2014 Volume 78 Issue 10 Pages 2501-2506
Background: The influence of the physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) is unclear. There have been no comprehensive studies of pregnant women with HCM in the Japanese population.
Methods and Results: A total of 27 pregnancies (23 women with HCM) were retrospectively reviewed. A total of 18 cardiovascular events occurred in 13 of the 27 pregnancies (48%), and 13 of these events (76%) were related to arrhythmia. The cardiovascular events tended to occur in the early stage of pregnancy (≈30 gestational weeks) or postpartum. The events related to arrhythmia mainly occurred in the early stage of pregnancy or at approximately 30 gestational weeks. Four pregnancies were terminated because of cardiovascular events. Cardiovascular events occurred in 8 of 9 pregnancies in women on medication before pregnancy (88%), 7 of 10 pregnancies with high CARPREG score (70%), and in 9 of 12 pregnancies with high ZAHARA score (75%).
Conclusions: Cardiovascular events occurred in more than half of the pregnant women complicated with HCM, and the arrhythmia is the most common cardiovascular event. Medication in the pre-pregnancy period, and CARPREG or ZAHARA score ≥1 were identified as risk factors of cardiac events during pregnancy or postpartum. (Circ J 2014; 78: 2501–2506)
Hypertrophic cardiomyopathy (HCM) is a disease that presents as cardiac muscle dilation with asymmetric diversity. The complications of HCM include arrhythmia, left ventricular outflow obstruction, and diastolic and partial systolic dysfunction because of the myocardial thickening. HCM may result in heart failure, thrombosis, atrial and ventricular arrhythmias, and sudden death, but is often asymptomatic. HCM is thought of as a rare disease, but a recent investigation showed a prevalence of approximately 1.8% in Japan, corresponding to an estimated 21,900 patients with HCM in Japan.1,2 Therefore, HCM may be more common than previously thought, and this is a matter of concern in the context of pregnancy.
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There are few reports on pregnancy in women with exacerbated cardiomyopathy, and the perinatal prognosis of this condition is unclear. The available reports include 7 studies of pregnancy with HCM.3–9 In the first of these studies, which examined 13 pregnancies with HCM, Turner et al found that vaginal birth was not possible in 2 cases because of worsening angina and in 1 because of breathing difficulties.3 Autore et al identified 98 survivors and 2 deaths during pregnancy among 100 women with HCM (199 pregnancies),5 giving a maternal mortality of 10 in 1,000 live births (95% confidence interval 1.1–36.2/1,000), which is higher than that in normal pregnancy. An investigation of the morbidity rate in 40 pregnancies with HCM showed deterioration in New York Heart Association cardiac performance (NYHA class) in 1 of 28 women who were asymptomatic before pregnancy, and in 5 of 12 women who were symptomatic, thus indicating that the perinatal prognosis is excellent in patients who are asymptomatic before becoming pregnant.5 In a comparison of nonpregnant and pregnant (n=23) women with HCM, the incidence of arrhythmia was higher in those who were pregnant (33.3% vs. 13.4%), but heart failure and cardiac infarction rates did not differ significantly.6 There were no deaths in either group, and pregnancy was assumed to have had no influence on the natural course of HCM. Cardiovascular events that required hospitalization increased when there was a family history (71.4% vs. 25.0%), which indicates the need to obtain a family medical history in the case of pregnancy with HCM.6
Pregnancy increases the circulating blood volume and cardiac output because of increases in the ventricular rate and stroke volume, while the peripheral vascular resistance decreases. The circulating blood volume increases more rapidly after 20 gestational weeks and reaches a plateau at 32 gestational weeks of 40–45% of the nonpregnant volume.10,11 In HCM, the preload increase, afterload decrease and increase in cardiac contraction are precipitating factors because the ventricular blood volume decreases and left ventricular outflow obstruction deteriorates. The influence of these pregnancy-related physiologic changes on the circulation in HCM is not well understood. Therefore, in this the first study of this condition in Japan, we investigated the cardiovascular events that occurred during pregnancy with HCM.
We examined the outcomes of 27 pregnancies (23 women with HCM) between 1995 and 2013 at the Department of Perinatology, National Cerebral and Cardiovascular Center, Japan. HCM was diagnosed using the definition and type classification of cardiomyopathy published by the World Health Organization/International Society and Federation of Cardiology Joint Committee in 1995, by a cardiovascular physician based on medical history, physical findings, ECG, chest X-rays, an echocardiogram, and Doppler ultrasound. Radionuclide scans, computed tomography, magnetic resonance imaging, a cardiac catheter test, coronary arteriography, myocardial biopsy, and genetic diagnosis were performed when necessary. HCM was subcategorized into hypertrophic nonobstructive cardiomyopathy (HNCM), hypertrophic obstructive cardiomyopathy (HOCM), and dilated phase of HCM (D-HCM) with systolic dysfunction such as left ventricular ejection fraction (LVEF) <50%.
