Nishimura, Rick A.

Background— Myocardial late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (CE-MRI) of patients with hypertrophic cardiomyopathy (HCM) has been suggested to represent intramyocardial fibrosis and, as such, an adverse prognostic risk factor. We evaluated the characteristics of LGE on CE-MRI and explored whether LGE among patients with HCM was associated with genetic testing, severe symptoms, ventricular arrhythmias, or sudden cardiac death (SCD). Methods and Results— Four hundred twenty-four patients with HCM (age=55±16 years [range 2 to 90], 41% females), without a history of septal ablation/myectomy, underwent CE-MRI (GE 1.5 Tesla). We evaluated the relation between LGE and HCM genes status, severity of symptoms, and the degree of ventricular ectopy on Holter ECG. Subsequent SCD and appropriate implanted cardioverter defibrillator (ICD) therapies were recorded during a mean follow-up of 43±14 months (range 16 to 94). Two hundred thirty-nine patients (56%) had LGE on CE-MRI, ranging from 0.4% to 65% of the left ventricle. Gene-positive patients were more likely to have LGE ( P <0.001). The frequencies of New York Heart Association class ≥3 dyspnea and angina class ≥3 were similar in patients with and without LGE (125 of 239 [52%] versus 94 of 185 [51%] and 24 of 239 [10%] versus 18 of 185 [10%], respectively, P =NS). LGE-positive patients were more likely to have episodes of nonsustained ventricular tachycardia (34 of 126 [27%] versus 8 of 94 [8.5%], P <0.001), had more episodes of nonsustained ventricular tachycardia per patient (4.5±12 versus 1.1±0.3, P =0.04), and had higher frequency of ventricular extrasystoles/24 hours (700±2080 versus 103±460, P =0.003). During follow-up, SCD occurred in 4 patients, and additional 4 patients received appropriate ICD discharges. All 8 patients were LGE positive (event rate of 0.94%/y, P =0.01 versus LGE negative). Two additional heart failure-related deaths were recorded among LGE-positive patients. Univariate associates of SCD or appropriate ICD discharge were positive LGE ( P =0.002) and presence of nonsustained ventricular tachycardia ( P =0.04). The association of LGE with events remained significant after controlling for other risk factors. Conclusions— In patients with HCM, presence of LGE on CE-MRI was common and more prevalent among gene-positive patients. LGE was not associated with severe symptoms. However, LGE was strongly associated with surrogates of arrhythmia and remained a significant associate of subsequent SCD and/or ICD discharge after controlling for other variables. If replicated, LGE may be considered an important risk factor for sudden death in patients with HCM.

Background— The clinical efficacy of alcohol septal ablation for drug-refractory hypertrophic cardiomyopathy remains unclear. This study examines the outcome of alcohol septal ablation performed at a tertiary hypertrophic cardiomyopathy referral center. Methods and Results— Among 601 patients with severely symptomatic obstructive hypertrophic cardiomyopathy referred for alcohol septal ablation or myectomy from 1998 to 2006, 138 patients (median age, 64 years; 39% men) chose to undergo ablation. Procedural complications included death in 1.4%, sustained ventricular arrhythmias in 3%, tamponade in 3%, and pacemaker implantation in 20%. This rate was higher than a combined complication rate of 5% in age- and gender-matched patients who had undergone septal myectomy at Mayo Clinic ( P <0.0001). Four-year survival free of all mortality was 88.0% (95% confidence interval, 79.4 to 97.5%), which was similar to that of the age- and gender-matched patients who had undergone myectomy ( P =0.18). Six patients had documented ventricular arrhythmias after ablation, 4 of whom had successful intervention. Four-year survival free of death and severe New York Heart Association class III/IV symptoms after septal ablation was 76.4%, and 71 patients (51%) became asymptomatic. Myectomy patients ≤65 years of age had significantly better survival free of death and severe symptoms ( P =0.01). Conclusions— Alcohol septal ablation is an efficacious procedure if performed in an experienced institution and may resolve symptoms in a subset of patients with obstructive hypertrophic cardiomyopathy. However, the procedural complication rate exceeds that of myectomy. Patients ≤65 years of age have better symptom resolution with myectomy. No impairment in short-term survival was noted in this nonrandomized study, but the long-term outcome remains unknown.

