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Effect of Left Ventricular Outflow Tract Obstruction on Clinical Outcome in Hypertrophic Cardiomyopathy

Martin Maron et al.Jan 22, 2003

The influence of left ventricular outflow tract obstruction on the clinical outcome of hypertrophic cardiomyopathy remains unresolved.We assessed the effect of outflow tract obstruction on morbidity and mortality in a large cohort of patients with hypertrophic cardiomyopathy who were followed for a mean (+/-SD) of 6.3+/-6.2 years.Of the 1101 consecutive patients, 273 (25 percent) had obstruction of left ventricular outflow under basal (resting) conditions with a peak instantaneous gradient of at least 30 mm Hg. A total of 127 patients (12 percent) died of hypertrophic cardiomyopathy, and 216 surviving patients (20 percent) had severe, disabling symptoms of progressive heart failure (New York Heart Association [NYHA] functional class III or IV). The overall probability of death related to hypertrophic cardiomyopathy was significantly greater among patients with outflow tract obstruction than among those without obstruction (relative risk, 2.0; P=0.001). The risk of progression to NYHA class III or IV or death specifically from heart failure or stroke was also greater among patients with obstruction (relative risk, 4.4; P<0.001), particularly among patients 40 years of age or older (P<0.001). Age-adjusted multivariate analysis confirmed that outflow tract obstruction was independently associated with an increased risk of both death related to hypertrophic cardiomyopathy (relative risk, 1.6; P=0.02) and progression to NYHA class III or IV or death from heart failure or stroke (relative risk, 2.7; P<0.001). The likelihood of severe symptoms and death related to outflow tract obstruction did not increase as the gradient increased above the threshold of 30 mm Hg.In patients with hypertrophic cardiomyopathy, left ventricular outflow tract obstruction at rest is a strong, independent predictor of progression to severe symptoms of heart failure and of death.

Epidemiology of Hypertrophic Cardiomyopathy–Related Death

Barry Maron et al.Aug 22, 2000

Background —Death resulting from hypertrophic cardiomyopathy (HCM), particularly when sudden, has been reported to be largely confined to young persons. These data emanated from tertiary HCM centers with highly selected referral patterns skewed toward high-risk patients. Methods and Results —The present analysis was undertaken in an international population of 744 consecutively enrolled and largely unselected patients more representative of the overall HCM spectrum. HCM-related death occurred in 86 patients (12%) over 8±7 years (mean±SD). Three distinctive modes of death were as follows: (1) sudden and unexpected (51%; age, 45±20 years); (2) progressive heart failure (36%; age, 56±19 years); and (3) HCM-related stroke associated with atrial fibrillation (13%; age, 73±14 years). Sudden death was most common in young patients, whereas heart failure– and stroke-related deaths occurred more frequently in midlife and beyond. However, neither sudden nor heart failure–related death showed a statistically significant, disproportionate age distribution ( P =0.06 and 0.5, respectively). Stroke-related deaths did occur disproportionately in older patients ( P =0.002). Of the 45 patients who died suddenly, most (71%) had no or mild symptoms, and 7 (16%) participated in moderate to severe physical activities at the time of death. Conclusions —HCM-related cardiovascular death occurred suddenly, or as a result of heart failure or stroke, largely during different phases of life in a prospectively assembled, regionally based, and predominantly unselected patient cohort. Although most sudden deaths occurred in adolescents and young adults, such catastrophes were not confined to patients of these ages and extended to later phases of life. This revised clinical profile suggests that generally held epidemiological tenants for HCM have been influenced considerably by skewed reporting from highly selected populations. These data are likely to importantly affect risk stratification and treatment strategies importantly for the prevention of sudden death in HCM.

Impact of Atrial Fibrillation on the Clinical Course of Hypertrophic Cardiomyopathy

Iacopo Olivotto et al.Nov 20, 2001

Clinical impact of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is largely unresolved. Thus, we analyzed the prognostic implications of AF in a large, community-based HCM population assembled from Italian and US cohorts.Occurrence of AF and outcome were assessed in 480 consecutive HCM patients (age at diagnosis, 45+/-20 years; 61% male) who were followed up for 9.1+/-6.4 years. AF occurred in 107 patients (22%; incidence, 2%/y) and was independently predicted by advancing age, congestive symptoms, and increased LA size at diagnosis. Patients with AF had increased risk for HCM-related death (OR, 3.7; P<0.002) because of excess heart failure-related mortality but not sudden, unexpected death. This risk associated with AF was substantially greater in patients with outflow obstruction or with earlier development of AF (

Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis of Hypertrophic Cardiomyopathy