Information on maternal background was collected, including age, parity, complications, medications before pregnancy, NYHA class before pregnancy, family history of HCM, echocardiographic parameters; maximum wall thickness, LVEF, left atrial diameter in endsystole (LADs), mitral regurgitation (MR), and the pressure gradient (PG) of the left ventricular outflow tract obstruction (LVOTO), CARPREG score12 and ZAHARA score13 were retrospectively calculated. The CARPREG score is a contemporary assessment of maternal and neonatal risks associated with pregnancy in women with heart disease who are receiving comprehensive prenatal care. Frequency of maternal primary cardiac events, as predicted by the risk index and observed in the derivation and validation groups, is expressed as a function of the number of cardiac predictors or points. The ZAHARA score is a modified risk score for cardiac complications during completed pregnancies in women with congenital heart disease.
Maternal and neonatal outcomes were examined, including cardiovascular events, NYHA class during pregnancy, NYHA class postpartum, gestational age, delivery mode, indication for cesarian section, birth weight, pH of the umbilical artery, and Apgar score at 5 min. Cardiovascular events were defined as new onset or worsening of arrhythmia, heart failure, endocarditis, or thromboembolic events that required medication, hospitalization, or termination of pregnancy. The gestational week of the occurrence of all cardiovascular events was recorded. Cardiovascular events were also classified as those related to arrhythmia or other than arrhythmia. The type of arrhythmia, gestational week of occurrence, and the detection method were recorded for each cardiovascular event related to arrhythmia.
Statistical AnalysisUnivariate analysis by chi-squared test and the Cochran-Armitage trend test was used for statistical analysis. P<0.05 was considered significant.
Maternal background data for the 27 pregnancies (23 women) with HCM are shown in Table 1. The median age was 32 years (21–39 years). The mother was nulliparous in 17 pregnancies (63%) and multiparous in 10 (48%). Cases 3 and 4, 12 and 13, 15 and 16, and 21 and 22 relate to the same woman in each pair of cases (4 women). There were 17 women with HNCM, 6 with HOCM, and none D-HCM. One woman was complicated with tetralogy of Fallot after repair. Other maternal complicating diseases were idiopathic thrombocytopenic purpura and Bartter syndrome in 1 woman each. The medications administered before pregnancy were verapamil in 3 women, diltiazem in 2 women, β-blocker in 6 women, mexiletine in 2 women and angiotensin-converting enzyme inhibitor in 1 woman. A family history of HCM was identified in 6 women (26%). The NYHA class before pregnancy was I in all except 1 woman in class II (case 10) and that woman had LADs >50 mm, moderate MR, and a PG of LVOTO >50 mmHg. Among the other women with HOCM, the PG of LVOTO before pregnancy or in early pregnancy was between 15 and 35 mmHg. Therefore, all of the patients, except for the woman in case 10, were in good general condition.
