Mohammed W. Akhter

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.

Pregnancy-Associated Cardiomyopathy Clinical Characteristics and a Comparison Between Early and Late Presentation

Background—Cardiomyopathy associated with pregnancy was first described more than half a century ago. However, because of its rare occurrence and geographical differences, the clinical profile of this condition has remained incompletely defined. Methods and Results—Data obtained from 123 women with a history of cardiomyopathy diagnosed during pregnancy or the postpartum period were reviewed. One hundred women met traditional criteria of peripartum cardiomyopathy; 23 were diagnosed with pregnancy-associated cardiomyopathy earlier than the last gestational month. Peripartum cardiomyopathy patients had a mean age of 31±6 years and were mostly white (67%). Common associated conditions were gestational hypertension (43%), tocolytic therapy (19%), and twin pregnancy (13%). Left ventricular ejection fraction at the time of diagnosis was 29±11% and improved to 46±14% (P≤0.0001) at follow-up. Normalization of left ventricular ejection fraction occurred in 54% and was more likely in patients with left ventricular ejection fraction >30% at diagnosis. Maternal mortality was 9%. A comparison between the peripartum cardiomyopathy and early pregnancy-associated cardiomyopathy groups revealed no differences in age, race, associated conditions, left ventricular ejection fraction at diagnosis, its rate and time of recovery, and maternal outcome. Conclusions—This study helps to define the clinical profile of patients with pregnancy-associated cardiomyopathy diagnosed in the United States. Clinical presentation and outcome of patients with pregnancy-associated cardiomyopathy diagnosed early in pregnancy are similar to those of patients with traditional peripartum cardiomyopathy. These 2 conditions may represent a continuum of a spectrum of the same disease.

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.

Intravenous Nitroglycerin in the Treatment of Decompensated Heart Failure: Potential Benefits and Limitations:

Acute decompensated heart failure (ADHF) is a common cause of hospitalizations. Intravenous nitroglycerin is widely used in the treatment of this condition. The use of this drug is based on its nitric oxide-mediated vasodilatory effect, which can lead to beneficial hemodynamic effects as well as improvement of myocardial ischemia and reduction of mitral regurgitation. However, information regarding the use of nitroglycerin for ADHF is limited to mostly hemodynamic evaluations in small groups of patients without cardiovascular outcome data. A single randomized, placebo controlled study that evaluated commonly used doses of nitroglycerin in patients with ADHF was disappointing and failed to show a significant hemodynamic effect or improvement of symptoms compared with placebo. The potential benefit of nitroglycerin seems to be limited by a decreased vasodilatory response in patients with heart failure, which requires an active titration of the drug and the use of high doses (>120 µg/min). In addition, the initial beneficial hemodynamic effect achieved with the appropriate dose of nitroglycerin is associated with neurohumoral activation and limited by an early development of nitrate tolerance that leads to a marked attenuation of the initial effect. More information obtained in large-scale studies that are appropriately designed to evaluate the effect of variable doses of nitroglycerin on short- and long-term cardiovascular outcome, with and without interventions shown to prevent nitrate tolerance, is needed before intravenous nitroglycerin can be recommended as a standard therapy for ADHF.

Anticoagulation in pregnant women with prosthetic heart valves

Background: Pregnancy is associated with an increased risk of thrombosis in women with mechanical prosthetic heart valves. Effective anticoagulation is therefore critical in such patients but remains problematic, since oral anticoagulation and both unfractionated and low-molecular-weight heparin may be associated with important fetal and maternal side effects. Purpose: To review information related to the use of anticoagulation with both warfarin and heparin and reassess the safety and efficacy of these therapies in pregnant women with mechanical prosthetic heart valves. Data source and selection: A MEDLINE search from 1966 to October 2003 for English and non-English language articles that reported the use of anticoagulation in pregnancy was conducted. Articles were included if they reported use of anticoagulation in pregnancy with emphasis on those that included women with mechanical prosthetic heart valves. Conclusions: Anticoagulation prophylaxis with both warfarin and heparin (unfractionated heparin and low-molecular-weight heparin) may be associated with important fetal and maternal side effects. Optional regimens for the treatment of low-risk and high-risk patients are proposed to minimize potential complications.

Nesiritide: a new drug for the treatment of decompensated heart failure.

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.