Carsten Rickers et al.Aug 8, 2005

Two-dimensional echocardiography is currently the standard test for the clinical diagnosis of hypertrophic cardiomyopathy (HCM). The present study was undertaken to determine whether cardiac MRI (CMR) affords greater accuracy than echocardiography in establishing the diagnosis and assessing the magnitude of left ventricular (LV) hypertrophy in HCM.Forty-eight patients (age 34+/-16 years) suspected of having HCM (or with a confirmed diagnosis) were imaged by both echocardiography and CMR to assess LV wall thickness in 8 anatomic segments (total n=384 segments) and compared in a blinded fashion. Maximum LV thickness was similar by echocardiography (21.7+/-9.1 mm) and CMR (22.5+/-9.6 mm; P=0.21). However, in 3 (6%) of the 48 patients, echocardiography did not demonstrate LV hypertrophy, and CMR identified otherwise undetected areas of wall thickening in the anterolateral LV free wall (17 to 20 mm), which resulted in a new diagnosis of HCM. In the overall study group, compared with CMR, echocardiography also underestimated the magnitude of hypertrophy in the basal anterolateral free wall (by 20+/-6%; P=0.001), as well as the presence of extreme LV wall thickness (> or =30 mm) in 10% of patients (P<0.05).CMR is capable of identifying regions of LV hypertrophy not readily recognized by echocardiography and was solely responsible for diagnosis of the HCM phenotype in an important minority of patients. CMR enhances the assessment of LV hypertrophy, particularly in the anterolateral LV free wall, and represents a powerful supplemental imaging test with distinct diagnostic advantages for selected HCM patients.

Assessment of Diastolic Function With Doppler Tissue Imaging to Predict Genotype in Preclinical Hypertrophic Cardiomyopathy

Carolyn Ho et al.Jun 25, 2002

Background — Unexplained left ventricular hypertrophy (LVH) is considered diagnostic of hypertrophic cardiomyopathy (HCM) but fails to identify all genetically affected individuals. Altered diastolic function has been hypothesized to represent an earlier manifestation of HCM before the development of LVH; however, data regarding the clinical utility of imaging techniques that assess this parameter are limited. Methods and Results — Echocardiographic studies including Doppler tissue imaging (DTI) were performed in a genotyped HCM population with β-myosin heavy chain (β -MHC) mutations. Genotype (+) individuals with LVH (G+/LVH+; n=18) and genotype (+) individuals without LVH (G+/LVH−; n=18) were compared with normal control subjects (n=36). Left ventricular ejection fraction (EF) was significantly higher in both genotype (+) groups (75±5% and 71±6%, respectively, versus 64± 5% in control subjects; P <0.0001). Mean early diastolic myocardial velocities (Ea) were significantly lower in both genotype (+) subgroups, irrespective of LVH ( P <0.02). However, there was substantial overlap in Ea velocities between the G+/LVH− and control groups. An Ea velocity of ≤13.5 cm/s had 86% specificity and 75% sensitivity for identifying genotype-positive subjects. The combination of EF ≥68% and Ea velocity <15 cm/s was 100% specific and 44% sensitive in predicting affected genotype. Conclusions — Abnormalities of diastolic function assessed by Doppler tissue imaging precede the development of LVH in individuals with HCM caused by β -MHC mutations. Although Ea velocity alone was not sufficiently sensitive as a sole diagnostic criterion, the combination of Ea velocity and EF was highly predictive of affected genotype in individuals without overt manifestations of HCM.

Gender-Related Differences in the Clinical Presentation and Outcome of Hypertrophic Cardiomyopathy

Iacopo Olivotto et al.Jul 6, 2005

The goal of this study was to assess gender-related differences in a multicenter population with hypertrophic cardiomyopathy (HCM). Little is known regarding the impact of gender on the heterogeneous clinical profile and clinical course of HCM. We studied 969 consecutive HCM patients from Italy and the U.S. followed over 6.2 ± 6.1 years. Male patients had a 3:2 predominance (59%), similar in Italy and the U.S. (p = 0.24). At initial evaluation, female patients were older and more symptomatic than male patients (47 ± 23 years vs. 38 ± 18 years; p < 0.001; mean New York Heart Association [NYHA] functional class 1.8 ± 0.8 vs. 1.4 ± 0.6; p < 0.001), and more frequently showed left ventricular outflow obstruction (37% vs. 23%; p < 0.001). Moreover, female patients were less often diagnosed fortuitously by routine medical examination (23% vs. 41% in male patients, p < 0.001). Female gender was independently associated with the risk of symptom progression to NYHA functional classes III/IV or death from heart failure or stroke compared with male gender (independent relative hazard 1.5; p < 0.001), particularly patients ≥50 years of age and with resting outflow obstruction (p < 0.005). Hypertrophic cardiomyopathy-related mortality and risk of sudden death were similar in men and women. Women with HCM were under-represented, older, and more symptomatic than men, and showed higher risk of progression to advanced heart failure or death, often associated with outflow obstruction. These gender-specific differences suggest that social, endocrine, or genetic factors may affect the diagnosis and clinical course of HCM. A heightened suspicion for HCM in women may allow for timely implementation of treatment strategies, including relief of obstruction and prevention of sudden death or stroke.

Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy

Mark Sherrid et al.Apr 1, 2005

In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM). It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort. Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide. Patients were followed with disopyramide for 3.1 ± 2.6 years; dose 432 ± 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 ± 33 to 40 ± 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 ± 0.7 to 1.7 ± 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08). Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over ≥3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.