| Case no. |
Age (years) |
Parity | Complication | HOCM | D-HCM | Medication pre-pregnancy |
NYHA class (pre-pregnancy) |
LVEF <50% |
Family history |
LADs >50 mm |
MR ≥moderate |
LVOTO >50 mmHg |
Maximau wall thickness >30 mm |
ZAHARA score |
CARPREG score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 25 | 0 | TOF | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 2 | 25 | 0 | No | + | – | Metoprolol, Verapamil | 1 | – | – | – | – | – | – | 1.5 | 0 |
| 3 | 31 | 0 | ITP | – | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 4 | 33 | 1 | ITP | – | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 5 | 33 | 1 | – | – | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 6 | 32 | 2 | – | – | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 7 | 21 | 0 | Bartter syndrome | – | – | – | 1 | – | – | – | – | – | – | 1.5 | 0 |
| 8 | 32 | 0 | – | + | – | Verapamil | 1 | – | – | – | – | – | – | 3 | 1 |
| 9 | 39 | 0 | – | + | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 10 | 30 | 0 | – | + | – | Diltiazem | 2 | – | + | + | + | + | + | 4.75 | 1 |
| 11 | 33 | 1 | – | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 12 | 25 | 0 | – | + | – | Mexiletine, Metoprolol | 1 | – | – | – | – | – | – | 3 | 1 |
| 13 | 30 | 1 | – | + | – | Mexiletine, Metoprolol | 1 | – | – | – | – | – | – | 3 | 2 |
| 14 | 33 | 0 | – | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 15 | 32 | 0 | – | – | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 16 | 34 | 1 | – | – | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 17 | 32 | 0 | – | – | – | Propranolol | 1 | – | – | – | – | – | – | 3 | 1 |
| 18 | 32 | 0 | – | + | – | – | 1 | – | + | – | – | – | – | 0 | 0 |
| 19 | 33 | 0 | – | – | – | Diltiazem, Enalapril | 1 | – | – | – | – | – | – | 3 | 1 |
| 20 | 34 | 1 | – | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 21 | 29 | 0 | – | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 22 | 33 | 1 | – | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 23 | 31 | 1 | – | – | – | – | 1 | – | – | – | – | – | – | 0 | 0 |
| 24 | 27 | 0 | – | – | – | – | 1 | – | – | – | – | – | – | 1.5 | 1 |
| 25 | 33 | 0 | – | – | – | Propranolol | 1 | – | – | – | – | – | – | 3 | 1.5 |
| 26 | 35 | 1 | – | – | – | – | 1 | – | – | – | – | – | – | 1.5 | 1 |
| 27 | 28 | 0 | – | – | – | Propranolol, Verapamil | 1 | – | – | – | – | – | – | 3 | 1.5 |
D-DCM, dilated phase of hypertrophic cardiomyopathy (HCM); HOCM, hypertrophic obstructive cardiomyopathy; LADs, atrial diameter in endsystole; LVEF, left ventricular ejection fraction; LVOTO, left ventricular outflow tract obstruction; MR, mitral regurgitation; NYHA, New York Heart Association.
Maternal and neonatal outcomes for the 27 pregnancies (23 women) with HCM are shown in Tables 2,3. A total of 17 cardiovascular events occurred in 13 pregnancies (48%), including 13 events (76%) related to arrhythmia (Table 4). Arrhythmia was the most common cardiovascular event. The cardiovascular events occurred in the early stage of pregnancy at approximately 30 gestational weeks, or postpartum (Figure). The events related to arrhythmia mainly occurred in the early stage of pregnancy or at approximately 30 gestational weeks. A total of 4 pregnancies were terminated because of a cardiovascular event (cases 8, 10, 11, 12). In case 8, the pregnancy was terminated at 31 gestational weeks because the mother was developing pulmonary hypertension and the PG of LVOTO had increased rapidly (peak PG 57 mmHg). Postpartum, the PG returned to the pre-pregnancy value. In cases 10 and 11, pregnancy was terminated at 27 and 36 gestational weeks, respectively, because in both cases there was an increased PG of LVOTO resulting from increased preload, and the mothers developed lung edema. After termination, the lung edema improved in both cases. In case 12, the pregnancy was terminated because nonsustained ventricular tachycardia (NSVT) could not be controlled with drug therapy. Thus, 3 of the 4 pregnancies (75%) were terminated because of a cardiovascular event in the mother who had started or increased her dose of antiarrhythmic drugs.
