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Pathogenic gene mutations are found in about 50% of patients with hypertrophic cardiomyopathy (HC). Previous studies have shown an association between sarcomere mutations and medium-term outcome. The association with long-term outcome has not been described. The aim of this cohort study was to assess the long-term outcomes of patients with genotype positive (G+) and genotype negative (G-) HC. The study population consisted of 626 patients with HC (512 probands and 114 relatives) who underwent phenotyping and genetic testing from 1985 to 2014. End points were all-cause mortality, cardiovascular (CV) mortality, heart failure (HF)-related mortality, and sudden cardiac death/aborted sudden cardiac death (SCD/aborted SCD). Kaplan-Meier and multivariate Cox regression analyses were performed. A pathogenic mutation was detected in 327 patients (52%). G+ probands were younger than G- probands (46 ± 15 vs 55 ± 15 years, p0.001), had more non sustained ventricular tachycardia (34% vs 13%; p0.001), more often a history of syncope (14% vs 7%; p = 0.016), and more extreme hypertrophy (maximal wall thickness ≥30 mm, 7% vs 1%; p0.001). G- probands were more symptomatic (New York Heart Association ≥II, 73% vs 53%, p0.001) and had higher left ventricular outflow tract gradients (42 ± 39 vs 29 ± 33 mm Hg, p = 0.001). During 12 ± 9 years of follow-up, G+ status was an independent risk factor for all-cause mortality (hazard ratio [HR] 1.90, 95% CI 1.14 to 3.15; p = 0.014), CV mortality (HR 2.82, 95% CI 1.49 to 5.36; p = 0.002), HF-related mortality (HR 6.33, 95% CI 1.79 to 22.41; p = 0.004), and SCD/aborted SCD (HR 2.88, 95% CI 1.23 to 6.71; p = 0.015). In conclusion, during long-term follow-up, patients with G+ HC are at increased risk of all-cause death, CV death, HF-related death, and SCD/aborted SCD.

The prognostic value of dobutamine stress echocardiography (DSE) at >10-year follow-up is unknown. The aim of this study was to assess the very long-term prognostic value of DSE in a high-risk cohort of patients with known or suspected coronary artery disease. This prospective, single-center study included 3,381 patients who underwent DSE from January 1990 to January 2003. Two-dimensional echocardiographic images were acquired at rest, during dobutamine stress, and during recovery. Follow-up events were collected and included overall mortality, cardiac death, nonfatal myocardial infarction, and revascularization. The incremental value of DSE in the prediction of selected end points was evaluated using multivariate Cox proportional hazard analysis. During a mean follow-up of 13 ± 3.2 years (range 7.3 to 20.5 years), there were 1,725 deaths (51%), of which 1,128 (33%) were attributed to cardiac causes. Patients with an abnormal DSE had a higher mortality rate (44% vs 35% at 15-year follow-up, p

Previous data have indicated that carotid plaque ulceration is a strong predictor of cerebrovascular events. Standard ultrasound and color Doppler ultrasound (CDUS) scans have poor diagnostic accuracy for the detection of carotid plaque ulceration. The aim of the present prospective study was to assess the value of contrast-enhanced ultrasound (CEUS) scans for the detection of carotid plaque ulceration. The Institutional Ethics Committee approved the study protocol, and all patients provided informed consent. The patients had symptomatic stenosis of the internal carotid artery and underwent carotid computed tomographic angiography as part of their clinical evaluation. All patients underwent a CDUS examination in conjunction with CEUS. Carotid plaque ulceration was defined as the presence of >= 1 disruptions in the plaque-lumen border >= 1 x 1 mm. Carotid computed tomographic angiography was used as reference technique. The study population consisted of 20 patients (mean age 64 +/- 9 years, 80% men), and 39 carotid arteries were included in the present analysis. Computed tomographic angiography demonstrated that the plaque surface was smooth in 15 (38%), irregular in 7 (18%) and ulcerated in 17 (44%) carotid arteries. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CDUS for the detection of ulceration was 29%, 73%, 54%, 46%, and 57%, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CEUS for the detection of ulceration was 88%, 59%, 72%, 63%, and 87%, respectively. CEUS had superior sensitivity and diagnostic accuracy for the assessment of carotid plaque ulceration compared with CDUS. CEUS improved the intrareader and inter-reader variability for the assessment of carotid plaque ulceration compared with CDUS. In conclusion, CEUS could be an additional method for the detection of carotid plaque ulceration. The role of CDUS for the assessment of carotid plaque ulceration seems limited. (C) 2013 Elsevier Inc. All rights reserved.

