Maria Rosa Conte

Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy

OBJECTIVES We sought to assess the occurrence and clinical significance of stroke and peripheral arterial embolizations at non-central nervous system sites in a large, community-based cohort with hypertrophic cardiomyopathy (HCM). BACKGROUND Such vascular events are insufficiently appreciated complications of HCM for which there is limited information on occurrence, clinical profile and determinants. METHODS We assessed the clinical features of patients with stroke and other peripheral vascular events in a consecutive group of patients with HCM from four regional cohorts not subject to significant tertiary referral bias. RESULTS Of the 900 patients, 51 (6%) patients experienced stroke or other vascular events over 7 +/- 7 years, including 44 patients with stroke; 21 (41%) of these 51 patients died or were permanently disabled. The overall incidence was 0.8%/year and 1.9% for patients >60 years old. Age at first event ranged from 29 to 86 years (mean 61 +/- 14 years). Most (n = 37; 72%) events occurred in those >50 years, although 14 (28%) younger patients (< or = 50 years) also had events. Multivariate analysis showed stroke and other peripheral vascular events to be independently associated with congestive symptoms and advanced age, as well as with atrial fibrillation (in 45 [88%] of 51 patients), at the initial evaluation. The cumulative incidence of these events among patients with atrial fibrillation was significantly higher in non-anticoagulated patients as compared with patients receiving warfarin (31% vs. 18%; p < 0.05). CONCLUSIONS Stroke and peripheral embolizations showed a 6% prevalence rate and an incidence of 0.8%/year in a large, unselected HCM group. These profound complications of HCM, which may lead to disability and death, were substantially more common in the elderly, occurred almost exclusively in patients with paroxysmal or chronic atrial fibrillation and appeared to be reduced in frequency by anticoagulation.

Syncope and risk of sudden death in hypertrophic cardiomyopathy

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.

Risk associated with pregnancy in hypertrophic cardiomyopathy

OBJECTIVES We sought to assess mortality and morbidity in pregnant women with hypertrophic cardiomyopathy (HCM). BACKGROUND The risk associated with pregnancy in women with HCM is an important and increasingly frequent clinical issue for which systematic data are not available and a large measure of uncertainty persists. METHODS Maternal mortality in 91 consecutively evaluated families with HCM was compared with that reported in the general population. The study cohort included 100 women with HCM with one or more live births, for a total of 199 live births. Morbidity related to HCM during pregnancy was investigated in 40 women evaluated within five years of their pregnancy. RESULTS Two pregnancy-related deaths occurred, both in patients at a particularly high risk. The maternal mortality rate was 10 per 1,000 live births (95% confidence interval [CI] 1.1 to 36.2/1,000) and was in excess of the expected mortality in the general Italian population (relative risk 17.1, 95% CI 2.0 to 61.8). In the 40 patients evaluated within close proximity of their pregnancy, 1 (4%) of the 28 who were previously asymptomatic and 5 (42%) of the 12 with symptoms progressed to functional class III or IV during pregnancy (p < 0.01). One patient had atrial fibrillation and one had syncope, both of whom had already experienced similar and recurrent events before their pregnancy. CONCLUSIONS Maternal mortality is increased in patients with HCM compared with the general population. However, absolute maternal mortality is low and appears to be principally confined to women at a particularly high risk. In the presence of a favorable clinical profile, the progression of symptoms, atrial fibrillation, and syncope are also uncommon during pregnancy.

Infective Endocarditis in Hypertrophic Cardiomyopathy Prevalence, Incidence, and Indications for Antibiotic Prophylaxis

