The effect of valvular heart disease on maternal and fetal outcome of pregnancy.

OBJECTIVES: The aim of this study was to evaluate the association between valvular heart disease (VHD) and maternal and fetal outcome in a relatively large group of patients by a comparison to a well-matched control group. BACKGROUND: Available information regarding outcome of pregnancy in women with VHD is limited to either anecdotal reports or small series of patients without an appropriate control. A better understanding of the effects of valvular abnormalities on pregnancy outcome is of value for risk assessment and the design of a therapeutic plan. METHODS: A retrospective evaluation was made of 66 pregnancies in 64 women with VHD cared for at a tertian-care center with a high-risk obstetrics/cardiology clinic and 66 individually selected normal pregnant women matched in age, ethnicity, obstetrical and medical history, time of initial prenatal care, and year of pregnancy. RESULTS: Women with VHD had a significantly higher incidence of congestive heart failure (38% vs. 0%; p < 0.00001), arrhvthmias (15% vs. 0%, p = 0.002), initiation or increase of cardiac medications (41% vs. 2%, p < 0.0001), and hospitalizations (35% vs. 2%, p < 0.0001). Mortality, however, occurred in only one patient (2% vs. 0%, p = NS) with aortic stenosis (AS) and coarctation. Moreover, VHD also had an effect on fetal outcome, resulting in an increased preterm delivery (23% vs. 6%, p = 0.03), intrauterine growth retardation (21% vs. 0%, p < 0.0001), and a reduced birth weight (2,897 +/- 838 g vs. 3,366 +/- 515 g, p = 0.0003). Increased maternal morbidity and unfavorable fetal outcome were seen mostly in patients with moderate and severe mitral stenosis (MS) and AS. CONCLUSIONS: Pregnancy in women with MS and AS is associated with marked increase in maternal morbidity and unfavorable effect on fetal outcome, which are related to severity of disease. Despite high maternal morbidity, mortality is rare.

Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy is a rare and sometimes fatal form of heart failure. Little is known about the outcomes of subsequent pregnancies in women who have had the disorder. METHODS: Through a survey of members of the American College of Cardiology, we identified 44 women who had had peripartum cardiomyopathy and had a total of 60 subsequent pregnancies. We then reviewed the medical records of these women and interviewed the women or their physicians. RESULTS: Among the first subsequent pregnancies in the 44 women, 28 occurred in women in whom left ventricular function had returned to normal (group 1) and 16 occurred in women with persistent left ventricular dysfunction (group 2). The pregnancies were associated with a reduction in the mean (+/-SD) left ventricular ejection fraction both in the total cohort (from 49+/-12 percent to 42+/-13 percent, P<0.001) and in each group separately (from 56+/-7 percent to 49+/-10 percent in group 1, P=0.002; and from 36+/-9 percent to 32+/-11 percent in group 2, P=0.08). During these pregnancies, a decrease of more than 20 percent in the left ventricular ejection fraction occurred in 21 percent of the women in group 1 and 25 percent of those in group 2, and symptoms of heart failure occurred in 21 percent of the women in group 1 and 44 percent of those in group 2. The mortality rate was 0 percent in group 1 and 19 percent in group 2 (P=0.06). In addition, the frequency of premature delivery was higher in group 2 (37 percent vs. 11 percent), as was that of therapeutic abortions (25 percent vs. 4 percent). CONCLUSIONS: Subsequent pregnancy in women with a history of peripartum cardiomyopathy is associated with a significant decrease in left ventricular function and can result in clinical deterioration and even death.

Unstable angina during pregnancy in two patients with premature coronary atherosclerosis and aortic stenosis in association with familial hypercholesterolemia.

Obstructive atherosclerotic coronary artery disease is uncommon in women during childbearing age, and the occurrence of myocardial ischemia during pregnancy has therefore been anecdotal. Two young patients with premature coronary artery disease in association with familial hypercholestrolemia had unstable angina in the second trimester of pregnancy. Workup revealed coronary artery disease and aortic stenosis. One patient opted for abortion at the twentieth week of gestation, and the other decided to continue pregnancy and was delivered by cesarean at 28 weeks' gestation. Coronary artery bypass grafting was performed after pregnancy in both patients. In addition, one of the patients underwent aortic valve replacement, and other had replacement of the narrowed ascending aorta with uneventful recovery. Our report describes an uncommon presentation of unstable angina during pregnancy in 2 young women with premature coronary artery disease and aortic valvular and supravalvular stenosis as a result of familial hypercholesterolemia. The management of these conditions during pregnancy is influenced by the effects of available therapeutic modalities on both maternal and fetal outcome.

The role of organic nitrates in the treatment of heart failure.

