Cardiomyopathy encompasses a wide spectrum of heart muscle disease, which can have an impact on the patient’s ability to sustain the increased cardiac workload of pregnancy. Pregnancy can also unmask previously unknown cardiomyopathy. The outcome for both mother and baby is often related to the patient’s functional class prior to pregnancy, and a multidisciplinary approach to managing this challenging group of patients is pivotal.
Introduction
Cardiomyopathy is a disease of the heart muscle, which can be inherited or acquired and sometimes affect the performance of the heart muscle. All cardiomyopathies alter the shape and size of the heart. This can have an impact on its ability to sustain the increased workload required during pregnancy. During pregnancy, the cardiac output increases by about 30–50%, and this may cause decompensation in patients who have heart muscle disease. Similarly, the increased cardiac workload in pregnancy can unmask previously undiagnosed cardiomyopathy.
The common final pathway/natural history of all cardiomyopathies is heart failure. In predominantly left ventricular failure, patients suffer from pulmonary congestion and pulmonary oedema; in mainly right-sided failure, they develop peripheral oedema and/or ascites and pleural and pericardial effusions. Most patients who have end-stage heart failure will have findings of both right and left heart failure, but they are less likely to be found in the antenatal clinic.
Genetic inheritance patterns
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Autosomal dominant: a 50% chance of offspring being affected, with the same risk for male and female offspring
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Autosomal recessive: a 25% chance of offspring being affected, same risk for male and female offspring
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X-linked dominant: the dominant gene is on the X-chromosome; male and female offspring are affected, males often more severely as they only have one X-chromosome. All daughters will be affected if the father is affected, all sons will be unaffected. If the mother is affected, 50% of daughters and 50% of sons will be affected.
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X-linked recessive: the recessive gene is on the X-chromosome; male offspring are affected as they only have one X-chromosome. All daughters are carriers, unless they are homozygous (mother and father carry the gene). If the father is affected, only the daughters will be carriers. All sons are unaffected. If the mother is a carrier, 50% of her daughters will be carriers and 50% of her sons will be affected.
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Mitochondrial inheritance: also known as maternal inheritance. Mitochondria are inherited from the mother; therefore, male and female offspring may be affected, but only female patients can pass on the faulty mitochondria to their offspring.
Genetic inheritance patterns
- •
Autosomal dominant: a 50% chance of offspring being affected, with the same risk for male and female offspring
- •
Autosomal recessive: a 25% chance of offspring being affected, same risk for male and female offspring
- •
X-linked dominant: the dominant gene is on the X-chromosome; male and female offspring are affected, males often more severely as they only have one X-chromosome. All daughters will be affected if the father is affected, all sons will be unaffected. If the mother is affected, 50% of daughters and 50% of sons will be affected.
- •
X-linked recessive: the recessive gene is on the X-chromosome; male offspring are affected as they only have one X-chromosome. All daughters are carriers, unless they are homozygous (mother and father carry the gene). If the father is affected, only the daughters will be carriers. All sons are unaffected. If the mother is a carrier, 50% of her daughters will be carriers and 50% of her sons will be affected.
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Mitochondrial inheritance: also known as maternal inheritance. Mitochondria are inherited from the mother; therefore, male and female offspring may be affected, but only female patients can pass on the faulty mitochondria to their offspring.
Implantable cardioverter defibrillators
Patients with cardiomyopathy sometimes have implantable cardioverter defibrillators (ICDs) for primary or secondary prevention of life-threatening arrhythmias. Maternal and neonatal outcome is mostly good, although complications can occur from not only the device itself (lead displacement or breakage, thrombus on leads, infection, etc.) but also the underlying medical condition . In women with ICDs, the device must be switched off for any surgical intervention where diathermy is used, as the electrical interference may be misinterpreted by the device as ventricular fibrillation and inappropriate shocks delivered. Input from a pacing technician is advisable.
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the most common type of inherited cardiomyopathy with a prevalence of 1 in 500 . It is inherited in approximately 90% of cases, and the inheritance pattern is mostly autosomal dominant, that is, 50% of offspring will inherit the condition . Penetrance is incomplete, but increases with age .
Histologically, this disease is characterised by myocyte disarray and replacement fibrosis, the degree of which can be very variable – some patients have no myocardial fibrosis, some have a very high scar burden. Research has shown that the amount of scar is proportional to not only adverse outcome, mainly the development of heart failure, but also arrhythmia .