Cardiovascular risk stratification of asymptomatic patients is based on the assessment of risk factors. Noninvasive imaging of subclinical atherosclerosis may improve cardiovascular risk stratification, especially in patients with co-morbidities. The aim of this study was to investigate the effect of contrast-enhanced ultrasound (CEUS) of the carotid arteries on cardiovascular risk assessment. The study population consisted of 100 consecutive asymptomatic patients with >= 1 clinical risk factor for atherosclerosis. Cardiovascular risk was estimated by calculating the Prospective Cardiovascular Munster Heart Study (PRO-CAM) risk score. This score was divided into 3 subgroups: low (= 20%). Subclinical carotid atherosclerosis was assessed using standard ultrasound for intima-media thickness and plaque screening and CEUS for additional plaque screening. CEUS was performed using SonoVue contrast agent. Patients with subclinical atherosclerosis were considered to be at high cardiovascular risk. McNemar's test was used to compare PROCAM score to ultrasound findings. The mean PROCAM risk score was 9 +/- 10; the PROCAM risk score was low in 72 patients (72%), intermediate in 17 patients (17%), and high in 11 patients (11%). A total of 21 patients (21%) had abnormal carotid intima-media thickness, 77% had plaques on conventional carotid ultrasound, and 88% had plaques on standard carotid ultrasound combined with CEUS. Detection of atherosclerosis led to the reclassification of 79 patients (79%) to high cardiovascular risk (p

The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration = 120 ms, respectively (p = 120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >= 120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:1490-1493)

Previous studies have shown a good outcome for patients who present with normal findings on stress myocardial perfusion imaging. Currently, the prognostic implications of a normal study in patients who have a history of coronary artery disease (CAD) are not clear. This study investigated the long-term prognosis after a normal finding on stress technetium-99m (Tc-99m)-tetrofosmin single-photon emission computed tomography in patients with a history of CAD. The study included 147 consecutive patients with a history of CAD (previous myocardial infarction and/or myocardial revascularization), who underwent exercise bicycle or high-dose dobutamine-atropine stress Tc-99m-tetrofosmin single-photon emission computed tomography, and had normal perfusion results during stress and at rest. Follow-up was completed in all patients. During a follow-up of 6.5 +/- 1.9 years, 20 patients (14%) died, 10 (7%) of whom died due to cardiac causes, and 12 (8%) had a nonfatal myocardial infarction. Annual cardiac death rates were 0.5% during the first 3 years of follow-up and 1.3% in the subsequent 3 years. Independent predictors of cardiac death were male gender, rate-pressure product at rest, and rate-pressure product at peak stress. In conclusion, patients who have a history of CAD have a very low cardiac death rate during the 3 years after a normal finding on stress Tc-99m-tetrofosmin single-photon emission computed tomography. Repeated testing should be reconsidered 3 years after the initial evaluation and when a change in symptoms or clinical condition occurs.

This study assessed the incidence, clinical correlates, and prognostic significance of angina during dobutamine stress echocardiography (DSE) in patients who did not have inducible wall motion abnormalities. We studied 2,117 patients (61 +/- 13 years of age; 1,149 men) who underwent large-dose DSE and had no new or worsening wall motion abnormalities during DSE. Follow-up events were hard cardiac events (cardiac death or nonfatal myocardial infarction) and myocardial revascularization. Angina was induced in 217 patients (10%) during stress. DSE was normal in 1,198 patients (57%), whereas 919 patients (43%) had fixed wall motion abnormalities. During a mean follow-up of 5.5 +/- 3.7 years, 143 patients (7%) died of cardiac causes and 78 (4%) had nonfatal myocardial infarction. Patients who developed angina during DSE were more likely to have a history of exertional angina (64% vs 16%, p0.001) and had a higher wall motion score index at rest (1.29 +/- 0.5 vs 1.17 +/- 0.4, p = 0.01) compared with patients who did not have angina. Annual hard cardiac event rates were 2.2% in patients who had dobutamine-induced angina (DIA) and 2.1% in patients who did not (p = NS). Myocardial revascularization was performed more frequently in patients who had DIA than in those who did not (39% vs 14%, p0.0001). In Cox's regression model, independent predictors of hard events were age (RR 1.03, 95% confidence interval [CI] 1.02 to 1.04), male gender (RR 1.6, 95% CI 1.1 to 2.2), smoking (RR 1.5, 95% CI 1.1 to 2.9), and wall motion score index at rest (RR 2.6, 95% CI 1.8 to 3.8). In conclusion, in patients who do not have ischemia by echocardiographic criteria during DSE, inducible angina pectoris is associated with a high incidence of revascularization during follow-up. However, the hard cardiac event rate does not differ in patients who develop DIA from those who do not.