Variable Response of Conductance and Resistance Coronary Arteries to Endothelial Stimulation in Patients With Heart Failure Due to Nonischemic Dilated Cardiomyopathy

Attenuation of endothelial-dependent coronary vasodilation has been reported in idiopathic dilated cardiomyopathy and anatomically normal coronaries; however, data are insufficient for understanding the incidence and extent of this finding. The response of conductance and resistance coronary arteries to endothelial stimulation with acetylcholine was examined in 25 patients. Coronary blood flow had a variable response to acetylcholine and suggested coronary endothelial dysfunction in approximately half of the patients. Abnormal endothelial dysfunction involved the large conductance epicardial coronary arteries and the small resistance vessels. Abnormal endothelial response of coronary blood flow to acetylcholine could not be predicted by demographic and hemodynamic data. Conclusions: Coronary artery endothelial function is heterogeneous in patients with idiopathic dilated cardiomyopathy. Endothelial dysfunction is present in approximately half of the cases and involves both resistance as well as conductance coronary blood vessels. Furthermore, coronary endothelial function cannot be predicted by demographic and hemo-dynamic parameters or left ventricular ejection fraction.

Actualización clínica en valvulopatías

Durante los ultimos anos se han publicado en diferentes revistas de cardiologia multiples articulos relativos a los avances que han tenido lugar en el area de las valvulopatias. El objetivo de este comentario editorial es el de ofrecer al cardiologo general una revision comentada de los articulos mas importantes. El lector que desee detalles adicionales puede encontrarlos en 3 articulos publicados recientemente1-3. En el area de los procesos celulares y neurohormonas, en distintos estudios de investigacion recientes en los que se han evaluado los mecanismos celulares subyacentes a las valvulopatias degenerativas se ha observado que hay un proceso de osificacion endocondral que da lugar a la expresion de cartilago en las valvulas mitrales mixomatosas y a la expresion de hueso en las valvulas aorticas (VA) calcificadas. La degeneracion valvular se debe al engrosamiento iniciado por un proceso de diferenciacion osteoblastica mediado por la via de la senal de la proteina relacionada con el receptor de las lipoproteinas de densidad baja (Lrp5)4. En otros estudios se han demostrado la neoangiogenesis y el incremento en la expresion del gen de la proteina de golpe de calor hsp 60 en VA calcificadas y con estenosis en fase terminal, procesos no detectados en las valvulas de control5. Las determinaciones de peptidos natriureticos en 130 pacientes con estenosis aortica severa demostraron la presencia de concentraciones elevadas asociadas con el incremento de la clase funcional de la New York Heart Association (NYHA), la disminucion de la fraccion de eyeccion ventricular izquierda y el aumento de la gravedad de la enfermedad6. No obstante, es necesario determinar el valor clinico adicional de estas determinaciones.

Update in the Clinical Management of Valvular Heart Disease

In recent years a number of articles reflecting advances in the field of heart valvulopathies have been published in different cardiology journals. The aim of this editorial comment is to provide the general cardiologist with an annotated overview of the main ones. For additional details the reader is referred to 3 recent articles.1-3 Concerning the area of cellular processes and neurohormones, recent research into defining cellular mechanisms for degenerative valvular disease revealed that an endochondral bone process expresses cartilage in myxomatous mitral valves and bone in the calcified aortic valves (AV). Valve degeneration occurs due to thickening from an osteoblastic differentiation process mediated by the low-density lipoprotein receptor-related protein (Lrp5) signaling pathway.4 Other studies have shown neoangiogenesis and increased heat shock protein hsp 60 gene expression in end-stage calcified stenotic AV that was not present in control valves.5 Natriuretic peptide measurements in 130 patients with severe aortic stenosis demonstrated higher levels with increasing New York Heart Association (NYHA) functional classes, decreasing left ventricular ejection fraction and increasing severity of disease.6 The additional clinical value of these measurements needs to be determined.

Evaluation of myocardial blood flow reserve in patients with chronic congestive heart failure due to non-ischemic cardiomyopathy

Evaluation of Myocardial Blood Flow Reserve in Patients with Chronic Congestive Heart Failure Due to Non-Ischemic Cardiomyopathy Mohammed W. Akhter, Menahem Canetti, Amir Lerman, Ilyas S. Karaalp, Jason A. Zell, Harpreet Singh, Anilkumar Mehra, Uri Elkayam1—Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA; Division of Cardiovascular Medicine & Internal Medicine, Mayo Clinic Rochester, Rochester, MN