Severe Subvalvular Aortic Stenosis in a Pregnant Woman.

A 35-year-old pregnant female in her second trimester presented with heart failure manifestations with evidence of very severe fixed left ventricular outflow tract obstruction. The peak systolic gradient was 132 mmHg, which is the highest reported in the literature, secondary to congenital subaortic membrane. Similar case reports that we could find in the literature were reviewed to highlight the importance of such anomaly. Copyright:

INTRODUCTION

Subvalvular aortic stenosis (SAS) also known as discrete subaortic stenosis is a congenital anomaly that causes left ventricular outflow tract (LVOT) obstruction. It is the second most common form of aortic stenosis (AS) and accounts for 6.5% of congenital heart disease in adults with a male predominance of 2:1. SAS may be crescent shaped, fibromuscular ridge, long tubular in shape, and fibrous subaortic ring; the latter may involve the anterior mitral leaflet. Sometimes, abnormal mitral chordae are infrequently reported to cause subaortic obstruction. In general, it is a silent disease that is rarely diagnosed in childhood and usually picked up after discovering a murmur. Furthermore, symptoms can be revealed during physical or hemodynamical stress such as pregnancy.[1]

Pregnancy is usually associated with major adaptive cardiovascular hemodynamic changes.[2] Intravascular volume is increased by 40% at 24 weeks of gestation, this leads to an increase in stroke volume, and later, the cardiac output is increased by 30%–50% from baseline. One-third of pregnant women develop reversible chamber enlargement. Heart rate is also increased by 10–30 beats per minute. Preload reduction occurs secondary to diminished venous return resulting from mechanical compression of the inferior vena cava by the gravid uterus. Furthermore, a substantial decrease of peripheral resistance in the placenta by circulating substances during pregnancy. Moreover, labor pain may aggravate LVOT obstruction in patients with SAS, AS, or hypertrophic cardiomyopathy.[3] Consequently, valvular heart disease encountered during pregnancy (~1%) can significantly increase both maternal and fetal risks.

According to the modified World Health Organization (WHO) classification of pregnancy risk, severe symptomatic AS represents a high risk of maternal mortality and severe maternal morbidity (WHO class IV). Patients in this group should be counseled against pregnancy, and termination should be discussed with the patient if pregnancy occurred.[2]

In addition, coexistence of cardiac obstructive lesions in pregnant women has a notorious effect on the fetus. The fetus may suffer from low birth weight, intracranial hemorrhage, or death.

Our patient is a young woman with severe symptomatic SAS due to congenital membrane causing severe fixed obstruction with very high intracavitary peak gradient exceeding 132 mmHg which is rarely encountered in literature reviews up to our knowledge.

CASE PRESENTATION

Our patient was a 35-year-old pregnant woman who was gravida 4, para 1 and experienced 2 abortions (in the first and second trimesters), her first pregnancy ended by spontaneous first-trimester miscarriage, her second pregnancy in 2013 was complicated by oligohydramnios, and she was diagnosed with LVOT obstruction due to SAS. In the third trimester, she underwent planned delivery by cesarean section 3 weeks before her expected date and she gave birth to a male healthy baby. In 2015, her third pregnancy was terminated at 16 weeks because of her cardiac condition and she underwent surgical evacuation after failed induction. Unfortunately, we do not have further details about that pregnancy.

The patient presented through the emergency department complaining of shortness of breath that started a few days before presentation, increased gradually in severity and duration, and worsen with moderate exertion. She denied symptoms of orthopnea or nocturnal dyspnea. The patient was pregnant in her 16th week of gestation despite the prior advice against pregnancy. She denied chest pain, productive cough, fever, hemoptysis, and dizziness and she had no abdominal pain, vaginal bleeding, or other cardiorespiratory or genitourinary symptoms. The patient's medications were aspirin 100 mg once daily and folic acid 5 mg daily.

On examination, she was afebrile with a blood pressure of 112/74 mmHg and a pulse rate of 101 bpm. Her chest was clear with normal first and second heart sounds and pansystolic murmur radiating to the carotids.

Her laboratory investigation showed normal cardiac markers, creatinine, electrolyte and lipid profile, and normal liver and thyroid function tests. Her complete blood count showed mild leukocytosis (white blood cell of 13.30 × 10^3/uL), iron-deficiency anemia with a hemoglobin of 11.0 g/dL, and normal platelet count. Her NT-proBNP was mildly elevated (547.2 pg/mL).

Her electrocardiogram showed sinus tachycardia and left ventricular hypertrophy (LVH) with strain pattern [Figure 1]. Her chest X-ray was normal.

Figure 1

Electrocardiogram showing sinus rhythm and left ventricular hypertrophy with a strain pattern

Her echocardiogram showed LVOT obstruction by a long subaortic membrane (12 mm in length) with severe stenosis and a very high systolic gradient of 123 mmHg, ejection fraction (EF) of 50% with evidence of moderate LVH, right ventricular systolic pressure of 37 mmHg, and mild mitral regurgitation [Figures 2 and 3].

