Systematic review of pregnancy in women with inherited cardiomyopathies

Summary

The authors review the literature on pregnancy in patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left-ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy. Physiological changes during normal pregnancy include a substantial increase of blood volume (by 40%) and in cardiac output. The heart rate increases about 10-15 beats per minute. Hormonal factors cause vasodilation early in pregnancy and remodeling of placental vessels in the second trimester result in marked decrease in systemic vascular resistance and lowering the blood pressure by about 10 mmHg. Pregnancy is also a hypercoagulable state. In labour, uterine contractions increase venous return and after delivery the amount of increase in cardiac output depends on the balance between blood loss and autotransfusion from uterus and placenta. During pregnancy drug absorption and metabolism is altered leading to higher concentrations of unbound drugs in the blood.

The authors state, that the following issues should be considered, ideally before the pregnancy: the specific underlying cardiac disease and its severity, effects on pregnancy on the disease and effects of the disease on the unborn child, medication during pregnancy, the possibility of palliative or corrective procedures, life expectancy and ability to care for a child and the risk of heart disease in the offspring.

Treatment options and safety of drug treatment of systolic heart failure during pregnancy are discussed. Cardiac arrhythmias and conduction disorders may occur during pregnancy. Pre-pregnancy arrhythmic events are predictive of recurrence during pregnancy. The authors underline that treatment is only indicated in those arrhythmias, which could endanger both mother and child. Safety on antiarrhythmic drug treatment is reviewed. Evidence on the safety of ICD devices and therapy is limited. In a single retrospective analysis of 44 patients ICD therapy was no risk for the mother or foetus and pregnancy did not increase ICD-related complications. Pregnancy induces a hypercoaguable state and thus patients with severe heart failure or arrhythmias require proper anticoagulation. Vitamin K antagonists cause embryopathy during the first trimester and on the other hand treatment with unfractionated or low-molecular-weight heparin is complicated. Several anticoagulation strategies have been published on anti-thmbotic therapy during pregnancy. The authors recommend that a plan for delivery should be made no later that the beginning of third trimester, taking into account obstetrical and cardiac factors. Spinal and epidural anaesthesia may cause hemodynamic instability and are relatively contraindicated in patients with HOCM whereas general anaesthesy or slow titration of epidural anaestesia, in specific situations, were considered relatively safe. HCM is the most common cardiomyopathy. It is important to identify patients with high risk of SCD, to treat arrhythmias and heart failure. Reduced venous return because of expulsive effort, blood loss and left ventricular outflow tract obstruction may pose a danger to HCM patients. Reported maternal deaths concern mainly high risk patients. Pregnancy in patients with asymptomatic or mild dilated cardiomyopathy (DCM) seems to be well tolerated. However pregnant women with DCM experience more adverse events than non-pregnant women with DCM. Predictors of adverse maternal events include moderate or severe left ventricular dysfunction and or NYHA functional class III or IV. Eleven cases of pregnancy in patients with ARVC have been reported. These suggest a favourable outcome in asymptomatic patients treated with optimal medical therapy.

There is a possibility that the risk of disease manifestation is increased during the third trimester and after delivery. The authors advise that ARVC patients with ventricular arrhythmias or (right-sided) heart failure should not become pregnant. Left ventricular non-compaction cardiomyopathy (LVNC) is often familial. LVNC by itself has an increased risk of thromboembolic complications and, according to the authors, warrants adequate anti-coagulation during pregnancy. There is limited evidence in the managing of LVNC in general or during pregnancy. Patients with functional NYHA class III or IV, sustained ventricular arrhythmias or enlarged left atrium have an unfavourable prognosis. There is little clinical data and no recommendations on the treatment available to guide clinicians in managing patients with restrictive cardiomyopathy (RCM). The authors suggest controlling the physiological factors which affect ventricular relaxation. They advise symptomatic patients with RCM not to become pregnant. Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure towards the end of pregnancy or in the first few months after delivery. Familial occurrence has been described. In many cases of PPCM normalization of left ventricular function may take place within the next 3-24 months. However, if the EF is below 25%, chances are reduced. Persisting left ventricular dysfunction increases the risk of heart failure, premature deliveries and maternal mortality (up to 19%) during subsequent pregnancies.

The authors concluded that pregnancy exposes patients with inherited cardiomyopathies to risks such as arrhythmias and heart failure. Pregnancy is generally well tolerated in asymptomatic patients with inherited cardiomyopathies. Prior cardiac events, poor functional class (New York Heart Association class III or IV), or advanced left ventricular dysfunction predict increased risk of maternal complications. The postpartum condition is generally no worse than the antepartum condition but there is a lack of long-term follow-up  studies. Preconception evaluation and counseling are recommended and the authors recommend genetic counselling and DNA testing to all women following the diagnosis of an inherited cardiomyopathy.

Comments

This review draws attention to the growing number of patients who need cardiac and obstetric evaluation and follow-up and genetic counseling. The authors stress the importance of planned management before and during pregnancy as well as during and after delivery. However, the number of studies on this topic is astonishingly low and treatment is sofar mostly based on general therapeutic principles. Larger prospective studies in specific types of cardiomyopathies would be needed to provide data on the clinical course of the disease and treatment in these patients during pregnancy.