| Case no. |
Cardiovascular event |
Gestational week |
NYHA class (pregnancy) |
NYHA class (postpartum) |
Gestational age (weeks) |
Delivery mode |
Indication of CS |
Birth weight (g) |
UA pH | APS (5 min) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | No | 1 | 1 | 36 | VD | 2,690 | 7.36 | 9 | ||
| 2 | Yes | 30 | 1 | 1 | 38 | VD | 2,822 | 7.33 | 9 | |
| 3 | Yes | 30 | 1 | 1 | 38 | CS | NRFS | 2,286 | 7.28 | 9 |
| 4 | Yes | 13 | 1 | 1 | 37 | CS | Previous CS | 2,940 | 7.35 | 9 |
| 5 | Yes | 32 | 1 | 1 | 40 | VD | 3,190 | 7.32 | 9 | |
| 6 | No | 1 | 1 | 38 | VD | 2,724 | 7.25 | 9 | ||
| 7 | Yes | 32 | 1 | 1 | 36 | VD | 2,426 | 7.31 | 9 | |
| 8 | Yes | 12, 31 | 1 | 1 | 31 | CS | Heart | 1,512 | 7.25 | 6 |
| 9 | No | 1 | 1 | 40 | VD | 3,016 | 7.32 | 9 | ||
| 10 | Yes | 13, 27 | 3 | 2 | 27 | CS | Heart | 850 | 7.29 | 5 |
| 11 | Yes | 32, 36 | 3 | 1 | 36 | CS | Heart | 2,250 | 7.21 | 7 |
| 12 | Yes | 13, 29 | 1 | 1 | 29 | CS | Heart | 1,013 | 7.33 | 3 |
| 13 | Yes | Postpartum | 1 | 1 | 37 | CS | Previous CS | 2,070 | 7.35 | 8 |
| 14 | No | 1 | 1 | 37 | VD | 2,326 | 7.24 | 10 | ||
| 15 | No | 1 | 1 | 39 | VD | 2,562 | 7.25 | 9 | ||
| 16 | No | 1 | 1 | 38 | VD | 3,124 | 7.38 | 10 | ||
| 17 | Yes | 31 | 1 | 1 | 39 | VD | 2,250 | 7.306 | 9 | |
| 18 | No | 1 | 1 | 37 | VD | 2,874 | 7.201 | 8 | ||
| 19 | Yes | Postpartum | 1 | 1 | 37 | VD | 2,533 | 7.26 | 9 | |
| 20 | No | 1 | 1 | 37 | VD | 3,364 | 7.35 | 9 | ||
| 21 | No | 1 | 1 | 38 | VD | 2,858 | 7.27 | 8 | ||
| 22 | No | 1 | 1 | 40 | VD | 3,054 | 7.29 | 8 | ||
| 23 | No | 1 | 1 | 39 | CS | Previous CS | 3,008 | 7.28 | 9 | |
| 24 | No | 1 | 1 | 34 | VD | 2,434 | 7.35 | 10 | ||
| 25 | Yes | 24 | 1 | 1 | 39 | CS | CPD | 3,994 | 7.34 | 9 |
| 26 | No | 1 | 1 | 37 | VD | 2,674 | 7.29 | 10 | ||
| 27 | Yes | Postpartum | 1 | 1 | 38 | VD | 2,646 | 7.27 | 8 |
CPD, cephalopelvic disproportion; CS, cesarean section; NRFS, non-reassuring fetal status; UA, umbilical artery; VD, vaginal delivery. Other abbreviations as in Table 1.
| Cardiovascular event | 14/27 (52%) |
| Termination of pregnancy because of cardiovascular event | 4/27 (15%) |
| Worsening of NYHA class during pregnancy | 2/27 (7%) |
| Preterm birth | 7/27 (26%) |
Abbreviations as in Table 1.
| Case no. | Type of arrhythmia | Period (week) | Correspondence | Antiarrhythmic drug | Dose (mg) |
|---|---|---|---|---|---|
| 2 | PVC | 30 | Antiarrhythmic drug started | Metoprolol | 30 |
| 3 | NSVT | 30 | Antiarrhythmic drug started | Metoprolol | 60 |
| 4 | NSVT | 13 | Antiarrhythmic drug started | Propranolol | 60 |
| 5 | NSVT | 32 | Antiarrhythmic drug started | Metoprolol | 40 |
| 7 | PVC, PAC | 32 | Antiarrhythmic drug started | Metoprolol | 40 |
| 8 | PVC | 12 | Antiarrhythmic drug started | Bisoprolol | 2.5 |
| 10 | PVC | 13 | Antiarrhythmic drug started | Propranolol | 60 |
| 11 | NSVT | 32 | Antiarrhythmic drug started | Atenolol | 25 |
| 12 | NSVT | 13 | Antiarrhythmic drug increased | Metoprolol | 40→60 |
| 12 | NSVT | 29 | CS | – | – |
| 17 | PVC | 31 | Antiarrhythmic drug started | Propranolol | 20 |
| 25 | VT | 24 | Antiarrhythmic drug started | Carvedilol | 10 |
| 27 | PVC | Postpartum | Antiarrhythmic drug increased | Propranolol | 60→80 |
NSVT, nonsustained ventricular tachycardia (VT); PAC, premature atrial contraction; PVC, premature ventricular contraction. Other abbreviations as in Tables 1,2.
Cardiovascular events and gestational weeks (n=18).
Premature delivery occurred in 7 of the 27 pregnancies (26%) because of cardiovascular events in 4 cases (57%) and obstetric complications (threatened premature labor) in 3 cases.
