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Circulation | 2014
Raymond H. Chan; Barry J. Maron; Iacopo Olivotto; Michael J. Pencina; Gabriele Egidy Assenza; Tammy S. Haas; John R. Lesser; Christiane Gruner; Andrew M. Crean; Harry Rakowski; James E. Udelson; Ethan J. Rowin; Massimo Lombardi; Franco Cecchi; Benedetta Tomberli; Paolo Spirito; Francesco Formisano; Elena Biagini; Claudio Rapezzi; Carlo N. De Cecco; Camillo Autore; E. Francis Cook; Susie N. Hong; C. Michael Gibson; Warren J. Manning; Evan Appelbaum; Martin S. Maron
Background— Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. Methods and Results— We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3–38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). Conclusions— Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.
Circulation | 2009
Claudio Rapezzi; Giampaolo Merlini; Candida Cristina Quarta; Letizia Riva; Simone Longhi; Ornella Leone; Fabrizio Salvi; Paolo Ciliberti; Francesca Pastorelli; Elena Biagini; Fabio Coccolo; Robin M. T. Cooke; Letizia Bacchi-Reggiani; Diego Sangiorgi; Alessandra Ferlini; Michele Cavo; Elena Zamagni; Maria Luisa Fonte; Giovanni Palladini; Francesco Salinaro; Francesco Musca; Laura Obici; Angelo Branzi; Stefano Perlini
Background— Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis. Methods and Results— We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1±0.5 versus 0.9±0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events. Conclusions— AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.
Circulation | 2009
Paolo Spirito; Camillo Autore; Claudio Rapezzi; Paola Bernabò; Roberto Badagliacca; Martin S. Maron; Sergio Bongioanni; Fabio Coccolo; N.A. Mark Estes; Caterina Stella Barillà; Elena Biagini; Giovanni Quarta; Maria Rosa Conte; Paolo Bruzzi; Barry J. Maron
Background— The prognostic significance of syncope has not been investigated systematically in hypertrophic cardiomyopathy, and treatment strategies have been based largely on intuition and experience. Methods and Results— We assessed the relationship between syncope and sudden death in 1511 consecutive patients with hypertrophic cardiomyopathy. Unexplained (n=153) or neurally mediated (n=52) syncope occurred in 205 patients (14%). Over a 5.6±5.2-year follow-up, 74 patients died suddenly. Relative risk of sudden death was 1.78 (95% confidence interval 0.88 to 3.51, P=0.08) in patients with unexplained syncope and 0.91 (95% confidence interval 0.00 to 3.83, P=1.0) in those with neurally mediated syncope compared with patients without syncope. In multivariable analysis, the temporal proximity of unexplained syncope to initial patient evaluation was independently associated with risk of sudden death (P=0.006). Patients with unexplained syncope within 6 months before the initial evaluation showed a 5-fold increase in risk compared with patients without syncope (adjusted hazard ratio 4.89, 95% confidence interval 2.19 to 10.94), a relationship that was maintained throughout all age groups (<18, 18 to 39, and ≥40 years). Older patients (≥40 years of age) with remote episodes of syncope (>5 years before initial evaluation) did not show an increased risk of sudden death (adjusted hazard ratio 0.38, 95% confidence interval 0.05 to 2.74). Conclusions— In the present large cohort of patients with hypertrophic cardiomyopathy, unexplained syncope was a risk factor for sudden death. Patients with syncopal events that occurred in close temporal proximity to the initial evaluation showed a substantially higher risk of sudden death than patients without syncope. Older patients with remote syncopal events did not show an increased risk.
