic DCM. Preliminary data suggest additional genetic variations may account for some of the differences in epidemiology, left ventricular recovery, and survival between men and women. We highlight the gaps in our knowledge regarding the management of women with acute DCM and discuss emerging therapies, including bromocriptine for the treatment of peripartum cardiomyopathy.

Copeptin in the assessment of acute lung injury and cardiogenic pulmonary edema.

BACKGROUNDS: Copeptin has been studied as an excellent predictor of outcome in a variety of diseases, its value is even superior to that of B-type natriuretic peptide (BNP) in heart failure, but little is known about its characteristics in acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). We sought to assess the diagnostic and prognostic value of copeptin together with N-terminal pro-BNP (NT-proBNP) in patients with ARDS/ALI or cardiogenic pulmonary edema (CPE). METHODS: Measurement of copeptin and NT-proBNP levels in plasma from 121 consecutive patients with either ARDS/ALI or CPE enrolled in a prospective single center study. RESULTS: In a derivation cohort of 87 patients with ARDS/ALI and 34 patients with CPE, a copeptin threshold of >40.11 pmol/L provided a specificity of 88.2% and a sensitivity of 60.9% for the diagnosis of ARDS/ALI, a NT-proBNP cut point of <2813 pg/ml had a specificity of 79.4% and sensitivity of 65.5% for it. Multivariate Cox regression analysis showed that copeptin was the strongest predictor for mortality in patients with ARDS/ALI [hazard ratio (HR) = 4.72, P < 0.001] and CPE (HR = 3.52, P = 0.019), the association between increasing copeptin and death was statistically significant in patients with ARDS/ALI (HR = 2.64, P = 0.035) and patients with CPE (HR = 1.62, P = 0.029). CONCLUSION: Copeptin of >40.11 pmol/L had a high specificity for the diagnosis of ARDS/ALI in patients presenting with ARDS/ALI or CPE. Compared to NT-proBNP, copeptin was a stronger prognostic marker for short-term mortality.

Feasibility of semi-quantitative assessment of left ventricular contractile reserve in dilated cardiomyopathy.

BACKGROUND: We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high-dose dobutamine stress-echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy. PURPOSE: To assess the feasibility of semi-quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy. METHODS: High-dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi-quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine-induced change was ≥5%. RESULTS: Twenty-seven (45.8%) patients died during the 5-year follow-up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed semi-quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi-quantitative assessment of LV contractile reserve. CONCLUSIONS: Our data indicate that semi-quantitative assessment of LV contractile reserve is feasible by differently skilled operators.

Prognostic value of pulsed tissue Doppler imaging for the assessment of left ventricular systolic function in patients with nonischemic dilated cardiomyopathy.

There is still some debate regarding the prognostic significance of left ventricular longitudinal systolic dysfunction as assessed by tissue Doppler (TD) imaging in patients with chronic heart failure (HF), since previous studies have included patients with postischemic wall motion abnormalities. Thus, this study was designed to ascertain whether TD-derived longitudinal systolic dysfunction may influence the outcome of patients with nonischemic chronic HF. In 200 consecutive patients with chronic HF secondary to dilated cardiomyopathy and no history of ischemic heart disease, peak systolic mitral annular velocity (S(m) ) was measured by pulsed TD at the septal and lateral annular sites. The end points were cardiac death or hospitalization for worsening HF. Mean follow-up duration was 30 months. In a time independent analysis, averaged S(m) calculated as the average of septal and lateral S(m) , resulted to be a significant predictor of outcome in the study population (area under receiver-operator characteristic curve: cardiovascular death, 0.69, P < 0.0001; cardiovascular events, 0.64, P = 0.0005). In a time-dependent analysis, average S(m) was associated with both cardiovascular death (hazard ratio 0.832, P = 0.0019) and cardiovascular events (hazard ratio 0.904, P = 0.039), independently of other clinical risk factors and echocardiographic parameters of systolic function. Septal S(m) but not lateral S(m) was independently associated with the outcome measures. In conclusion, the assessment of systolic mitral annular velocity by pulsed TD is a useful indicator for prognostic stratification of patients with nonischemic dilated cardiomyopathy and chronic HF.

The impact of left ventricular size on response to cardiac resynchronization therapy.