Background— Diastolic dysfunction is a major pathophysiological abnormality in hypertrophic cardiomyopathy (HCM). Doppler echocardiographic parameters correlate with left ventricular (LV) filling pressures in other diseases, but it is unclear whether these findings apply to patients with HCM, who have multiple complex interrelated events leading to diastolic dysfunction. This study compares Doppler echocardiographic estimates of filling pressures to direct measurements of left atrial pressure (LAP) via catheterization in 100 patients with HCM. Methods and Results— One hundred patients who were symptomatic with HCM (New York Heart Association class III/IV, 82%) underwent measurement of early diastolic transmitral flow velocity (E) and mitral annular velocities (e′) with the use of transthoracic echocardiography within 48 hours of cardiac catheterization with direct measurement of LAP. In a subset of 42 patients, echocardiographic and catheterization measurements were performed simultaneously. Mean LAP directly correlated with medial E-e′ ratio in the overall population ( r =0.44, P <0.0001) and also in the subgroup of patients who had simultaneous echocardiographic and catheterization studies ( r =0.28, P =0.07). However, scatter was present. A calculated mean LV filling pressure was derived from the E-e′ ratio with the use of a previously described regression equation, and the 95% confidence limits of agreement with measured mean LAP exceeded ±18 mm Hg both for the overall group and for the subgroup who had simultaneous studies. Similar results were obtained with the lateral E-e′ ratio. Only 1 patient had a previously defined “normal” E-e′ ratio of <8. Conclusions— In symptomatic patients with HCM, Doppler echocardiographic estimates of LV filling pressure with the use of transmitral flows and mitral annular velocities correlate modestly with direct measurement of LAP. Given the complex nature of diastolic dysfunction in HCM, precise characterization of LV filling pressure in an individual patient cannot be determined with the use of these noninvasive parameters.

Background The early diastolic velocity of the mitral annulus (E′) is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E′ has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E′ is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E′ and PCWP in patients with CP. Methods and Results We studied 10 patients (8 men; mean age, 64±7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E′. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E′ were 91±15 cm/s and 11±4 cm/s, respectively. Mean PCWP was 25±6 mm Hg. E′ was positively correlated with PCWP ( r =0.69, P =0.027). There was a significant inverse correlation between E/E′ and PCWP ( r =−0.74, P =0.014). Despite high left ventricular filling pressures, E/E′ (mean, 9±4) was <15 in all but 1 patient. Conclusions Paradoxical to the positive correlation between E/E′ and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.

Background— This study assessed the long-term outcome of a large, asymptomatic population with hemodynamically significant aortic stenosis (AS). Methods and Results— We identified 622 patients with isolated, asymptomatic AS and peak systolic velocity ≥4 m/s by Doppler echocardiography who did not undergo surgery at the initial evaluation and obtained follow-up (5.4±4.0 years) in all. Mean age (±SD) was 72±11 years; there were 384 (62%) men. The probability of remaining free of cardiac symptoms while unoperated was 82%, 67%, and 33% at 1, 2, and 5 years, respectively. Aortic valve area and left ventricular hypertrophy predicted symptom development. During follow-up, 352 (57%) patients were referred for aortic valve surgery and 265 (43%) patients died, including cardiac death in 117 (19%). The 1-, 2-, and 5-year probabilities of remaining free of surgery or cardiac death were 80%, 63%, and 25%, respectively. Multivariate predictors of all-cause mortality were age (hazard ratio [HR], 1.05; P <0.0001), chronic renal failure (HR, 2.41; P =0.004), inactivity (HR, 2.00; P =0.001), and aortic valve velocity (HR, 1.46; P =0.03). Sudden death without preceding symptoms occurred in 11 (4.1%) of 270 unoperated patients. Patients with peak velocity ≥4.5 m/s had a higher likelihood of developing symptoms (relative risk, 1.34) or having surgery or cardiac death (relative risk, 1.48). Conclusions— Most patients with asymptomatic, hemodynamically significant AS will develop symptoms within 5 years. Sudden death occurs in ≈1%/y. Age, chronic renal failure, inactivity, and aortic valve velocity are independently predictive of all-cause mortality.