Patients with HCM have abnormal thickening of the heart muscle, typically the septum, but other parts of the left ventricle (LV) and sometimes also the right ventricle (RV) may be affected. The increased muscle mass renders the heart muscle stiff and non-compliant, therefore LV filling pressures are high. This is transmitted to the left atrium, which typically enlarges due to elevated pressures. LV hypertrophy (LVH) develops at the expense of cavity size. Therefore, patients with HCM tend to have smaller stroke volumes. In some cases, the thickened septum causes a dynamic obstruction to the left ventricular outflow tract (LVOT), with a pathophysiology similar to aortic stenosis. Some patients only have LVOT obstruction during exercise, but for many, there is obstruction at rest. During pregnancy, when cardiac output needs to rise by 30–50%, patients are unable to sufficiently increase their stroke volume as a result of outflow obstruction in conjunction with the small stroke volume due to a small LV cavity size. The pregnancy-associated fall in systemic vascular resistance increases the pressure gradient across the LVOT further ( Fig. 1 ).
HCM: symptoms
Many patients with HCM are asymptomatic. Symptomatic patients typically present with breathlessness due to outflow tract obstruction, diastolic disease, palpitations or syncope from atrial or ventricular arrhythmias, or sudden death as a result of sustained ventricular arrhythmia.
If outflow tract obstruction is present, stroke volume cannot increase adequately during pregnancy and/or on exercise and hence the main symptom is breathlessness. In severe cases, where the obstruction is severe, patients may present with syncope. Syncope can, however, also be a symptom of arrhythmia, and patients with LV wall thickness of >30 mm are particularly at risk from arrhythmia and sudden death.
HCM: investigations
Twelve-lead ECG: This is likely to show LVH by voltage criteria and typically ST-segment or T-wave changes, depending on the distribution of myocardial hypertrophy. An apical dominant HCM will show deep T-wave inversion in V1–V3 or V4; other phenotypes may show ST depression in the lateral chest leads relating to hypertrophy and strain.
Twenty-four-hour ECG: Patients with HCM may have atrial and/or ventricular arrhythmias. The latter is associated with sudden death. Arrhythmia may be asymptomatic; therefore, a 24-h ECG should be arranged even in the absence of symptoms.
Echocardiography is used to characterise the degree and distribution of hypertrophy and degree of potential LVOT obstruction.
Cardiovascular magnetic resonance (CMR): This is rarely required in pregnancy and contraindicated in the first trimester of pregnancy. Outside pregnancy, it is frequently used to better characterise ventricular and outflow tract anatomy, and when given in conjunction with gadolinium contrast, can assess myocardial scar burden.
HCM: preconception counselling
Genetic counselling should be offered and the patient made aware that the chances of passing on the condition to their offspring are 50%.
It is important to establish a pre-pregnancy functional status and to assess risk in every patient who wishes to embark on pregnancy. New York Heart Association (NYHA) functional class and whether there is a history of cardiac events, including arrhythmia, syncope, or significant breathlessness, should be determined, because symptoms present in the non-pregnant state are likely to be exacerbated by pregnancy .
HCM: management during pregnancy and post partum
Patients with HCM are at risk from atrial and ventricular arrhythmia, pulmonary congestion, that is, pulmonary oedema, and increasing outflow tract obstruction. In most cases, however, pregnancy is well tolerated, especially in previously asymptomatic patients. Adverse outcomes are more common in patients with poor pre-pregnancy functional class and those with an adverse risk profile . Patients with previous arrhythmic events are more likely to suffer recurrences during pregnancy. Atrial arrhythmia, especially atrial fibrillation (AF) from left atrial dilatation, is common in patients with HCM. Because the LV is non-compliant and requires high filling pressures, the atrial contribution to ventricular filling, which is normally between 10% and 30%, is very important and in patients with HCM can contribute up to 50% of LV filling. When AF occurs, patients immediately lose approximately half their stroke volume, which is poorly tolerated, particularly when the heart rate is high and there is little time for passive LV filling, further reducing cardiac output. Prompt restoration of sinus rhythm (either by drug treatment or direct current (DC) cardioversion) is essential; however, if this cannot be achieved, rate control is paramount to allow time for LV filling. Low-colloid oncotic pressures during pregnancy, in combination with high left atrial pressures, which rise further if AF develops, contribute to an increased risk of pulmonary oedema . AF increases the risk of thromboembolism and thromboprophylaxis should be considered. Although maternal mortality is increased when compared with the normal population, the outcome is mostly good, and the small number of maternal deaths in this patient group occurred in women with particularly high risk . Infant outcome is closely related to the mother’s functional class and adversely affected by the presence of maternal left heart obstruction .
In most patients, vaginal delivery is appropriate with careful peri-partum monitoring of fluid balance and cardiac rhythm.