This study assessed the effect of ischemia during dobutamine stress echocardiography (DSE) on cardiac mortality in patients with heart failure. We studied 528 patients (62 +/- 11 years of age, 402 men) who had heart failure and previous myocardial infarction or known coronary artery disease and underwent DSE. Ischemia was defined as new or worsening wall motion abnormalities or a biphasic response. End point during follow-up was cardiac death. Mean ejection fraction was 35 +/- 12%. Ischemia was detected in 407 patients (77%). During a mean follow-up of 3.2 +/- 2.4 years, cardiac death occurred in 150 patients (28%). Myocardial revascularization was performed within 4 months after DSE in 117 patients (29%) who had ischemia. Annual rates of cardiac death were 4.8% in patients who did not have ischemia, 5.5% in those who had ischemia and underwent revascularization within 4 months, and 11.8% in those who had ischemia and were not revascularized (p0.001 vs other groups). In a multivariate analysis model, independent predictors of cardiac death were diabetes (RR 2, 95% confidence interval 1.4 to 2.9), male gender (RR 1.7, 95% confidence interval 1.2 to 3.1), low-dose wall motion score index (RR 1.4, 95% confidence interval 1.2 to 2.6), and ischemia (RR 1.9, 95% confidence interval 1.3 to 3.2). Angina was not predictive of death. In patients who had ischemia, revascularization within 4 months after DSE was associated with decreased risk of cardiac death (RR 0.43, 95% confidence interval 0.3 to 0.8). In conclusion, myocardial ischemia that is detected by DSE is associated with increased risk of cardiac death among patients who have heart failure, after adjustment for left ventricular function. Patients who had ischemia and received revascularization within 4 months had a better survival than did patients who had ischemia and did not receive revascularization. Angina had no effect on prognosis. Therefore, patients who do not have angina should not be considered a lower-risk population if they have inducible ischemia.

The presence of a right bundle branch block (RBBB) is associated with increased mortality. We studied the role of dobutamine stress echocardiography for the prognostic stratification of patients with RBBB. The presence of an abnormal dobutamine stress echocardiography was the strongest predictor of cardiac events and provided incremental prognostic information to clinical and stress test data.

Peri-infarction and remote myocardial ischemia involve different myocardial substrates, but their differential clinical implications have not been previously studied. We assessed the differential prognostic significance of peri-infarction and remote ischemia during long-term follow-up in patients with healed myocardial infarction. We studied 345 patients (59 +/- 12 years old; 282 men) with previous myocardial infarction who demonstrated reversible perfusion abnormalities on exercise or dobutamine stress technetium-99m sestamibi tomography. Follow-up events for 5.5 +/- 2.6 years were 60 deaths (17%; 40 cardiac deaths) and 25 reinfarctions (7%). Reversible perfusion abnormalities were detected in the remote region in 129 patients (37%), the peri-infarction region in 142 patients (41%), and in both regions in 74 patients (21%). The annual rates of cardiac death in these groups were 1.2%, 2.8%, and 2.9%, respectively (p0.01). The annual rates of reinfarction were 1%, 1.5%, and 0.9%, respectively (p = NS). In a multivariate analysis model, independent predictors of cardiac death were history of heart failure (risk ratio [RR] 2.8, 95% confidence interval [95% CI] 1.2 to 7), diabetes mellitus (RR 4.1, 95% CI 1.9 to 8.9), summed score at rest (RR 1.4, 95% CI 1.1 to 3.1), and peri-infarction ischemia (RR 2.6, 95% CI 1.1 to 6.1). Predictors of reinfarction were age (RR 1.03, 95% CI 1.01 to 1.07) and diabetes mellitus (RR 3.3, 95% CI 1.2 to 9.1). Peri-infarction ischemia assessed by stress technetium-99m sestamibi tomography is associated with a greater risk of cardiac death than is remote ischemia. The risk of reinfarction is not related to the location of ischemia.