Heart | 2007
Carla Lofiego; Elena Biagini; Ferdinando Pasquale; Marinella Ferlito; Guido Rocchi; Enrica Perugini; Letizia Bacchi-Reggiani; Giuseppe Boriani; Ornella Leone; Kadir Caliskan; F J ten Cate; Fernando M. Picchio; Angelo Branzi; Claudio Rapezzi
Objectives: To investigate diagnostic routes, echocardiographic substrates, outcomes and prognostic factors in patients with isolated ventricular non-compaction (IVNC) identified by echocardiographic laboratories with referral from specialists and primary care physicians. Patients and design: Since 1991, all patients with suspected IVNC were flagged and followed up on dedicated databases. Patients were divided into symptom-based and non-symptom-based diagnostic subgroups. Results: 65 eligible patients were followed up for 6–193 months (mean 46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%) LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was characterised by younger age, lower prevalence of ECG abnormalities, better systolic function and lower left atrial size, whereas the extent of non-compaction was not different. No major cardiovascular events occurred in the non-symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients experienced cardiovascular death or heart transplantation (p = 0.01, Kaplan–Meier analysis). Independent predictors of cardiovascular death or heart transplantation were New York Heart Association class III–IV, sustained ventricular arrhythmias and left atrial size. Conclusions: IVNC is associated with a broad spectrum of clinical and pathophysiological findings, and the overall natural history and prognosis may be better than previously thought. Adult patients with incidental or familial discovery of IVNC have an encouraging outlook, whereas those who have symptoms of heart failure, a history of sustained ventricular tachycardia or an enlarged left atrium have an unstable course and more severe prognosis.
Nature Reviews Cardiology | 2010
Claudio Rapezzi; Candida Cristina Quarta; Letizia Riva; Simone Longhi; Ilaria Gallelli; Massimiliano Lorenzini; Paolo Ciliberti; Elena Biagini; Fabrizio Salvi; Angelo Branzi
A nonhereditary form of systemic amyloidosis associated with wild-type transthyretin causes heart involvement predominantly in elderly men (systemic senile amyloidosis, or SSA). However, hereditary transthyretin-related amyloidosis (ATTR) is the most frequent form of familial systemic amyloidosis, a group of severe diseases with variable neurological and organ involvement. ATTR remains a challenging and widely underdiagnosed condition, owing to its extreme phenotypic variability: the clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to a strictly cardiac presentation. Such heterogeneity principally results from differential effects of the various reported transthyretin mutations, the geographic region the patient is from and, in the case of the most common mutation, Val30Met, whether or not large foci of cases occur (endemic versus nonendemic aggregation). Genetic or environmental factors (such as age, sex, and amyloid fibril composition) also contribute to the heterogeneity of ATTR, albeit to a lesser extent. The existence of exclusively or predominantly cardiac phenotypes should lead clinicians to consider the possibility of ATTR in all patients who present with an unexplained increase in left ventricular wall thickness at echocardiography. Assessment of such patients should include an active search for possible red flags that can point to the correct final diagnosis.
Coronary Artery Disease | 2006
Olaf Schouten; Leslee J. Shaw; Eric Boersma; Jeroen J. Bax; Miklos D. Kertai; Harm H.H. Feringa; Elena Biagini; Niels F.M. Kok; Hero van Urk; Abdou Elhendy; Don Poldermans
ObjectivePerioperative &bgr;-blocker therapy has been proposed to improve outcome. Most of the trials conducted, however, lacked statistical power to evaluate the incidence of hard cardiac events and the relationship to the type of surgery. Therefore, we conducted a meta-analysis of all randomized controlled trials in which &bgr;-blocker therapy was evaluated. MethodsAn electronic search of published reports on Medline was undertaken to identify studies published between January 1980 and November 2004 in English language journals. All studies reported on at least one of three endpoints: perioperative myocardial ischemia, perioperative nonfatal myocardial infarction, and cardiac mortality. Type of surgery, defined as low, intermediate, and high risk according to the American College of Cardiology/American Heart Association guidelines, was noted. ResultsIn total, 15 studies were identified, which enrolled 1077 patient. No significant differences were observed in baseline clinical characteristics between patients randomized to &bgr;-blocker therapy and control/placebo. Beta-blocker therapy was associated with a 65% reduction in perioperative myocardial ischemia (11.0% vs. 25.6%; odds ratio 0.35, 95% confidence interval 0.23–0.54; P<0.001). Furthermore, a 56% reduction in myocardial infarction (0.5% vs. 3.9%, odds ratio 0.44, 95% confidence interval 0.20–0.97; P=0.04) and a 67% reduction (1.1% vs. 6.1%, odds ratio 0.33, 95% confidence interval 0.17–0.67; P=0.002) in the composite endpoint of cardiac death and nonfatal myocardial infarction were observed. No statistical evidence was observed for heterogeneity in the treatment effect in subgroups according to type of surgery (P for heterogeneity 0.2). ConclusionThis meta-analysis shows that &bgr;-blocker use in noncardiac surgical procedures is associated with a significant reduction of perioperative cardiac adverse events.