BACKGROUND The literature on infective endocarditis in hypertrophic cardiomyopathy (HCM) is virtually confined to case reports. Consequently, the risk of endocarditis in HCM remains undefined. METHODS AND RESULTS We assessed the occurrence of endocarditis in 810 HCM patients evaluated between 1970 and 1997. Endocarditis was diagnosed in 10 patients, 2 of whom were excluded from analysis of prevalence and incidence because they were referred for acute endocarditis. At first evaluation, echocardiographic features consistent with prior endocarditis were identified in 3 of 808 patients, a prevalence of 3.7 per 1000 patients (95% CI, 0.8 to 11). Of 681 patients who were followed, 5 developed endocarditis, an incidence of 1.4 per 1000 person-years (95% CI, 0.5 to 3.2); outflow obstruction was present in each of these 5 patients and was associated with the risk of endocarditis (P=0.006). In the 224 obstructive patients, incidence of endocarditis was 3.8 per 1000 person-years (95% CI, 1.6 to 8.9) and probability of endocarditis 4. 3% at 10 years. Left atrial size was also associated with the risk of endocarditis (P=0.007). In patients with both obstruction and atrial dilatation (>/=50 mm), incidence of endocarditis increased to 9.2 per 1000 person-years (95% CI, 2.5 to 23.5). Analysis of all 10 patients with endocarditis identified outflow obstruction in each and atrial dilatation in 7. CONCLUSIONS Endocarditis in HCM is virtually confined to patients with outflow obstruction and is more common in those with both obstruction and atrial dilatation. These results indicate that antibiotic prophylaxis is required only in patients with obstructive HCM.

Epidemiology and patterns of care of patients admitted to Italian Intensive Cardiac Care units: the BLITZ-3 registry.

Background Intensive cardiac care units (ICCUs) have shifted from the observation of patients with myocardial infarction to the care of different acute cardiac diseases. However, few data on such an evolution are available. Methods and results From 7 to 20 April 2008, 6986 consecutive patients admitted to 81% of Italian ICCUs were prospectively enrolled. Patients observed were mainly elderly men (median age 72 years) with several co-morbidities. Most of them were triaged to ICCU from the emergency room, but 15% of admissions were transfer-in from other hospitals. Several diagnostic and therapeutic procedures were applied (78% had echocardiography and 35% coronary angiography) during the ICCU stay [median length 4 days, interquartile range (IQR) 2–5]. The discharge diagnosis was ST-elevation acute coronary syndrome (ACS) in 21%, non-ST-elevation ACS in 31%, acute heart failure (AHF) in 14% and other acute non-ACS, non-AHF cardiac diseases in 34%. Of those with ST-elevation ACS, 60% received reperfusion (15% fibrinolysis and 45% primary percutaneous coronary intervention). The overall in-ICCU crude mortality was 3.3%. Conclusion The BLITZ-3 survey provides a unique snapshot of current epidemiology and patterns of care of patients admitted to ICCUs. Although ACS still remains the most frequent admission diagnosis, the number of non-ACS patients is substantial. However, the correct standard of care for these non-ACS patients has to be defined.

Relationship of ECG findings to phenotypic expression in patients with hypertrophic cardiomyopathy: A cardiac magnetic resonance study ☆

BACKGROUND The 12-lead electrocardiogram (ECG) is considered an essential screening tool for hypertrophic cardiomyopathy (HCM). A vast array of ECG abnormalities has been described in HCM, although their relationship to left ventricle (LV) morphology and degree of hypertrophy appears elusive. Aim of this study was to assess the relationship of ECG patterns with the HCM phenotype assessed according to the novel opportunities offered by cardiac magnetic imaging (CMR). METHODS CMR and 12-lead ECG were performed in 257 HCM patients. Severity of ECG abnormalities was defined by the sum of 9 criteria: abnormal cardiac rhythm, QRS duration ≥ 100 ms, Romhilt-Estes score ≥ 5, fascicular block (LAHB) and/or bundle-branch block (LBBB or RBBB), ST-T abnormalities, ST-T segment elevation ≥ 0.2 mV, prolonged QTc interval, pathological Q waves, absence of normal Q wave. Four ECG groups were identified: normal (0 criteria); mildly abnormal (1-3 criteria); moderately abnormal (4-6 criteria); markedly abnormal (7-9 criteria). RESULTS There was a direct relationship between severity of ECG abnormalities and HCM phenotype. LV mass index was normal in most patients with normal ECG and progressively increased with each class of ECG score, from 70.9 ± 18.6g/m(2) in patients with normal ECG to 107.1 ± 55.1g/m(2) among those with markedly abnormal ECG (p=<0.0001). Likewise, the prevalence and extent of late gadolinium enhancement (LGE) increased significantly with the ECG score, from 37% in patients with normal ECG to 93% in patients with markedly abnormal ECG (overall p=0.0012). A normal ECG had a negative predictive accuracy of 96% for markedly increased LV mass (>91 g/m(2) for men and >69 g/m(2) for women), and of 100% for maximum LV thickness ≥ 30 mm. CONCLUSIONS In a large HCM cohort, the number and severity of ECG abnormalities were directly related to phenotypic expression as revealed by CMR. Although false negative ECG findings remain a challenge in population screenings for HCM, a normal ECG proved effective in ruling out severe LV hypertrophy, suggesting potential implications for long-term follow-up of HCM patients and family members. A simple score for quantification of ECG abnormalities in HCM patients is proposed.