Dilated cardiomyopathy
This type of cardiomyopathy is characterised by left ventricular dilatation combined with impairment of systolic function. The RV may be affected, but not always. Dilated cardiomyopathy (DCM) can be divided into idiopathic (or primary) and acquired (or secondary) forms. Myocarditis, alcohol or other toxins, endocrine and autoimmune disorders and nutritional factors can all cause DCM, and this list is not exhaustive. In idiopathic DCM, the aetiology often remains unknown. The idiopathic form of DCM is familial in approximately a third of patients . Most familial cases have an autosomal dominant inheritance pattern; some are autosomal recessive, with mutations in sarcomeric or cytoskeletal proteins and a number of others. X-linked forms exist, for example, DCM associated with Duchenne or Becker muscular dystrophies, or on its own in X-linked DCM. Mitochondrial cytopathies have also been implicated.
In DCM, regardless of the aetiology, there is dilatation of the LV cavity with reduced wall thickness, but increased LV mass, and usually impaired LV systolic function. Often, there is dilatation of all cardiac chambers, and RV dysfunction may be present. Atrial dilatation and slow-flowing blood encourage formation of thrombi, predisposing to thromboembolic complications ( Fig. 2 ).
DCM: symptoms
The most common symptoms of dilated cardiomyopathy are breathlessness, fatigue, exercise intolerance and fluid retention. The severity of symptoms is at least in part related to the degree of LV impairment – some patients with mildly impaired ventricles may be entirely asymptomatic, and their disease may only be unmasked by the added haemodynamic burden of pregnancy. Palpitations in DCM may be a symptom of atrial and/or ventricular arrhythmia. Certain forms of inherited DCM (mutations in the lamin A/C gene) are associated with conduction disease and symptomatic bradycardia – the patient may present with syncope, or simply breathlessness and effort intolerance. Those DCM patients with shortness of breath at rest are likely to have poorer LV function and are at risk of developing overt heart failure with pulmonary oedema during early pregnancy.
DCM: investigations
A 12-lead ECG may be normal, but may show AF (in which case anticoagulation should be initiated). There may be left bundle branch block or other conduction disease.
Twenty-four-hour ECG monitoring may show paroxysmal AF and other atrial or ventricular rhythm disturbances even in the absence of symptoms, and therefore should be performed in every patient with DCM.
Echocardiography is the mainstay of assessing LV function during pregnancy.
DCM: preconception counselling
Pregnancy in women with DCM is associated with adverse outcome, especially in those with significantly impaired LV function (moderate or severe LV systolic dysfunction, ejection fraction (EF) <45% on echocardiography). In this cohort, adverse events such as heart failure and ventricular tachyarrhythmias occurred in more than a third of pregnancies in one series . This study also reported an adverse effect of pregnancy on the patient’s cardiac function, if only temporarily in most. Deterioration of LV systolic function tends to occur in the later stages of pregnancy with the highest event rate in women in NYHA class III and IV and those with an LV EF <40%. Foetal events such as low birth weight and preterm delivery are more common in patients with DCM.
To better advise the patients about their personal risk, assessment of LV function and exercise tolerance is important as part of their preconception counselling work-up. If the patient is on heart failure medication known to have teratogenic effects such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), they should be stopped prior to conception with surveillance echo put in place to determine if LV function declines as a consequence of their withdrawal. If LV function then deteriorates even before pregnancy, the patient should be advised against pregnancy. Furthermore, severely impaired LV function carries a poor prognosis irrespective of pregnancy and is associated with considerable disability, the impact of which should be considered when looking after a young child.
DCM: management during pregnancy and post partum
Patients with known DCM, who become pregnant, need to stop ACE inhibitors and/or ARBs, but should remain on the beta-blocker throughout pregnancy and the post-partum period. Pregnant patients with DCM are at high risk because LV function can deteriorate. Therefore, they need close monitoring clinically and echocardiographically. If LV function deteriorates significantly and/or the woman develops symptoms of heart failure, she may need to be delivered irrespective of the gestational age of the foetus. In the management of pregnant patients with DCM, diuretics are used to manage fluid status, and nitrates or hydralazine can be used to reduce preload.
Palpitations need to be thoroughly investigated with 24-h ECGs or cardiac loop recorders if less frequent. AF requires therapeutic anticoagulation with low-molecular-weight heparin (LMWH) to prevent thromboembolic complications. Tachyarrhythmias (atrial or ventricular) may be poorly tolerated and needs immediate treatment to restore sinus rhythm to prevent cardiac decompensation.
In dilated ventricles, functional mitral and tricuspid regurgitations are common. The mitral regurgitant volume will further increase left atrial pressures and lower the threshold for developing pulmonary oedema. Careful blood pressure and fluid balance management is essential.