Figure 2

(a and b) Two-dimensional echocardiography parasternal long axis view showing a subaortic membrane (arrow) with turbulence in color Doppler view

Figure 3

Echocardiogram continuous wave Doppler image showing high gradient (132 mmHg) across left ventricular outflow tract cursor

Pelvic ultrasound showed single viable fetus, posterior placenta, and posterior wall uterine fibroid measuring 3 cm × 2 cm. Ultrasound gestational age is 16 weeks, no gross fetal anomalies for gestational age.

The patient was discussed in a multidisciplinary team including cardiologists, cardiothoracic surgeons, and obstetricians, and the consensus was that the patient had severe SAS with very high peak gradient value and so the patient's risk of complication with continuing pregnancy was very high. Repeated echo showed a peak gradient of 135 mmHg in LVOT with a pulse rate of 85 bpm.

The patient was offered subaortic membrane surgical resection. If the fetus had an adverse event during surgery, then termination of pregnancy will be offered in the same setting. The patient preferred to undergo termination and to postpone the cardiac surgery later. However, she was informed that there was a small chance of cardiac complications such as heart failure during termination, and she might require emergency cardiac surgery. The patient eventually preferred to travel to her country to have her cardiac surgery under family support. Unfortunately, she has no further follow-up with us and no available information about her outcome.

DISCUSSION

The course of SAS is often progressive. Unrepaired severe stenosis can proceed to progressive aortic valve damage with aortic regurgitation (AR), left ventricular dysfunction, infective endocarditis, and sudden cardiac death. The predominant feature can be obstruction or AR (seen in >50% of patients). Predictors of progressive disease include peak gradient >30 mmHg, adjacent membrane to the aortic valve, or extension to the mitral valve. Once the peak gradient exceeds 50 mmHg, the risk for significant AR increases.[4]

The 2008 American Heart Association guidelines in congenital heart diseases recommend surgical intervention for SAS when peak gradient >50 mmHg or mean gradient >30 mmHg. Patients with lesser degrees of obstruction can be considered for surgery when there is LV systolic dysfunction (EF <50%), significant AR, marked LVH, or when the patient wishes to become pregnant or to participate in strenuous/competitive sports. Annual follow-up and stress testing are recommended when mean gradient <30 mmHg with no evidence of LVH.[4]

Theoretically, all SAS female patients are at risk of worsening symptoms and hemodynamics during pregnancy. The interaction of SAS with pregnancy is not well explored in dedicated studies, and most of the available data are extrapolated from studies looked primarily for valvular AS.[56]

Old studies suggested a high mortality rate in both maternal (17.4%) and perinatal (31.6%).[7] On the other hand, two recent prospective studies (from ROPAC and Dutch CONCOR registries) showed that AS, including those with severe AS, is quite tolerated during pregnancy in the current era. The mortality rate appears to be close to zero, whereas there is a significantly higher rate of preterm birth and low birth weight, the peak aortic gradient identified as an independent predictor of maternal outcome.[56] Moreover, these patients remain at high risk for cardiac complications during pregnancy, with decompensated heart failure rates ranging from 11.5% to 26.3% and overall increased hospitalizations for cardiac reasons (20.8%).[5]

Pregnancy risk in AS was explored in ROPAC registry; a total of 96 women with moderate or severe AS were identified (out of 2966 pregnancies with cardiac diseases from 99 centers in 40 countries), and more than one-third of cases were severe AS. Severe AS was defined as a peak transaortic gradient more than 64 mmHg (velocity >4 m/s), whereas moderate AS was defined as a peak transaortic gradient more than 36 mmHg. SAS was quite prevalent affecting 22/96 (22.9%) patients and represented one-third of the severe AS cases. Bicuspid aortic valve was the most prevalent etiology for AS 46/96 (53.5%), and rheumatic aortic valve disease was the cause of AS in 18 patients.[5] Data from Dutch CONCOR registry showed a similar prevalence of SAS 14/53 (26%) representing 41% of severe AS cases.[6]

In this review, we summarized all traceable SAS/pregnancy interactions accessible in the literature in the form of case reports. Interestingly, several lessons and future recommendations are shown in Table 1. Most of those cases presented in the third trimester. Our case was the only one to present earlier. One patient had a high peak gradient during pregnancy that decreased on follow-up postdelivery and thus raised a question about the timing of surgery in pregnant women and the cutoff limit gradient to be considered.[1] Another case showed that tiny subaortic membrane can be missed by transthoracic echocardiogram and it should be explored carefully.[8] In labor it is advised to avoid unnecessary supine position in SAS patients as can lead to supine hypotensive syndrome and hemodynamic instability.[9]

Table 1

Summarizing the case reports of subaortic membrane in literature.