Heart | 2006
Vittoria Rizzello; Don Poldermans; Arend F.L. Schinkel; Elena Biagini; Eric Boersma; Abdou Elhendy; Fabiola B. Sozzi; Alexander P.W.M. Maat; Filippo Crea; Jos R.T.C. Roelandt; Jeroen J. Bax
Objective: To evaluate the relative merits of viability and ischaemia for prognosis after revascularisation. Methods: Low–high dose dobutamine stress echocardiography (DSE) was performed before revascularisation in 128 consecutive patients with ischaemic cardiomyopathy (mean (SD) left ventricular ejection fraction (LVEF) 31 (8)%). Viability (defined as contractile reserve (CR)) and ischaemia were assessed during low and high dose dobutamine infusion, respectively. Cardiac death was evaluated during a five year follow up. Clinical, angiographic, and echocardiographic data were analysed to identify predictors of events. Results: Univariable predictors of cardiac death were the presence of multivessel disease (hazard ratio (HR) 0.21, p < 0.001), baseline LVEF (HR 0.90, p < 0.0001), wall motion score index (WMSI) at rest (HR 4.02, p = 0.0006), low dose DSE (HR 7.01, p < 0.0001), peak dose DSE (HR 4.62, p < 0.0001), the extent of scar (HR 1.39, p < 0.0001), and the presence of CR in ⩾ 25% of dysfunctional segments (HR 0.34, p = 0.02). The best multivariable model to predict cardiac death included the presence of multivessel disease, WMSI at low dose DSE, and the presence of CR in ⩾ 25% of the severely dysfunctional segments (HR 9.62, p < 0.0001). Inclusion of ischaemia in the model did not provide additional predictive value. Conclusion: The findings of the present study illustrate that in patients with ischaemic cardiomyopathy, the extent of viability (CR) is a strong predictor of long term prognosis after revascularisation. Ischaemia did not add significantly in predicting outcome.
Circulation | 2005
Christopher Lee; Folkert J. ten Cate; Marcel L. Geleijnse; Marcel Kofflard; Chiara Pedone; Lex A. van Herwerden; Elena Biagini; Wim B. Vletter; Patrick W. Serruys
Background—The purpose of this study was to compare percutaneous transluminal septal myocardial ablation (PTSMA) and septal myectomy combined with mitral leaflet extension (MLE) in symptomatic hypertrophic obstructive cardiomyopathy patients with an enlarged anterior mitral valve leaflet (AMVL). Both PTSMA and myectomy reduce septal thickness and left ventricular outflow tract (LVOT) gradient; however, an uncorrected enlarged AMVL may predispose to residual systolic anterior motion (SAM) after successful standard myectomy or PTSMA. Myectomy with MLE previously demonstrated superior hemodynamic results compared with standard myectomy, but its value relative to PTSMA is unknown. Methods and Results—Twenty-nine patients (aged 44±12 years) underwent myectomy with MLE, and 43 patients (aged 52±17 years) underwent PTSMA. Mitral leaflet area was similar in both groups (16.7±3.4 versus 15.9±2.7 cm2, respectively). After PTSMA, 2 patients died, 4 needed a reintervention, and 4 required a permanent pacemaker for complete heart block. After surgery, only 1 patient needed a reintervention. At 1-year follow-up, LVOT gradients did not differ between surgical and PTSMA patients (17±14 versus 23±19 mm Hg, respectively). Preinterventional mitral regurgitation grade was more severe in the surgical group, but with myectomy combined with MLE, the residual grade was similar to that of PTSMA. Mean SAM grade decreased significantly more after surgery (from 2.9±0.3 to 0.5±0.7 mm Hg versus from 2.8±0.5 to 1.3±0.9 mm Hg, P<0.05). Conclusions—PTSMA in these selected patients with hypertrophic obstructive cardiomyopathy had more periprocedural complications and resulted in more reinterventions. Hemodynamic results (SAM grade and reduction in mitral regurgitation) were better in surgical patients.