The clinical signs of incipient cardiac failure can be very subtle in a young woman. A new dry cough should be treated with suspicion and deterioration in effort tolerance can reflect the early stage of pulmonary congestion, while pink frothy sputum of overt pulmonary oedema should be considered a peri-arrest situation.
Prior cardiac events or arrhythmia, baseline NYHA >class II and reduced systemic ventricular systolic function (EF < 40%) are relevant predictors of poor maternal outcome for this patient group. Neonatal events are most likely in women with NYHA >class II during the baseline prenatal visit, multiparous status and use of anticoagulants throughout pregnancy .
Peripartum cardiomyopathy
This type of cardiomyopathy is defined as new heart failure in pregnancy with impaired LV systolic function in the absence of any other cause, occurring in the last month of pregnancy until 5 months post partum, although recent publications set the time frame less tightly. Peripartum cardiomyopathy (PPCM) is a diagnosis of exclusion.
In the Western world, PPCM affects 1 in approximately 3000 pregnancies; more commonly in women of African descent and least commonly in women of Hispanic ethnic origin . In some parts of the world, for example, Haiti, the incidence may be as high as 1 in 300 pregnancies .
The aetiology remains unknown, and a number of causative factors have been implicated, which are well summarised in a review article by Sliwa et al. . These include autoimmune inflammation and myocarditis with and without viral triggers, foetal microchimerism, increased cardiomyocyte apoptosis and a familial association between PPCM and DCM.
Several risk factors for PPCM have been suggested, including multiparity, multigravity, older maternal age, pre-eclampsia and prolonged tocolysis, but many of these remain controversial . In a cohort described by Elkayam et al., 40% of women with PPCM were primiparous . A recent meta-analysis of PPCM found no association between pre-eclampsia and PPCM, although new data suggest an imbalance of angiogenic factors in women with PPCM, with similar features to those seen in pre-eclampsia .
The outcome in PPCM is strongly dependent on recovery of LV function. Reported recovery rates vary considerably from 25% to almost 80%, and functional recovery can occur well beyond 12 months post partum.
Similarly, recurrence risk of heart failure in a subsequent pregnancy is associated with lack of LV functional recovery after the index pregnancy. An LV EF ≥ 55% was the most important determinant for freedom from relapse in a post-PPCM pregnancy in a study by Fett et al. .
PPCM: symptoms
The onset of symptomatic heart failure in PPCM may be insidious, much like the symptoms of DCM; however, there may be rapid progression. Reduced effort tolerance, swelling of hands and feet or new abdominal distension and inability to lie flat may signal early decompensation. The full-blown picture of acute heart failure with low cardiac output, pulmonary oedema and tissue hypoxia is a life-threatening emergency. Incipient heart failure may mimic symptoms of pulmonary embolism or respiratory tract infection.
PPCM: investigations
See ‘DCM: Investigations’.
Echocardiography: In PPCM, LV systolic function is impaired on echocardiography; however, unlike DCM, the ventricular cavity may be normal in size.
Exercise stress echocardiography: After the index pregnancy, stress echo can be used to assess contractile functional reserve. This can aid risk stratification for a subsequent pregnancy (see under ‘PPCM preconception counselling’).
Chest X-ray: This may be useful to differentiate between pneumonia, pulmonary embolism and pulmonary oedema.
PPCM: preconception counselling
In PPCM this only applies to a subsequent pregnancy. Many clinicians actively discourage patients with PPCM from considering another pregnancy, especially if there is residual impairment of LV function. If however, despite the risks, a future pregnancy is planned, it is useful to trial a period of ACE inhibitors with monitoring of LV function by echo to establish whether discontinuation of the ACE inhibitor alone will result in deterioration of LV function. If this is the case, pregnancy is inadvisable as LV function is likely to deteriorate further in pregnancy, risking life. Exercise stress echocardiography can determine contractile reserve prior to embarking on a further pregnancy: Those with good contractile reserve will have the lowest-recurrence risk.
PPCM: management during pregnancy and post partum
The management of PPCM is the same as for any other type of acute heart failure, focussing on reducing preload with diuretics and venous pooling agents such as nitrates or hydralazine, managing fluid status and symptoms with diuretics and treating and preventing arrhythmia using beta-blockers. Digitalis can augment systolic function and is safe to use. Anticoagulation for prevention of thromboembolic complications may be added and continued post partum if the LV EF remains ≤30%. ACE inhibitors should be started as soon as possible after delivery and they are safe for breastfeeding.
Pre-term delivery may become necessary if rapid deterioration of LV function occurs.
In a subsequent pregnancy, close monitoring of LV systolic function is mandatory to detect early deterioration, thus avoiding cardiac decompensation. Contraception should be discussed prior to discharge from hospital.
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