Currently, there are no outcome data to suggest an incremental value of stress echocardiography in the risk stratification of patients who have hypertension after controlling for the left ventricular mass index (LVMI). This study assessed the incremental value of dobutamine stress echocardiography (DSE) for the prediction of mortality rate and cardiac events in patients who have hypertension. We studied 596 patients who had hypertension (mean age 62 ± 12 years; 382 men) and who underwent DSE for evaluation of known or suspected coronary artery disease. End points during follow-up were hard cardiac events (cardiac death and nonfatal myocardial infarction) and total mortality rate. Left ventricular hypertrophy was detected by echocardiography in 119 patients (20%). During a median follow-up of 3 years, 101 patients (17%) died (43 cardiac deaths) and 19 patients had nonfatal myocardial infarction. In an incremental multivariate analysis model, clinical predictors of hard cardiac events were age, history of congestive heart failure, and LVMI. The percentage of abnormal myocardial segments examined with DSE was incremental to the clinical model (chi square 41 vs 27, p

Technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomography (SPECT) is a useful alternative to thallium-201 scintigraphy for the assessment of myocardial perfusion. This study assessed the incremental value of exercise Tc-99m tetrofosmin SPECT for the prediction of cardiac events in patients with known or suspected coronary artery disease. Exercise Tc-99m tetrofosmin SPECT imaging was performed in 655 consecutive patients. Follow-up was successful in 648 patients (98.9%). Ten patients underwent early coronary revascularization and were excluded. End points were cardiac death, nonfatal infarction, and late (>60 days) coronary revascularization. An abnormal study was defined as the presence of fixed and/or reversible perfusion defects. A summed stress score (SSS) was derived to estimate the extent and severity of perfusion defects. An abnormal scan was detected in 344 patients (54%). During a mean follow-up period of 4 +/- 1.3 years, 56 patients (9%) died (22 cardiac deaths). Nonfatal myocardial infarction occurred in 19 patients (3%), and 89 patients (14%) underwent late coronary revascularization. An abnormal scan was an independent predictor of cardiac death (hazard ratio 3.5, confidence intervals [CI] 1.1 to 12.2) and provided incremental information over clinical and exercise test data (log-likelihood -133 to -125, p

Chronic electrocardiographic Q waves are often believed to reflect irreversibly scarred, transmurally infarcted myocardium. The aim of this study was to evaluate whether residual viable tissue persists in dysfunctional myocardial regions related to chronic Q waves on the surface electrocardiogram. A total of 148 patients with healed myocardial infarction and impaired left ventricular (LV) function with heart failure symptoms underwent electrocardiography and metabolic imaging using technetium (Tc-99m) tetrofosmin/F18-fluorodeoxyglucose (FDG) single-photon emission computed tomography (SPECT). The left ventricle was divided into 4 major regions to compare myocardial viability in regions with and without chronic Q waves on surface electrocardiography. According to FDG SPECT metabolic imaging, residual viable tissue persisted in a high proportion (61%) of dysfunctional myocardial regions with chronic Q waves. Regions with chronic Q waves were more often dysfunctional than regions without Q waves. Moreover, dysfunctional regions with chronic Q waves were less frequently viable compared with dysfunctional regions without Q waves on the electrocardiogram. This study demonstrates that chronic Q waves on electrocardiography do not necessarily imply irreversibly scarred myocardium. Residual viable tissue persists in a high proportion of dysfunctional ventricular regions according to FDG SPECT metabolic imaging.

Technetium-99m-tetrofosmin single-photon emission computed tomography at rest is practical for routine assessment of viability in patients with ischemic cardiomyopathy. However, underestimation of viability may occur compared with 18F-fluorodeoxyglucose single-photon emission computed tomography, especially in the inferoposterior and septal regions.