Cardiogenic shock complicating acute myocardial infarction in the elderly: predictors of long-term survival.

Background: Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI), associated with a high mortality. A significant improvement in survival has been reported with immediate coronary revascularization. However, there is no clear evidence of such an improvement amongst older patients. The aim of our work was to evaluate in‐hospital and long‐term outcomes in the group of elderly AMI patients with CS (≥75 years old). Methods: We collected data of 157 consecutive AMI patients with CS who underwent percutaneous coronary intervention (PCI) and compared clinical and procedural characteristics and in‐hospital and long‐term outcomes between patients <75 years and patients ≥75 years old. Results: There were 58 patients (36.9%) with age ≥75 years and 99 patients (63.1%) with age <75 years. Patients were followed up for an average period of 34 months (range 5–69). In‐hospital and long‐term mortality was significantly higher in the older group (55 vs. 25%, P < 0.0001; and 62.1 vs. 37.3%, P = 0.005, respectively). Multivariate predictors of in‐hospital mortality were age ≥75 years (hazard ratio 1.81, 95% CI 1.006–3.27, P = 0.04) and PCI failure (hazard ratio 2.67, 95% CI 1.34–5.307, P = 0.005), whereas, the only multivariate predictor of long‐term mortality was PCI failure (hazard ratio 2.88, 95% CI 1.52–5.46, P = 0.001). Age ≥75 years showed only a trend toward statistical significance (hazard ratio 1.62, 95% CI 0.96–2.76, P = 0.07). Conclusions: In elderly AMI patients with CS, PCI can be performed with an acceptable risk that seems lower than that reported in most previous studies.

Primary angioplasty and routine utilization of thrombus aspiration devices: feasibility and results in a consecutive series of 486 patients.

Background Primary percutaneous transluminal coronary angioplasty (PTCA) is the treatment of choice for acute ST-segment elevation myocardial infarction (STEMI) in high-volume centres with experienced operators, but is often limited by a suboptimal microvascular perfusion due to distal embolization and impaired myocardial perfusion. The present study investigates whether routine use of thrombus aspiration (TA) devices is feasible in daily practice, along with its safety and effectiveness. Methods This study is based on a series of 486 consecutive STEMI patients treated at our single institution by the same three operators (from 2001 to 2005). They underwent primary PTCA with or without TA according to these angiographic features: infarct related artery (IRA) diameter ≥ 3 mm; thrombotic occlusion or angiographic evidence of thrombus; absence of severe proximal tortuosity or calcification. We evaluate the efficacy of TA in terms of procedural success, coronary thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), resolution ≥ 50% of ST segment elevation, and clinical events during hospital stay and at 6-month follow-up. Results A total of 486 primary PTCAs were performed, 217 (44.6%) with TA as a first device using RESCUE (n = 65), EXPORT (n = 140) and DIVER-CE (n = 12) catheters. In 141 (65%) cases, macroscopic material was aspirated. The patients submitted to TA were more often males (84.7% versus 71.7%, P < 0.05) and younger (age: 61.02 ± 11.91 versus 64.47 ± 10.59 years, P < 0.01) than patients treated with traditional PTCA and the IRA was more frequently occluded at angiography (basal TIMI 0: 70.5% versus 47.9%). Application of the TA did not increase the complexity of the procedure (door-to-balloon times, minutes of fluoroscopy and amount of dye). TA alone was effective to restore TIMI 3 flow in 187 cases (86.2%) as a first device and in three other cases (1.4%) after predilatation with balloon. Direct stenting without predilatation was possible in 144 cases (66.4%) after TA. TA was not effective in 27 cases (12.4%) and this subgroup had both angiographic and clinical unfavourable results in comparison with the effective TA group (final TIMI 1 in 11.1% versus 0.5%, P < 0.015; final MBG 1 in 55.5% versus 9.5%, P < 0.001; lack of ST segment resolution ≥ 50% in 44.4% versus 7.9%, P < 0.001; in-hospital mortality 14.8% versus 2.6%, P < 0.05 and mortality at 6 months 18.5% versus 3.1%, P < 0.05). In the whole TA population, final TIMI 3 flow was achieved in 203 cases (93.5%), final MBG 3 in 145 cases (66.8%) and ST segment resolution ≥ 50% in 185 cases (85.2%), in-hospital mortality was 4.1% and cumulative mortality at 6-month follow-up was 5.5%. Conclusions In our case series, 486 consecutive unselected patients with STEMI were treated in a primary PTCA high-volume centre using TA devices. Our study demonstrates that, in STEMI patients treated with primary PTCA, a routine strategy with TA before angioplasty guided by angiographic selection criteria is feasible in almost 50% of cases, is safe and effective, does not increase procedural time and offers good results in terms of tissue perfusion, both epicardial (TIMI flow) and myocardial (MBG, ST regression). When successfully performed, TA identifies a population with favourable in-hospital and 6-month outcome.

