Heidi M. Connolly

Valvular heart disease associated with fenfluramine phentermine

BACKGROUND Fenfluramine and phentermine have been individually approved as anorectic agents by the Food and Drug Administration (FDA). When used in combination the drugs may be just as effective as either drug alone, with the added advantages of the need for lower doses of each agent and perhaps fewer side effects. Although the combination has not been approved by the FDA, in 1996 the total number of prescriptions in the United States for fenfluramine and phentermine exceeded 18 million. METHODS We identified valvular heart disease in 24 women treated with fenfluramine-phentermine who had no history of cardiac disease. The women presented with cardiovascular symptoms or a heart murmur. As increasing numbers of these patients with similar clinical features were identified, there appeared to be an association between these features and fenfluramine-phentermine therapy. RESULTS Twenty-four women (mean [+/-SD] age, 44+/-8 years) were evaluated 12.3+/-7.1 months after the initiation of fenfluramine-phentermine therapy. Echocardiography demonstrated unusual valvular morphology and regurgitation in all patients. Both right-sided and left-sided heart valves were involved. Eight women also had newly documented pulmonary hypertension. To date, cardiac surgical intervention has been required in five patients. The heart valves had a glistening white appearance. Histopathological findings included plaque-like encasement of the leaflets and chordal structures with intact valve architecture. The histopathological features were identical to those seen in carcinoid or ergotamine-induced valve disease. CONCLUSIONS These cases arouse concern that fenfluramine-phentermine therapy may be associated with valvular heart disease. Candidates for fenfluramine-phentermine therapy should be informed about serious potential adverse effects, including pulmonary hypertension and valvular heart disease.

Ebstein's anomaly.

Ebstein’s anomaly is a rare congenital heart disorder occurring in 1 per 200 000 live births and accounting for 1% of all cases of congenital heart disease.2–6 This anomaly was described by Wilhelm Ebstein in 1866 in a report titled, “Concerning a very rare case of insufficiency of the tricuspid valve caused by a congenital malformation.” 7,8 The patient was a 19-year-old cyanotic man with dyspnea, palpitations, jugular venous distension, and cardiomegaly. 7,8 At autopsy, Ebstein described an enlarged and fenestrated anterior leaflet of the tricuspid valve. The posterior and septal leaflets were hypoplastic, thickened, and adherent to the right ventricle. There was also a thinned and dilated atrialized portion of the right ventricle, an enlarged right atrium, and a patent foramen

Severe aortic stenosis with low transvalvular gradient and severe left: ventricular dysfunction: Result of aortic valve replacement in 52 patients

BACKGROUND The outcome of aortic valve replacement in patients with severe aortic stenosis, low transvalvular gradient, and severe left ventricular dysfunction is not well known. METHODS AND RESULTS Between 1985 and 1995, 52 patients with left ventricular ejection fraction (EF) < or =35% and aortic stenosis with transvalvular mean gradient <30 mm Hg underwent aortic valve replacement. The mean (+/-SD) preoperative characteristics included EF, 26+/-8%; aortic valve mean gradient, 23+/-4 mm Hg; aortic valve area, 0.7+/-0.2 cm(2); and cardiac output, 3.7+/-1.2 L/min. Simultaneous coronary artery bypass graft surgery was performed in 32 patients (62%). Perioperative (30-day) mortality was 21% (11 of 52 patients). Ten additional patients died during follow-up. Advanced age (P=0.048) and small aortic prosthesis size (P=0.03) were significant predictors of hospital mortality by univariate analysis. By multivariate analysis, the only predictor of surgical mortality was smaller prosthesis size. The only predictor of postoperative survival was improvement in postoperative functional class (P=0.04). Postoperative functional improvement occurred in most patients. Postoperative EF was assessed in 93% of survivors; 74% demonstrated improvement. Positive change in EF was related to smaller preoperative aortic valve area and female sex. CONCLUSIONS Despite severe left ventricular dysfunction, low transvalvular mean gradient, and increased operative mortality, aortic valve replacement was associated with improved functional status. Postoperative survival was related to younger patient age and larger aortic prosthesis size, and medium-term survival was related to improved postoperative functional class.