Congenital defects	Echocardiographic findings	Age (years)	Symptoms	Pregnancy details	Management	Mode of delivery	outcome	Lessons and recommendations
A subaortic membrane Shapero KS (1)	No LV hypertrophy and peak gradient of 50 mmHg.	39	Asymptomatic, admitted for induction of labor, discovered a murmur which was missed during antenatal care.	Gravida 2 Para 1+1 third trimester, 37 weeks	Conservative	Cesarean section after a trial of induced labor	Good Gradient has improved post-delivery from 50 to 30 mmHg	As LVOT gradient is increased in pregnancy, so they questioned whether guidelines may require reconsideration during pregnancy.
Subvalvular aortic stenosis with grade II mitral valve regurgitation has 2 labors 7 years apart Hyuga S [3]	Mild LV hypertrophy with 55mmHg gradient, raised to 90mmHg in second labor.	28 at 1st labor, 35 at 2nd labor	Blood pressure instability	38 weeks	Patient refused SAS repair after first delivery and declined termination in the second.	Assisted induced delivery done twice in both labors.	Good	Continuous spinal fentanyl infusion combined with minimal bupivacaine doses provided stable hemodynamics and satisfactory analgesia in SAS case.
A subaortic membrane tiny membrane in the LVOT, there was history of heart murmur detected during childhood Dostálová G [8]	LVOT gradient >80 mm Hg.	31	Dyspnea, presyncope.	Not documented but seems 3rd trimester as she experienced presyncope and heart failure in the 8th month.	Her symptoms progressed 6 months after delivery Then abnormal membrane in the LVOT was resected.	Not reported	Good	Tiny subaortic membrane can be overlooked by transthoracic echo and may need transesophageal echocardiography.
Subvalvular aortic stenosis Chen S [9]	Not documented	35	Hypotension and marked bradycardia in supine hypotensive syndrome leading to cardiac arrest during elective cesarean section	Gravida 3, para 1, third trimester, 36 weeks	After hypotension the doctors sped the surgery, newborn delivered, and mother recovered.	Cesarean section	Good for mother and baby after the event.	Supine position in aortocaval compression can cause serious complications in SAS pregnant women.
severe subaortic stenosis by a membrane, cleft mitral valve with severe MR, incomplete atrioventricular canal Guglin M [10]		19	threatened miscarriage	G1 third trimester	Initially, managed conservatively later, underwent surgical repair of all her defects	Cesarean section	Good	summary of recommendations for the management of SAS.
Recurrent subaortic membrane status post–Ross-Kono procedure for LVOT obstruction. Had spontaneous closure of the ventricular septal defect Ali U [11]	Gradient was 50 mg at age of 4, underwent surgery, the SAS recurred at age of 16 with Repeated gradient was 100 mg	27	Presented in 35 weeks gestation in labor.	Gravida 2 para 1, 35+3 weeks	During pregnancy managed conservatively.	induction of labor	mother and infant were doing well in 2 month post-delivery following the Ross procedure,
Our case Long subaortic membrane (12mm) causing obstruction. her 2nd pregnancy was terminated by Cesarian section before expected date	LVOT obstruction with a very high systolic gradient of 132 mmHg, reduced ejection fraction of 50% with evidence of moderate LV hypertrophy.	35	exertional dyspnea, effort intolerance	Gravida 4, para 1+2 abortions, 16 weeks	Offered surgical intervention during pregnancy. But she declined it.	unknown	unknown	-Symptoms may present earlier (2nd trimester in cases with high LVOT gradient. -More data needed on SAS/pregnancy interaction

As LVOT gradient may increase significantly during labor, leading to hemodynamic complication, prompt pain control is advised. Few reports had suggested visits to a high-risk obstetric anesthetic clinic and different anesthetic approaches for AS during labor and delivery.[312]

Chang et al. published a retrospective study including 34 asymptomatic pregnant women to examine changes in Doppler gradients and LV hemodynamics in women with mild-to-moderate valvular and subvalvular AS, in comparison to normal controls. The authors showed an overall increase of peak gradient across the LVOT and aorta (by ~25%, from a mean of 21 mmHg to 27 mmHg) with a decrease of LV systolic function in mild-to-moderate AS. They also reported an increased rate of pregnancy induced hypertension, miscarriage, and preterm delivery with three fetal events reported.[13]

Our patient was gravida 4 and had one child post previous successful delivery and two miscarriages. Unfortunately, we do not have a baseline gradient before pregnancy. On echocardiography, our patient had one of the highest peak LVOT gradients exceeding 132 mmHg and that probably can explain her significant heart failure symptoms early in the second trimester compared to most of the reported cases which tend to present in the third trimester. She had prominent LVH denoting chronicity.

Management through labor, delivery, and the postpartum period requires a multidisciplinary approach to determine the need for surgery and close cardiac follow-up postpartum.[2]

CONCLUSION

Although not clearly highlighted in the literature, SAS represents almost one-fourth of AS cases that complicates pregnancy (from prospective data) and even a higher percentage (32%–41%) of severe AS cases, thus it needs to be evaluated in dedicated studies. Close monitoring is advised in pregnant women with AS for heart failure symptoms and peak aortic gradients, especially in severe AS cases as symptoms may present earlier. A multidisciplinary approach is needed in AS patients during pregnancy with special care for anesthesia in labor targeting prompt pain control and close hemodynamic monitoring.

Consent

As the patient traveled so, a waiver of consent was considered.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.