Circulation | 2004
Vittoria Rizzello; Don Poldermans; Eric Boersma; Elena Biagini; Arend F.L. Schinkel; Boudewijn J. Krenning; Abdou Elhendy; Eleni C. Vourvouri; Fabiola B. Sozzi; Alexander P.W.M. Maat; Filippo Crea; Jos R.T.C. Roelandt; Jeroen J. Bax
Background—In patients with ischemic cardiomyopathy, left ventricular (LV) remodeling is an important prognostic indicator. The precise relation between viable myocardium, revascularization, and ongoing or reversed remodeling is unknown and was evaluated in the present study. Methods and Results—A total of 100 patients with ischemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability and LV geometry (volumes and shape). At a mean of 10.2 months and 4.5 years after revascularization, resting echocardiography was repeated to evaluate LV remodeling. Long-term follow-up (mean 5±2 years) data were obtained. According to dobutamine stress echocardiography, 44 patients (44%) were defined as viable (≥4 viable segments) and 56 as nonviable. After revascularization, 40 patients (43%) had ongoing LV remodeling and 53 (57%) did not (in 7 patients who died early after revascularization, postoperative echocardiographic evaluation was not available). On multivariable analysis, the number of viable segments was the only predictor of ongoing LV remodeling (OR 0.60, 95% CI 0.48 to 0.75; P<0.0001). The likelihood of LV remodeling decreased as the number of viable segments increased. During the follow-up, reverse remodeling was present in viable patients, whereas in nonviable patients, LV volumes significantly increased, which indicates ongoing LV remodeling. At follow-up, viable patients also showed a persistent improvement of heart failure symptoms and fewer cardiac events than nonviable patients (P<0.05). Conclusions—In patients with ischemic cardiomyopathy, a substantial amount of viable myocardium prevents ongoing LV remodeling after revascularization and is associated with persistent improvement of symptoms and better outcome.
American Journal of Cardiology | 2008
Elena Biagini; Paolo Spirito; Ornella Leone; Fernando M. Picchio; Fabio Coccolo; Luca Ragni; Carla Lofiego; Francesco Grigioni; Luciano Potena; Guido Rocchi; Letizia Bacchi-Reggiani; Giuseppe Boriani; Daniela Prandstraller; Eloisa Arbustini; Angelo Branzi; Claudio Rapezzi
Heart transplantation (HT) is the sole therapeutic option for selected patients with hypertrophic cardiomyopathy (HC) and refractory heart failure. However, the results of HT have not been systematically investigated in HC. We assessed the pathophysiologic profile of HT candidates and the outcome after transplantation in 307 patients with HC consecutively evaluated at our tertiary referral center from 1987 to 2005; follow-up was 9.9+8.2 years. Outcome of recipients with HC was compared with that of 141 patients who underwent transplantation for idiopathic dilated cardiomyopathy at our center over the same period. Of 21 patients with HC who entered the transplantation list, 20 had end-stage evolution with systolic dysfunction and 1 had an extremely small left ventricular cavity with impaired filling and recurrent cardiogenic shock during paroxysmal atrial fibrillation. Of 33 study patients with HC who showed end-stage evolution during follow-up, the 23 who were included on the waiting list or died from refractory heart failure (2 patients) were significantly younger than the 10 patients who remained clinically stable (37+/-14 vs 57+/-17 years, p=0.004). Of the 21 HT candidates, 18 underwent transplantation during follow-up. In heart transplant recipients, 7-year survival rate was 94% and not different from that of the 141 patients who received transplants for idiopathic dilated cardiomyopathy (p=0.66). In conclusion, long-term outcome after HT in patients with HC is favorable and similar to that of patients with idiopathic dilated cardiomyopathy. In patients with end-stage HC, young age is associated with more rapid progression to refractory heart failure.