When comparing the pregnancies complicated by cardiovascular events with those unaffected by such events, the NYHA class before pregnancy, and echocardiographic parameters (LVEF, LADs, MR, LVOTO, maximum wall thickness) could not be analyzed because of the small number of positive findings. HOCM or family history of HCM were not risk factors (P=0.22, P=0.90). In the current study, medication in the pre-pregnancy period and CARPREG or ZAHARA score ≥1 or more were identified as risk factors of cardiac events during pregnancy or postpartum (Table 5).
| Cardiovascular events | P value | |
|---|---|---|
| HCM | ||
| No | 8/20 (40%) | NS |
| Yes | 5/7 (71%) | |
| D-HCM | ||
| No | 13/27 (48%) | NS |
| Yes | 0/0 (0%) | |
| Medication (pre-pregnancy) | ||
| No | 5/18 (28%) | <0.05 |
| Yes | 8/9 (88%) | |
| NYHA class (pre-pregnancy) | ||
| 1 | 12/26 (46%) | NS |
| ≥2 | 1/1 (100%) | |
| LVEF <50% | ||
| No | 13/27 (48%) | NS |
| Yes | 0/0 (0%) | |
| Family history | ||
| No | 9/19 (33%) | NS |
| Yes | 4/8 (50%) | |
| LADs >50 mm | ||
| No | 12/26 (46%) | NS |
| Yes | 1/1 (100%) | |
| MR ≥moderate | ||
| No | 12/26 (46%) | NS |
| Yes | 1/1 (100%) | |
| LVOTO >50 mmHg | ||
| No | 12/26 (46%) | NS |
| Yes | 1/1 (100%) | |
| Maximum wall thickness >30 mm | ||
| No | 12/26 (46%) | NS |
| Yes | 1/1 (100%) | |
| High CARPREG score | ||
| 0 | 6/17 (35%) | <0.05 |
| ≥1 | 7/10 (70%) | |
| High ZAHARA score | ||
| 0 | 4/15 (26%) | <0.05 |
| ≥1 | 9/12 (75%) | |
NS, not significant. Other abbreviations as in Table 1.
A cardiovascular event related to HCM occurred in 13 of 27 pregnancies. Cardiovascular events showed 3 peak times of occurrence: early pregnancy, approximately 30 gestational weeks, and postpartum. In previous similar studies,3–8 women who were symptomatic before pregnancy and who had a family history were at risk of cardiovascular events during their pregnancies. Our new findings are that risk factors of cardiovascular events were medication before pregnancy and higher CARPREG or ZAHARA score.
The frequency of cardiovascular events (48%) is similar to the 28–73% reported in previous studies.3–9 Collectively the findings show there is a high frequency of cardiovascular events in pregnancy for women with HCM. In the present study, 13 of the 18 events were related to arrhythmia, indicating that many of the cardiovascular events in pregnancy with HCM involve arrhythmia. Mostly, it was ventricular arrhythmias, including premature ventricular contraction and NSVT, and in some cases they were not controllable by medication, which is unusual. These findings indicate the importance of recognizing arrhythmia as a probable cardiovascular event in a pregnant woman with HCM.
Cardiovascular events occurred most frequently at approximately 30 gestational weeks. The increase in the circulating blood volume at 32 gestational weeks reaches 40–45% of the nonpregnant level, and it is notable that the most frequent period of cardiovascular events coincided approximately with the period of peak circulating blood volume during pregnancy. In 3 of the 4 pregnancies terminated because of a cardiovascular event, the event occurred during this period, which suggests that such cases require strict management and medication in the early stage of pregnancy.
Medication before pregnancy and higher CARPREG or ZAHARA score were risk factors for experiencing a cardiovascular event during pregnancy. However, further accumulation of cases and a study of multiple factors are required. These additional factors should include the general condition of the HCM patient, which appeared to influence the outcome in this study, and the observations from previous studies, which include an excellent perinatal prognosis in patients who are asymptomatic before pregnancy,5 family history,8 the apparent lack of influence of pregnancy on the natural course of HCM, and the tendency for a good prognosis when no symptoms are present before pregnancy.7 Consideration of the timing of cardiovascular events may also be included in this analysis, given our finding of a high frequency of cardiovascular events in the early stage of pregnancy, at approximately 30 gestational weeks, and postpartum. Medication in the pre-pregnancy period, and CARPREG or ZAHARA score ≥1 were identified as risk factors of cardiac events during pregnancy or postpartum. However, this study was a retrospective analysis with the limitations of a small number of patients and the rarity of the condition.
If a pregnant woman with HCM has such factors as medication in the pre-pregnancy period or CARPREG or ZAHARA score ≥1, careful observation for cardiovascular events is required, especially at approximately 12 and 30 weeks’ gestation and also postpartum.