Aortic Valve Replacement for Aortic Stenosis With Severe Left Ventricular Dysfunction Prognostic Indicators

BACKGROUND Aortic valve replacement for aortic stenosis (AS) carries an increased risk in the presence of left ventricular (LV) systolic dysfunction. Few data are available on the outcome of such patients. METHODS AND RESULTS Between 1985 and 1992, 154 consecutive patients (107 men and 47 women) with LV systolic dysfunction (ejection fraction [EF] < or = 35%) underwent aortic valve replacement for AS. The mean preoperative characteristics included EF, 27 +/- 6%; aortic valve mean gradient, 44 +/- 18 mm Hg; aortic valve area, 0.6 +/- 0.2 cm2; and cardiac output, 4.1 +/- 1.5 L/min. Simultaneous coronary artery bypass graft surgery was performed in 78 patients (51%). Perioperative (30-day) mortality was 9% (14 of 154 patients). Fifty patients died during follow-up. Coronary artery disease (P = .002) and a reduced preoperative cardiac output (P = .03) were significantly related to reduced overall survival rate by multivariate analysis. Postoperative improvement occurred in most patients; 88% were New York Heart Association class III or IV before surgery versus 7% after surgery. Postoperative EF was assessed in 76% of survivors; 76% of these demonstrated improvement. By multivariate analysis, change in EF was inversely related to coronary disease (P = .002) and preoperative aortic valve area (P = .03). CONCLUSIONS Despite LV dysfunction, the risk of aortic valve replacement for AS was acceptable and related to coronary artery disease and mean aortic gradient, and long-term survival was related to coronary disease and cardiac output. Improvement in symptoms and EF occurred in most patients.

Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function: The clinical utility of the dobutamine challenge in the catheterization laboratory

Background—Although aortic valve replacement can be performed at an acceptable risk level in selected patients with left ventricular systolic dysfunction and low-output, low-gradient aortic stenosis, not all patients presenting with these hemodynamics will benefit from the operation. Some patients may have only mild aortic stenosis, despite a small calculated valve area. We report on the clinical utility of diagnostic dobutamine stimulation during cardiac catheterization in these diagnostically challenging patients. Methods and Results—Thirty-two patients with low-output, low-gradient aortic stenosis and an ejection fraction <40% had dobutamine infusion in the catheterization laboratory. On the basis of the results of the dobutamine test, 21 patients underwent aortic valve replacement. All patients with a final aortic valve area ≤1.2 cm2 at peak dobutamine infusion and a mean gradient of >30 mm Hg were found to have severe calcific aortic stenosis at operation. In the 15 patients in whom contractile reserve was identified during dobutamine challenge (increase in stroke volume >20%), 1 patient died perioperatively (7% mortality) and 12 patients were alive in New York Heart Association class I or II status at follow-up. Conclusions—In patients with left ventricular systolic dysfunction and aortic stenosis with a low output and a low mean gradient, dobutamine challenge may aid in selecting those who would benefit from an aortic valve operation.

Valvular Heart Disease in Patients Taking Pergolide

OBJECTIVE To determine whether an association exists between pergolide and valvular heart disease. PATIENTS AND METHODS Three patients with severe, unexplained tricuspid regurgitation were examined at our institution from September 2000 to April 2002. Echocardiography and histology of surgically explanted valves revealed abnormalities suggestive of carcinoid involvement, methysergide or ergotamine treatment, or use of fenfluramine and dexfenfluramine. Carcinoid valvular heart disease was excluded. None of the patients had prior treatment with these drugs. All 3 patients were taking pergolide. RESULTS Of the 3 patients, 2 had predominantly right-sided congestive heart failure. In all 3 patients, echocardiography showed unusual valve morphology, with severe tricuspid valve regurgitation. Significant left-sided valve regurgitation was noted in 2 patients. Histologic analysis revealed surface fibroproliferative lesions with preserved underlying valve architecture. CONCLUSION The echocardiographic and histopathologic features of these cases are strikingly similar to those associated with carcinoid-, ergot-, and fenfluramine-induced valve disease. An association between pergolide and valvular heart disease may therefore exist.

Coarctation of the aorta: outcome of pregnancy☆

OBJECTIVES The study sought to determine the outcome of pregnancy in women with coarctation of the thoracic aorta. BACKGROUND Patients with coarctation of the thoracic aorta are expected to reach childbearing age, but data on the outcome of pregnancy in this population are limited. METHODS The Mayo Clinic database was reviewed for women of childbearing age (> or =16 years old) with a diagnosis of aortic coarctation evaluated from 1980 to 2000. Spectrum of cardiovascular disease, surgical history, and obstetrical and neonatal outcomes were determined. RESULTS Fifty women with coarctation had pregnancies: 30 had coarctation repair before pregnancy, 10 had repair after pregnancy, 4 had repair both before and after pregnancy, and 6 had no history of repair. The 50 women had 118 pregnancies resulting in 106 births. There were 11 miscarriages (9%), 4 premature deliveries (3%), and 1 early neonatal death; 38 deliveries (36%) were by cesarean section. Of the 109 offspring, 4 (4%) had congenital heart disease. A patient with Turner syndrome died of a Stanford type A dissection at 36 weeks of pregnancy. Nineteen women (38%) were known to have hemodynamically significant coarctation during pregnancy (gradient > or =20 mm Hg). Fifteen women (30%) had hypertension during their pregnancy, 11 of whom (73%) had hemodynamically significant coarctation during that time (8 with native and 3 with residual/recurrent coarctation). CONCLUSIONS Major cardiovascular complications were infrequent but continue to be a source of concern for patients with coarctation who become pregnant. Systemic hypertension during pregnancy was common and related to the presence of a significant coarctation gradient.