UNLABELLED: Patients with nondilated (NDCM) or severely dilated cardiomyopathies (SDCM) have been underrepresented in clinical trials of cardiac resynchronization therapy (CRT). We examined changes in left ventricular ejection fraction (LVEF) and survival in patients with NDCM or SDCM compared with those with traditionally studied moderately dilated cardiomyopathy. METHODS: We evaluated 800 consecutive patients undergoing the original implantation of a biventricular pacemaker between January 2004 and August 2007. For inclusion, patients had a baseline and pre-CRT echocardiogram, an LVEF ≤40%, a US social security number, and New York Heart Association class II to IV symptoms on standard medical therapy. Patients with a follow-up echocardiogram >2 months after device implantation were included in an analysis of remodeling. Using multivariate models, the impact of baseline left ventricular end-diastolic diameter (LVEDD) on change in LVEF and all-cause mortality was assessed. RESULTS: A total of 668 patients met inclusion criteria and were included in the assessment of mortality. Four hundred seventy-one had an appropriately timed follow-up echocardiogram and were included in the analysis of remodeling. Patients in all 3 groups realized improvements in LVEF (%) after CRT as follows: NDCM (n = 137; LVEDD ≤5.5 cm) 10.0 ± 12.7, P < .001; moderately dilated cardiomyopathy (n = 233; LVEDD 5.6-6.9 cm) 8.2 ± 11.3, P < .001; and SDCM (n = 101; LVEDD ≥7.0 cm) 5.4 ± 9.4, P < .001. In multivariate analysis, baseline LVEDD was inversely associated with change in LVEF (parameter estimate -3.13 ± 0.56, P < .001) and directly associated with increased all-cause mortality (hazard ratio 1.25 [1.05-1.47] P = .01). CONCLUSION: Patients with NDCM and SDCM experience significant improvements in LVEF after CRT. The degree of baseline left ventricular dilatation before CRT is an important predictor of subsequent changes in LVEF and survival.

Association of left ventricular dilation at listing for heart transplant with postlisting and early posttransplant mortality in children with dilated cardiomyopathy.

BACKGROUND: In patients with dilated cardiomyopathy, the magnitude of cardiac remodeling often correlates with the clinical severity of heart failure. We sought to determine whether measures of left ventricular (LV) dilation and systolic dysfunction in children with dilated cardiomyopathy at the time of listing for cardiac transplantation are associated with survival while waiting for and early after transplant. METHODS AND RESULTS: We analyzed echocardiographic data obtained within 6 months of listing for heart transplant and clinical data from 261 children with dilated cardiomyopathy who were included in both the Pediatric Cardiomyopathy Registry and the Pediatric Heart Transplant Study. Median time to listing after diagnosis was 1.9 months and to transplant after listing was 0.8 months. There were 42 deaths (29 waiting and 13 within 6 months after transplant). We found a significant age-dependent association of LV end-diastolic dimension z score (n=204, 31 deaths) with death controlling for race, transplant status, and medical insurance. The association was strongest for infants younger than 6 months at diagnosis (hazard ratio 1.47, P=0.008) and was not significant in children older than 5 years at diagnosis. A similar interaction was identified between age and LV end-systolic dimension z score (P=0.04). Neither LV function nor mass was associated with death, overall, or in subgroups. CONCLUSIONS: The severity of LV dilation at listing for heart transplant is associated with outcome in infants and young children with dilated cardiomyopathy, whereas the severity of LV systolic dysfunction is not. These findings should be considered in risk stratification of these children at listing.

Relative survival in dilated cardiomyopathy: a stratification study of long-term outcome to evaluate life insurance cover.

OBJECTIVES: The aim of this study was to compare mortality of dilated cardiomyopathy (DCM) patients with the mortality in the background Italian population, taking into account demographic characteristics and clinical stratification of long-term outcome, ie, "reverse remodelling" within the first 2 years of follow-up. BACKGROUND: DCM is a myocardial disease, characterized by left and/or right ventricular dilation and dysfunction and poor outcome. Evidence-based treatment with ACE inhibitors, beta-blockers and, in the last decade, implantable cardioverter defibrillators have been demonstrated to improve significantly heart failure symptoms and prognosis. At present, DCM patients are unlikely to be accepted for life insurance. METHODS: A cohort of 577 DCM patients consecutively enrolled from 1988 to 2004 in the Heart Muscle Disease Registry of Trieste, Italy, was matched by sex, age and registry data entry with the mortality data of the Italian population. Relative survival has been estimated by means of Kaplan-Meier technique, and mortality ratios (MR) with corresponding 95% confidence intervals have been computed. RESULTS: DCM patients who showed a significant reverse remodelling within the first 2 years of treatment showed comparable survival with respect to the control population, and therefore could be taken into consideration for life insurance coverage, at least for a short or medium-term of years. CONCLUSIONS: The data illustrate that survival probability strongly depend on the individual treatment and evolution of the disease and could be easily measured within the first 2 years of follow-up. If this information is collected at the time of evaluation of an applicant for life cover, the insurance company could possibly improve its risk stratification.