Rest perfusion abnormalities in hypertrophic cardiomyopathy: correlation with myocardial fibrosis and risk factors for sudden cardiac death

Aim To measure the prevalence of abnormal rest perfusion in a population of consecutive patients with known hypertrophic cardiomyopathy (HCM) referred for cardiovascular MRI (CMR), and to assess any associations between abnormal rest perfusion and the presence, pattern, and severity of myocardial scar and the presence of risk factors for sudden death. Materials and methods Eighty consecutive patients with known HCM referred for CMR underwent functional imaging, rest first-pass perfusion, and late gadolinium enhancement (LGE). Results Thirty percent of the patients had abnormal rest perfusion, all of them corresponding to areas of mid-myocardial LGE and to a higher degree of segmental hypertrophy. Rest perfusion abnormalities correlated with more extensive and confluent LGE. The subgroup of patients with myocardial fibrosis and rest perfusion abnormalities (fibrosis+/perfusion+) had more than twice the incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring in comparison to patients with myocardial fibrosis and normal rest perfusion (fibrosis+/perfusion–) and patients with no fibrosis and normal rest perfusion (fibrosis–/perfusion–). Conclusions First-pass perfusion CMR identifies abnormal rest perfusion in a significant proportion of patients with HCM. These abnormalities are associated with the presence and distribution of myocardial scar and the degree of hypertrophy. Rest perfusion abnormalities identify patients with increased incidence of episodes of non-sustained ventricular tachycardia on Holter monitoring, independently from the presence of myocardial fibrosis.

Long-Term Outcomes of Percutaneous Coronary Interventions With Stent Implantation in Patients ≤40 Years Old

Data on the long-term prognosis of percutaneous coronary intervention (PCI) in young patients are limited. The aim of the present study was to report the immediate and long-term clinical outcomes in a consecutive series of young patients with premature coronary artery disease who underwent PCI with stent implantation. During the study period (2005 to 2010), 214 consecutive patients aged ≤40 years who had undergone PCI with a bare metal stent or drug-eluting stent implantation were retrospectively selected and analyzed. Primary end point of this study was the incidence of major adverse cardiac and cerebrovascular events at short- and long-term follow-up. Mean age was 36.3 ± 3.5 years and 88.3% of patients were men. Three-quarters were active smokers and all patients had ≥1 conventional cardiovascular risk factor. The total number of implanted stents was 272 (154 bare metal stent and 118 drug-eluting stent). During the hospital stay, no patient died, and the incidence of major adverse cardiac and cerebrovascular events was 2.3%. No additional events had occurred at 30 days of follow-up. At a median follow-up of 757 days (interquartile range 365 to 1,818), the overall death rate was 0.9%, and a new revascularization procedure was needed in 12.6% of patients. The major adverse cardiac and cerebrovascular event-free survival rate at the median follow-up point and 1,818 days was 89.6% and 84.2%, respectively. Active smoking and left ventricular ejection fraction <50% were independent predictors of major adverse cardiac and cerebrovascular events. In conclusion, PCI in young patients lead to excellent results in short- and long-term follow-up and should be considered as the treatment of choice. Traditional risk factors are important prognostic determinants of adverse events and might help identify higher risk patients within this cohort.