End-stage hypertrophic cardiomyopathy (ES-HC) has an ominous prognosis. Whether genotype can influence ES-HC occurrence is unresolved. We assessed the spectrum and clinical correlates of ...HC-associated mutations in a large multicenter cohort with end-stage ES-HC. Sequencing analysis of 8 sarcomere genes (MYH7, MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1) and 2 metabolic genes (PRKAG2 and LAMP2) was performed in 156 ES-HC patients with left ventricular (LV) ejection fraction (EF) <50%. A comparison among mutated and negative ES-HC patients and a reference cohort of 181 HC patients with preserved LVEF was performed. Overall, 131 mutations (36 novel) were identified in 104 ES-HC patients (67%) predominantly affecting MYH7 and MYBPC3 (80%). Complex genotypes with double or triple mutations were present in 13% compared with 5% of the reference cohort (p = 0.013). The distribution of mutations was otherwise indistinguishable in the 2 groups. Among ES-HC patients, those presenting at first evaluation before the age of 20 had a 30% prevalence of complex genotypes compared with 19% and 21% in the subgroups aged 20 to 59 and ≥60 years (p = 0.003). MYBPC3 mutation carriers with ES-HC were older than patients with MYH7, other single mutations, or multiple mutations (median 41 vs 16, 26, and 28 years, p ≤0.001). Outcome of ES-HC patients was severe irrespective of genotype. In conclusion, the ES phase of HC is associated with a variable genetic substrate, not distinguishable from that of patients with HC and preserved EF, except for a higher frequency of complex genotypes with double or triple mutations of sarcomere genes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract The Objective of this study is to investigate the prognostic significance of 12-lead electrocardiogram (ECG) patterns in a large multicenter cohort of patients with hypertrophic ...cardiomyopathy (HC). 1004 consecutive patients with HC and a recorded standard ECG (64% men, mean age 50±16 years) were evaluated at 4 Italian centres. The study end-points were sudden cardiac death (SCD) or surrogates, including appropriate implanted cardiac defibrillator discharge and resuscitated cardiac arrest) and major cardiovascular events (including SCD or surrogates and death due to heart failure, cardioembolic stroke or heart transplantation). Prevalence of baseline ECG characteristics was: normal ECG 4%, ST-segment depression 56%, pseudo-necrosis waves 33%, “pseudo-STEMI” pattern 17%, QRS duration ≥120msec 17%, giant inverted T waves 6%, low QRS voltages 3%. During a mean follow-up of 7.4±6.8 years 77 patients experienced SCD or surrogates and 154 patients experienced major cardiovascular events. Independent predictors of SCD or surrogates were unexplained syncope (H.R. 2.5, 95%CI 1.4-4.5, p=0.003), left ventricular ejection fraction <50% (H.R. 3.5, 95%CI 1.9-6.7, p=0.0001), non-sustained ventricular tachycardia (H.R. 1.7, 95%CI 1.1-2.6, p 0.027), “pseudo-STEMI” pattern (H.R. 2.3, 95%CI 1.4-3.8, p 0.001), QRS duration ≥120 msec (H.R. 1.8, 95%CI 1.1-3.0, p 0.033) and low QRS voltages (H.R. 2.3, 95%CI 1.01-5.1, p 0.048). Independent predictors of major cardiovascular events death were age (HR 1.02, 95%CI 1.01-1.03, p=0.0001), LV ejection fraction <50% (HR 3.73, 95%CI 2.39-5.83, p=0.0001), “pseudo-STEMI” pattern (HR 1.66, 95%CI 1.13-2.45, p=0.010), QRS duration ≥120 msec (HR 1.69, 95%CI 1.16-2.47, p=0.007) and prolonged QTc interval (HR 1.68, 95%CI 1.21-2.34, p=0.002). In conclusion a detailed qualitative and quantitative ECG analysis provides independent predictors of prognosis that could be integrated with the available score systems to improve the power of the current model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The clinical utility of stress testing in patients without angina pectoris after revascularization has been questioned. Dobutamine stress echocardiography (DSE) is an established technique for ...detection of myocardial ischemia and cardiac risk stratification. We studied the prognostic value of DSE in 393 patients without typical angina pectoris after coronary revascularization. Ischemia was incremental to clinical data in predicting all-cause death (hazard ratio 3.5, 95% confidence interval 1.8 to 6.7) and cardiac death (hazard ratio 4.2, 95% confidence interval 1.8 to 9.8). In conclusion, myocardial ischemia during DSE is independently associated with an increased risk of all-cause mortality and cardiac death in these patients after adjustment for clinical data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). ...Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Doppler echocardiographic pattern of restrictive left ventricular (LV) filling has proved to be an important predictor of clinical course and prognosis in dilated cardiomyopathy. However, the ...relation between restrictive filling pattern and clinical course has not been systematically investigated in hypertrophic cardiomyopathy (HC). We assessed the prognostic implications of the Doppler restrictive filling pattern in 239 consecutive patients with HC in whom Doppler measurements of LV filling had been systematically recorded at initial evaluation and during follow-up. Restrictive LV filling was identified in 14 patients (5.9%) at initial evaluation and developed in 22 (9.2%) during follow-up. A close relation was identified between restrictive filling pattern and end-stage HC, with patients with restrictive filling showing a sixfold increase in risk of developing end-stage HC (hazard ratio 6.25, 95% confidence interval 1.90 to 20.57, p = 0.003). Over a median follow-up of 9.7 years, 22 patients (9.2%) died suddenly or received appropriate cardioverter–defibrillator interventions, and 54 (22.6%) had HC-related death or underwent heart transplantation. In a set of univariate and multivariate analyses including each of the generally accepted risk factors for cardiac