Khandheria, Bijoy K.

BACKGROUND The carcinoid syndrome is a rare cause of acquired valvular heart disease. Although the typical echocardiographic features of carcinoid heart disease are well recognized, this large series provides new information about unusual manifestations of the disease as well as the role of Doppler echocardiography. METHODS AND RESULTS Between 1980 and 1989, 132 patients with carcinoid syndrome underwent echocardiographic study. The echocardiographic, Doppler, and clinical features of the 74 patients (56%) with echocardiographic evidence of carcinoid heart disease are described. Among these patients, 97% had shortened, thickened tricuspid leaflets. Tricuspid regurgitation was present in all 69 patients with carcinoid heart disease who underwent Doppler examination, and it was of moderate or severe degree in 62 patients (90%). Severe tricuspid regurgitation was characterized by a dagger-shaped Doppler spectral profile with an early peak pressure and rapid decline. The pressure half-time was prolonged (mean, 116 msec), which is consistent with associated tricuspid stenosis. The pulmonary valve appeared thickened, retracted, and immobile in 36 patients (49%) and was diminutive to the extent of not being visualized in an additional 29 patients (39%). Among the 47 patients who underwent Doppler evaluation of the pulmonary valve, regurgitation was present in 81%, and stenosis was present in 53%. Left-sided valvular involvement was present in five patients (7%), four of whom had patent foramen ovale or carcinoid tumor involving the lung. Previously undescribed myocardial metastases were present in three patients (4%) and were confirmed by biopsy in each case. Small pericardial effusions were present in 10 patients (14%). Patients with and without echocardiographic evidence of carcinoid heart disease did not differ with regard to sex, age, location of the primary tumor, duration of diagnosis, or duration of symptoms of carcinoid syndrome. However, the mean pretreatment level of urinary 5-hydroxyindoleacetic acid was higher in patients with carcinoid heart disease than in patients without carcinoid heart disease (270 versus 131 mg/24 hrs, p < 0.001). The symptom of dyspnea was more prevalent among patients with carcinoid heart disease than in patients without the disease (54% versus 27%, p = 0.003); as expected, heart murmurs were also noted more frequently in patients with disease (92% versus 43%, p < 0.0001). Treatment regimens and response to therapy were similar in the two groups. Survival of patients with echocardiographic evidence of carcinoid heart disease was reduced compared with those without cardiac involvement (p = 0.0003). ECG and chest roentgenographic findings in patients with carcinoid heart disease were nonspecific. CONCLUSIONS The broad spectrum of carcinoid heart disease is detailed in this large series. This includes not only right-sided valvular lesions but also left-sided involvement, pericardial effusion, and myocardial metastases.

Background and Purpose —There is little population-based information on cerebrovascular events and survival among valvular heart disease patients. We used the Kaplan-Meier product-limit method and the Cox proportional hazards model to determine rates and predictors of cerebrovascular events and death among valve disease patients. Methods —This population-based historical cohort study in Olmsted County, Minnesota, reviewed residents with a first echocardiographic diagnosis of mitral stenosis (n=19), mitral regurgitation (n=528), aortic stenosis (n=140), and aortic regurgitation (n=106) between 1985 and 1992. Results —During 2694 person-years of follow-up, 98 patients developed cerebrovascular events and 356 died. Compared with expected numbers, these observations are significantly elevated, with standardized morbidity ratio of 3.2 (95% CI, 2.6 to 3.8) and 2.5 (95% CI, 2.2 to 2.7), respectively. Independent predictors of cerebrovascular events were age, atrial fibrillation, and severe aortic stenosis. The risk ratio of severe aortic stenosis was 3.5 (95% CI, 1.4 to 8.6), with atrial fibrillation conferring greater risk at younger age. Predictors of death were age, sex, cerebrovascular events, ischemic heart disease, and congestive heart failure, the greatest risk being among those with both congestive heart failure and cerebrovascular events (risk ratio=8.8; 95% CI, 5.8 to 13.4). Valve disease type and severity were not independent determinants of death. Conclusions —The risk of cerebrovascular events and death among patients with valve disease remains high. Age, atrial fibrillation, and severe aortic stenosis are independent predictors of cerebrovascular events, and age, sex, cerebrovascular events, congestive heart failure, and ischemic heart disease are independent predictors of death in these patients.