Nitrates have been widely used in the treatment of patients with chronic congestive heart failure. Although the use of these drugs has not been approved by the Food and Drug Administration, multiple studies have shown their favorable effects. Organic nitrates have been shown to have a beneficial effect on ischemia, hemodynamic profile, magnitude of a mitral regurgitation, endothelial function, and cardiac remodeling. These drugs, when used in combination with hydralazine, have improved exercise capacity and survival. Recent studies have shown that the use of nitrates in patients already treated with standard heart failure therapy, including angiotensin converting enzyme (ACE) inhibitors, resulted in hemodynamic improvement, marked enhancement of exercise tolerance, reduction of left ventricular size, and augmentation of systolic function. These data suggest a role for organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic heart failure and for nitrates in combination with hydralazine as an alternative treatment in patients who are intolerant to ACE inhibitors.

Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition.

BACKGROUND: Organic nitrates are widely used in the treatment of chronic heart failure (CHF). No information, however, is available regarding their effect in patients already treated with ACE inhibitors. METHODS AND RESULTS: In a randomized, double-blind, crossover design, we studied the effects of high-dose (50 to 100 mg) transdermal nitroglycerin (NTG) and placebo given daily for 12 hours in 29 patients with CHF (NYHA functional classes II to III). Exercise time (4 hours after patch application) showed a progressive improvement during NTG administration, with an increase of 38+/-35 seconds (9+/-7%) at the end of the first month (P=NS), 76+/-28 seconds (16+/-6%) at the end of the second month (P=0.01), and 117+/-34 seconds (27+/-6%) at the end of the third month (P=0.003). No significant change was seen during placebo administration (12+/-20, 5+/-26, and 19+/-28 seconds, all P=NS). Exercise time 8 hours after NTG application measured at 3 months was also significantly longer, with a difference of 87+/-28 seconds (P=0.006), but not with placebo (23+/-36 seconds, P=0.53). Assessment of quality of life and need for additional diuretics or hospitalizations for CHF failed to demonstrate a significant difference between the 2 treatment periods. In contrast, NTG decreased left ventricular end-diastolic (-2.1+/-0.1%, P<0.05) and end-systolic (-3.2+/-1.3%, P<0.05) dimensions and augmented LV fractional shortening (24.7+/-10.5%, P<0.03). The effect of placebo on these parameters was not statistically significant. CONCLUSION: High-dose nitrate therapy significantly improves exercise tolerance and left ventricular size and systolic function in patients with chronic, mild to moderate CHF already treated with ACE inhibitors. These findings support the role of organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic CHF.

Renal circulatory effects of adenosine in patients with chronic heart failure.

OBJECTIVES: We sought to study the renal circulatory effects of adenosine in patients with chronic congestive heart failure (CHF). BACKGROUND: Renal blood flow (RBF) is often reduced in patients with chronic CHF and may lead to decreased renal function. The cause of reduced RBF is multifactorial and involves systemic as well as local vasoregulatory mechanisms. Stimulation of renal adenosine A1 receptors in animal models has resulted in a significant vasoconstriction of afferent and efferent glomerular arterioles and deterioration of renal function. Although adenosine serum levels have been shown to be elevated in patients with CHF, their effect on the renal circulation in this patient population has not been studied. METHODS: Nine patients with CHF from left ventricular systolic dysfunction were studied. The effects of adenosine at a dose of 10(-5) mol/liter infused directly into the main renal artery on heart rate, renal artery blood pressure, renal artery cross-sectional area (measured by intravascular ultrasound), renal Doppler blood flow velocity (measured by a Doppler flow wire in the renal artery), RBF and renal vascular resistance (RVR) were evaluated. RESULTS: Infusion of adenosine resulted in no significant effect on heart rate or renal artery blood pressure but caused a substantial increase in RVR (11,204 +/- 1,469 to 31,494 +/- 3,911 dynes x s x cm(-5), p = 0.0005), which led to a marked fall in RBF in every patient (mean values 376 +/- 36 to 146 +/- 22 ml/m2, p = 0.0002). These changes in RVR and RBF were associated with no significant change in renal artery cross-sectional area (0.389 +/- 0.040 to 0.375 +/- 0.033 cm2, p = 0.3). CONCLUSIONS: Stimulation of renal adenosine receptors in patients with CHF results in marked renal vasoconstriction that leads to an important reduction in RBF. Lack of change in renal artery cross-sectional area suggests that adenosine affects intrarenal resistance blood vessels rather than large conductance vessels. These results may indicate a rationale for investigation of renal adenosine receptor blockade for enhancement of RBF and improvement of renal function in patients with chronic CHF.