death in HC, the restrictive filling pattern was a strong and independent marker of increased risk (hazard ratio for sudden cardiac events 3.51, 95% confidence interval 1.37 to 8.95, p = 0.009; hazard ratio for HC-related death or heart transplantation 3.54, 95% confidence interval 1.91 to 6.57, p <0.001) compared to patients without restrictive filling. In conclusion, in our study cohort, the Doppler pattern of restrictive LV filling proved to be a strong predictor of sudden death and HC-related death, independently of other markers for unfavorable prognosis in this disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of nonobstructive HC with peculiar characteristics. The investigators report a series of 13 consecutive Caucasian patients with a ...suspicion or diagnosis of apical HC on the basis of electrocardiographic and/or echocardiographic findings who prospectively underwent magnetic resonance imaging with late gadolinium enhancement (LGE) evaluation. All but 1 patient presented T-wave inversion in the anterolateral leads on electrocardiogram, with a mean maximum negative T wave of 7.0 ± 3.9 mm. Echocardiography provided correct diagnoses in 9/13 patients (69%), while in 4 patients echocardiographic results were normal or inconclusive. Magnetic resonance imaging showed a spadelike morphology of the left ventricle in 6 patients and identified an apical aneurysm in 4. Eleven patients (85%) presented LGE with a mean percentage of 2.3 ± 2.6% of total left ventricular mass. In 9 (69%) patients LGE was limited to the hypertrophic segments while in 6 (46%) patients it was also present in nonhypertrophic segments. In conclusion, magnetic resonance imaging in patients with apical HC showed a high incidence of apical aneurysms and a peculiar distribution of LGE, that was not limited to hypertrophic segments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In acute aortic dissection (AAD), timely diagnosis is challenging. However, dedicated studies of the entity and determinants of delay are currently lacking. We surveyed pre-/in-hospital time to ...diagnosis and explored risk factors for diagnostic delay. We analyzed the dedicated database of a metropolitan AAD network (161 patients diagnosed since 1996; 115 Stanford type A) in terms of hospital arrival times (from pain to presentation at any hospital) and in-hospital diagnostic times (presentation to final diagnosis). Median (interquartile range) in-hospital diagnostic times were approximately twofold greater than hospital arrival times (177 minutes, 644, vs 75 minutes, 124, p = 0.0001, Wilcoxon test). Median annual in-hospital diagnostic times were most often ∼3 hours (spread was wide, but decreased after 2001; ρ = −0.94, p = 0.005). Risk factors (univariate analysis) for in-hospital diagnostic time >75th percentile (12 hours) included pleural effusion (odds ratio 3.96, 95% confidence interval 1.80 to 8.69), dyspneic presentation (odds ratio 3.33, 95% confidence interval 1.93 to 8.59), and age <70 years (odds ratio 2.34, 95% confidence interval 1.03 to 5.36). Systolic arterial pressure ≤105 mm Hg decreased the likelihood of lengthy diagnosis (odds ratio 0.08, 95% confidence interval 0.01 to 0.59). In patients (n = 82) with routine values (since 2000), troponin positivity (odds ratio 3.63, 95% confidence interval 1.12 to 11.84) and an acute coronary syndrome–like electrocardiogram (odds ratio 2.88, 95% confidence interval 1.01 to 8.17) were also risk factors. In conclusion, in a metropolitan setting, most of the diagnostic delay may occur in hospital. At presentation, pleural effusion, troponin positivity, acute coronary syndrome–like electrocardiogram, and dyspnea are possible “clinical confounders” associated with particularly long in-hospital diagnostic times.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abciximab therapy during primary percutaneous coronary intervention (PCI) has shown to ameliorate left ventricular (LV) function recovery in patients with ST elevated myocardial infarction. High-dose ...bolus tirofiban has similar effect on platelet inhibition. Whether this is associated with comparable efficacy on LV function recovery remains unclear. We sought to evaluate the impact on LV function of high-dose bolus tirofiban or abciximab in patients undergoing primary PCI with the predictors of favorable (≥50%) LV ejection fraction (EF) and LV function recovery at 30 days. We studied 314 patients (abciximab n = 154; tirofiban n = 160) undergoing primary PCI in the randomized Facilitated Angioplasty with Tirofiban or Abciximab (FATA) trial. LVEF was assessed within 48 hours and at 30 days after primary PCI. In patients with systolic dysfunction at baseline, LV function recovery was defined by either increase of LVEF ≥10% compared with baseline or LVEF ≥50%. Similar LVEF was observed in the 2 groups postprocedure (abciximab 49.7 ± 10.1% vs tirofiban 49.3 ± 10.1%, p = 0.9) and at 30 days (abciximab 53.1 ± 9.8% vs tirofiban 52.5 ± 10.2%, p = 0.6). Independent predictors of 30-day LVEF ≥50% were preprocedure Thrombolysis In Myocardial Infarction flow class >0 (odds ratio = 2.4, 95% confidence interval 1.32 to 4.34), anterior location (odds ratio = 0.25, 95% confidence interval 0.15 to 0.42), and age (odds ratio = 0.97, 95% confidence interval 0.95 to 0.99). Preprocedure Thrombolysis In Myocardial Infarction flow grade >0 was the only predictor of LV function recovery (odds ratio = 6.73, 95% confidence interval 2.69 to 16.88). In conclusion, this study showed no difference in LV function recovery in patients undergoing primary PCI treated either with abciximab or high-dose bolus tirofiban. Preprocedure Thrombolysis In Myocardial Infarction flow grade >0 seems to be the most important predictor of favorable LVEF and LV function recovery at 30 days.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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