Prognostic utility of B-type natriuretic peptide assessment in stable low-risk outpatients with nonischemic cardiomyopathy after decompensated heart failure.

OBJECTIVES: We investigated the clinical utility of B-type natriuretic peptide (BNP) assay in stable outpatients with nonischemic dilated cardiomyopathy (NICM) after decompensated heart failure (HF). BACKGROUND: Patients with NICM admitted for decompensated HF frequently experience sudden death or redecompensation after hospital discharge. The prognostic value of BNP during hospitalization has been demonstrated. However, clinical utility of BNP in stable outpatient setting has been poorly investigated. METHODS: Eighty-three NICM outpatients who were clinically stable in New York Heart Association functional class 1 to 2 for 6 months after discharge for decompensated HF were enrolled, and then followed for an additional 18 months. The main end point was first readmission for decompensated HF or death. B-type natriuretic peptide levels were measured at 3-month intervals from discharge to enrollment, and echocardiographic dimensions at discharge and enrollment. RESULTS: Mean discharge BNP level was 210 +/- 148 pg/ml. Twenty-eight patients were readmitted for decompensated HF or suddenly died at a median time of 11 months from the time of discharge. Among various variables including BNP measurements, clinical parameters and echocardiographic dimensions, a 6-month post-discharge BNP of >190 pg/ml was most closely associated with combined event in the Cox proportional hazards model (hazard ratio 2.29; 95% confidence interval 1.42 to 3.56; p = 0.0005), and had the best discriminatory power (area under the receiver operating characteristic curve 0.91, sensitivity 96%; specificity 76%). CONCLUSIONS: Even in stable low-risk outpatients with NICM at 6 months after hospital discharge for decompensated HF, BNP assessment predicts a long-term risk of redecompensation.

The impact of left ventricular reconstruction on survival in patients with ischemic cardiomyopathy.

OBJECTIVE: Left ventricular reconstruction (LVR) is performed to improve the morphologic structure and function of the heart in patients with heart failure. This procedure has been performed at the Cleveland Clinic Foundation since 1997. We assessed mortality, functional status, and predictors of outcome in these patients. METHODS: Data were extracted from multiple prospectively acquired datasets on demographic, clinical, and operative details of 220 consecutive patients who underwent LVR between July 1997 and July 2003, where the indication for surgery was heart failure (of whom 66% had New York Heart Association (NYHA) functional class III or IV symptoms). Mortality, functional status, and postoperative complications were ascertained by reference to the clinical record, social security death index, and by phone contact. Mean preoperative left ventricular ejection fraction (LVEF) was 21.5+/-7.3% and mean left ventricular end-diastolic diameter was 6.4+/-1.0 cm. The mean age was 61.4+/-9.0 years and 80% were male. The majority (86%) of patients underwent concomitant coronary artery bypass grafting and 49% underwent mitral valve surgery. RESULTS: Thirty-day mortality was 1% and survival at 1, 3, and 5 years was 92%, 90%, and 80%, respectively. Of the survivors for whom data on NYHA functional class were available, 85% were in NYHA functional class I or II. Mortality was predicted by reduced preoperative ejection fraction <20% (unadjusted hazard ratio 1.53, p = 0.02), body mass index < or = 24 kg/m2 (unadjusted hazard ratio 1.69, p = 0.01), QRS duration > or = 130 ms (unadjusted hazard ratio 1.66, p = 0.01) and the requirement for renal replacement therapy postoperatively (unadjusted hazard ratio 3.85, p < 0.01). Mean LVEF improved to 24.7+/-8.86% (p < 0.01) and left ventricular volumes were also significantly reduced. CONCLUSIONS: In selected patients with heart failure, LVR, in conjunction with revascularization and valve surgery, is associated with excellent survival, improved symptoms, and improved LVEF and left ventricular dimensions.