Best Practices in Managing Transition to Adulthood for Adolescents With Congenital Heart Disease: The Transition Process and Medical and Psychosocial Issues: A Scientific Statement From the American Heart Association

Many children born with complex childhood illnesses that historically caused early death are now surviving into adulthood with the expectation of leading meaningful and productive lives. They will ultimately need to transition their care from pediatric to adult-centered care. Unfortunately, in the absence of structured programs to guide this transition, there is often delayed or inappropriate care, improper timing of the transfer of care, and undue emotional and financial stress on the patients, their families, and the healthcare system. At its worst, and as frequently happens now, patients are lost to appropriate follow-up. In fact, the number of adults with congenital heart disease (CHD) in the United States is rising exponentially and now exceeds 1 000 000.1,–,7 At least half of these patients may have complex CHD. Fewer than 30% of adults with CHD are seen by appropriate specialized providers. Fewer than 15% of these patients, who are seen in specialty adult CHD (ACHD) clinics, have CHD that is classified as severe.8 Thus, adolescents with CHD constitute a growing population of individuals for whom a well-planned and well-executed “transition process” is essential. The goals of a formal transition program are to prepare young adults for transfer of care. It should provide uninterrupted health care that is patient centered, age and developmentally appropriate, flexible, and comprehensive. It should include age-appropriate education about medical conditions and promote skills in communication, decision making, self-care, and self-advocacy.9,–,13 It should foster greater personal and medical independence and a greater sense of control over health, healthcare decisions, and psychosocial environment. The ultimate goal of a transition program is to optimize the quality of life (QOL), life expectancy, and future productivity of young patients.14 We acknowledge that the development of ideal transition programs is a …

Noncompaction of the Ventricular Myocardium

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis. The characteristic echocardiographic findings consist of multiple, prominent myocardial trabeculations and deep intertrabecular recesses communicating with the left ventricular cavity. The disease uniformly affects the left ventricle, with or without concomitant right ventricular involvement, and results in systolic and diastolic ventricular dysfunction and clinical heart failure. Noncompaction was initially described in children. However, recent studies have characterized this disease in the adult population, in whom this process may be more prevalent than currently appreciated. We describe an illustrative case of isolated noncompaction of the ventricular myocardium in a 57-year-old woman with the typical clinical and echocardiographic features of the disease. The literature on the topic is reviewed.

Prognosis of Carcinoid Heart Disease: Analysis of 200 Cases Over Two Decades

Background— The long-term prognosis of patients who develop carcinoid heart disease and the effect of cardiac surgery on outcome are not well established. Methods and Results— In this retrospective study, we identified 200 patients with carcinoid syndrome referred for echocardiography in whom the diagnosis of carcinoid heart disease was confirmed. Patients were divided into 3 groups of similar size according to the date from first diagnosis of carcinoid heart disease. Group A comprised patients diagnosed from 1981 through June 1989; group B, diagnosed July 1989 through May 1995; and group C, June 1995 through 2000. The end point was all-cause mortality. Median survival was significantly lower in group A (1.5 years, 95% CI 1.1 to 1.9 years) compared with groups B (3.2, 95% CI 1.3 to 5.1 years) and C (4.4, 95% CI 2.4 to 7.1 years; P=0.009). In a multivariate model adjusted for treatment and clinical characteristics, the risk of death in groups B (hazard ratio 0.67, 95% CI 0.46 to 0.99, P=0.04) and C (hazard ratio 0.61, 95% CI 0.39 to 0.92, P=0.006) was significantly reduced relative to group A. Cardiac surgery was performed in 87 patients. When cardiac surgery was included as a time-dependent covariate in a multivariate analysis, it was associated with a risk reduction of 0.48 (95% CI 0.31 to 0.73, P<0.001), whereas the time period of diagnosis was no longer significant. Conclusions— The prognosis of patients with recognized carcinoid heart disease has improved over the past 2 decades at our institution. This change in survival may be related to valve replacement surgery.