Background and Purpose The purpose of this study was to clarify whether mitral valve prolapse increases the subsequent risk of stroke. Methods A historical cohort study was conducted on 1079 residents of Olmsted County, Minnesota, who had an initial echocardiographic diagnosis of mitral valve prolapse between 1975 and 1989 without prior stroke or transient ischemic attack and who were followed up for first stroke occurrence. Results There was an overall twofold increase in the incidence of stroke among individuals with mitral valve prolapse relative to the reference population (standardized morbidity ratio, 2.1; 95% confidence interval, 1.3 to 3.2). Sex, duration of follow-up from the diagnosis of mitral valve prolapse, or calendar year of initial diagnosis did not modify the association. Within the cohort of patients who were at least 35 years old at diagnosis of mitral valve prolapse, a time-dependent proportional-hazards multivariate model and a person-years analysis revealed that age, ischemic heart disease, congestive heart failure, and diabetes mellitus were important determinants for stroke when person-years of observation after mitral valve replacement were excluded. Among seven persons with mitral valve replacement, three strokes occurred in 24 person-years of follow-up. For those with an auscultatory diagnosis of mitral valve prolapse only as the indication for echocardiography (44%), the risk of stroke relative to the population was 1.0 (95% confidence interval, 0.2 to 2.9); for those with another cardiac diagnosis, the standardized morbidity ratio was 2.5 (95% confidence interval, 1.5 to 4.0). Conclusions Individuals with uncomplicated mitral valve prolapse did not have an increased risk of stroke, although a small increase in the risk may not have been detected.

Learning Objectives Analyze the clinical trial data for the treatment of breast cancer. Evaluate the risk of cardiotoxicity associated with the use of trastuzumab. Design and conduct a practical approach to managing patients with trastuzumab-associated cardiotoxicity. This article is available for continuing medical education credit at CME.TheOncologist.com.

Patients with hypertension exhibit impaired energetic coupling between the ventricle and the arterial system, leading to reduced cardiac mechanic efficiency and exercise capacity. We tested whether blood pressure normalization with current antihypertensive therapy can improve arterioventricular coupling. Eighteen hypertensive patients without other cardiovascular disease were examined before and after antihypertensive therapy. Transthoracic echocardiography was performed. Central aortic pressure waveforms, including end-systolic pressure, were derived from radial artery applanation tonometry. Afterload was increased with isometric handgrip exercise. Central aortic end-systolic pressure and ventricular volumes at rest and handgrip were used to calculate ventricular elastance, effective arterial elastance, arterioventricular coupling (effective arterial elastance/ventricular elastance), and mechanical efficiency. After 142±67 days, systolic blood pressure decreased from 150.9±14.6 to 119.8±9.2 mm Hg ( P <0.00001), diastolic blood pressure from 85.9±14.8 to 68.8±8.4 mm Hg ( P =0.00002), and cardiac output from 5.8±1.7 to 4.9±1.8 L/min ( P =0.03). Resting left ventricular end-systolic volume, ejection fraction, and septal thickness did not change. Ventricular elastance increased from 1.7±1.0 to 3.2±1.4 mm Hg/mL ( P =0.00002), whereas effective arterial elastance decreased from 1.4±0.5 to 1.2±0.4 mm Hg/mL ( P =0.02). Effective arterial elastance/ventricular elastance decreased in all patients, from 1.1±0.8 to 0.4±0.2 ( P =0.0002). Efficiency improved at rest (72.9±5.8% versus 83.5±5.7%; P <0.00001) and during handgrip (63.5±7.8% versus 78.9±7.1%; P <0.00001). In hypertensive patients, optimal brachial and central blood pressure reduction shifts arterioventricular coupling from cardiac output maximization to ventricular mechanical efficiency optimization. This occurs before significant changes in ventricular geometry and may be responsible for early clinical improvements.