Preserved heart rate variability identifies low-risk patients with nonischemic dilated cardiomyopathy: results from the DEFINITE trial.

BACKGROUND: The recent expansion of indications for prophylactic implantable cardioverter-defibrillator (ICD) placement in subjects with nonischemic dilated cardiomyopathy has raised concerns about the cost-effectiveness of this therapy. OBJECTIVES: The purpose of this study was to identify low-risk patients with nonischemic dilated cardiomyopathy who may not require prophylactic ICD placement. METHODS: This was a prospective study of 274 participants in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a randomized controlled trial that evaluated the role of prophylactic ICD placement in patients with nonischemic dilated cardiomyopathy. The patients underwent 24-hour Holter recording for analysis of heart rate variability (HRV). The primary HRV variable was the standard deviation of normal R-R intervals (SDNN). Patients with atrial fibrillation and frequent ventricular ectopy (>25% of beats) were excluded from HRV analysis (23% of patients). SDNN was categorized in tertiles, and Kaplan-Meier analysis was performed to compare survival in the three tertiles and excluded patients. RESULTS: The study population was 73% male, with a mean age of 59 +/- 12 years and mean left ventricular ejection fraction of 21% +/- 6%. After 3-year follow-up, significant differences in mortality rates were observed: SDNN >113 ms: 0 (0%), SDNN 81-113 ms: 5 (7%), SDNN <81 ms: 7 (10%), excluded patients: 11 (17%) (P = .03). There were no deaths in the tertile with SDNN >113 ms regardless of treatment assignment (ICD vs control). CONCLUSION: Patients with nonischemic dilated cardiomyopathy and preserved HRV have an excellent prognosis and may not benefit from prophylactic ICD placement. Patients with severely depressed HRV and patients who are excluded from HRV analysis because of atrial fibrillation and frequent ventricular ectopy have the highest mortality.

Economic evaluation and survival analysis of immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (DCM) is a life-threatening heart disease and a major reason for heart transplantations. The medical efficacy of immunoadsorption (IA) for DCM patients has been demonstrated in initial clinical studies. This prospective matched-case control study examined 5-year survival rates, direct medical costs, and cost-effectiveness in Germany (n=34) from a health-care system perspective. In a cost-effectiveness analysis costs per life year gained were calculated. Patients treated with IA showed a greater survival rate: 5-year survival rate in the intervention group was 82% vs. 41% in controls. Log rank statistics after Kaplan-Meier analysis of cumulated survival probability were highly significant. Initial intervention costs for IA were found to be 28,400 euro per patient treated. Direct medical costs for a 5-year follow-up were 128,600 euro per patient treated with IA and 75,500 euro in controls. Considering only the actual survival time we calculated annual treatment costs of 24,900 euro in the IA group and 28,900 euro in controls. The cost-effectiveness ratio expressed in costs per life year gained was 34,400 euro. This is the first controlled study to perform 5-year survival analysis and economic evaluation of this new emerging technology for patients with DCM. Although high initial treatment costs for IA are incurred, the significantly better survival rates lead to reasonable costs per live year gained.

Noninvasive assessment of cardiac mechanics and clinical outcome after partial left ventriculectomy.

BACKGROUND: Partial left ventriculectomy (PLV) was developed as a therapy for end-stage heart failure, but results were variable with few a priori predictors of outcome. Little is known about its effects on myocardial mechanics and their relation to clinical outcome. METHODS: Twenty-four dilated cardiomyopathy patients underwent cardiac magnetic resonance imaging (MRI) before PLV, and 3 and 12 months after surgery. Left ventricular (LV) circumferential shortening and wall stress were computed at three short-axis levels. Exploratory outcome analysis grouped patients according to the timing of adverse cardiac events postsurgery. RESULTS: LV mass and volume were decreased at each postsurgical time point (all p < 0.01). At 3 months, regional wall stress was reduced at all short-axis levels; but by 12 months stress was reduced from baseline only at the apex. Circumferential shortening was increased significantly at both postsurgical time points at each level. On average, septal shortening was negative (stretching) before surgery, but increased significantly, and was positive, postsurgery. Exploratory outcome analysis found that negative values of basal septum circumferential shortening before surgery increased the probability of event-free survival beyond 6 months. CONCLUSIONS: Regional heterogeneity of LV myocardial function, associated with dilated cardiomyopathy, was diminished after PLV but was also related to patient outcome. MRI with tissue tagging is useful for assessing the efficacy of surgical therapies for congestive heart failure.

Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT.

OBJECTIVES: The purpose of this multicenter randomized trial was to compare total mortality during therapy with amiodarone or an implantable cardioverter-defibrillator (ICD) in patients with nonischemic dilated cardiomyopathy (NIDCM) and nonsustained ventricular tachycardia (NSVT). BACKGROUND: Whether an ICD reduces mortality more than amiodarone in patients with NIDCM and NSVT is unknown. METHODS: One hundred three patients with NIDCM, left ventricular ejection fraction < or =0.35, and asymptomatic NSVT were randomized to receive either amiodarone or an ICD. The primary end point was total mortality. Secondary end points included arrhythmia-free survival, quality of life, and costs. RESULTS: The study was stopped when the prospective stopping rule for futility was reached. The percent of patients surviving at one year (90% vs. 96%) and three years (88% vs. 87%) in the amiodarone and ICD groups, respectively, were not statistically different (p = 0.8). Quality of life was also similar with each therapy (p = NS). There was a trend with amiodarone, as compared to the ICD, towards improved arrhythmia-free survival (p = 0.1) and lower costs during the first year of therapy ($8,879 US dollars vs. $22,039 US dollars, p = 0.1). CONCLUSIONS: Mortality and quality of life in patients with NIDCM and NSVT treated with amiodarone or an ICD are not statistically different. There is a trend towards a more beneficial cost profile and improved arrhythmia-free survival with amiodarone therapy.

Prognostic value of serial cardiac assessment and familial screening in patients with dilated cardiomyopathy.

OBJECTIVES: This prospective study was performed to analyse whether routine clinical follow-up investigations at 12+/-6 months add to risk stratification and improve survival rates in patients with a first diagnosis of dilated cardiomyopathy (DCM). METHODS: Four hundred and eighty consecutive patients (mean age 53.4+/-12.3 years, 369 males, mean NYHA class 2.4+/-0.8) with invasively confirmed DCM were included and followed for 3.9+/-3.5 years. Patients were requested to adhere to a follow up investigation within 6-18 months either at the referring physicians or at our out patient department. Two hundred and eighty-one of the 480 patients presented for follow up which consisted of a detailed evaluation of symptoms, standardized physical examination, 12-lead-electrocardiogram recording and echocardiography. Seventeen patients were lost for follow up, 182 did not seek specialized medical follow up. Patients outcome was assessed by structured telephone interviews. RESULTS: Independent predictors of death or transplantation at initial diagnosis were LV-ejection fraction <30% (P=0.0001, risk ratio 2.25), LV-end diastolic pressure >or=15 mmHg (P=0.002, risk ratio 2.0), age >or=54 years, (P=0.04, risk ratio 1.55), and presence of left bundle branch block (P=0.046, risk ratio 1.53). On follow up investigations only deterioration of clinical status by at least one NYHA-class (P=0.001, risk ratio 2.6) and new onset or worsening of mitral regurgitation (P=0.02, risk ratio 1.8), remained independent prognostic factors for cardiac death. Patients who presented for routine follow up revealed significant better 5-year survival rates (n=281, 70%) than those who did not (n=153, 55%, P=0.005). CONCLUSIONS: Routine clinical follow up investigations within 6-18 months after first diagnosis of DCM adds to risk stratification and improves survival rates.

DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE).

The DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) was a multi-center, randomized, investigator-initiated trial. Patients enrolled in the trial had non-ischemic cardiomyopathy (LVEF 10 PVCs/hr or non-sustained ventricular tachycardia defined as 3 to 15 beats at a rate of >120 bpm) on Holter monitor or telemetry within the past 6 months. All patients received standard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and beta-blockers. Patients were randomized to implantable cardioverter defibrillator (ICD) versus no ICD. Patients were followed for 2 to 3 years. The primary endpoint was total mortality. Quality of life and pharmacoeconomics analysis was also performed. A registry tracked patients who met basic inclusion criteria but were not randomized. We estimated an annual total mortality of 15% at 2 years in the treatment arm that did not receive an ICD. The ICD was expected to reduce mortality by 50%. Approximately 229 patients were required in each treatment group. Forty-five centers were included in this trial that was designed to last an estimated 4 years. Enrollment was projected to occur over 2 1/2 years with a post enrollment follow-up of 1 1/2 years.