Peripartum cardiomyopathy (PPCM) is a rare but devastating form of heart failure affecting the parturient during late pregnancy or immediately after delivery. This unique disorder not just endangers the life of mother and progeny but is also a financial burden to the health system due to its potential to cause prolonged and persistent cardiac function insufficiency in the mother.
The diagnostic criteria for PPCM are as follows (Pearson & associates, 2000):
1. Development of heart failure in the last month of pregnancy or up to 5 months             postpartum.
2. Absence of an identifiable cause for cardiac failure.
3. Absence of recognizable heart disease before the last month of pregnancy.
4. Left ventricular dysfunction demonstrated by echocardiography criteria.
Echocardiographic criteria for the diagnosis of PPCM (Hibbard et al., 1999) are the following:
1. Ejection fraction less than 45% or M – mode fractional shortening less than 30% or        both.
2. End diastolic dimension more than 2.7 cm/m2.
Epidemiology:
Although the earlier reported incidence was 1 in every 3000 – 15000 live births in USA, more recent reported incidence is about 1 in 1485 – 4000 pregnancies, thus indicating an increasing trend. Geographical variations exist with higher incidence reported in Africa. Actual incidence of PPCM has not been clearly evaluated in the Indian subcontinent. Pandit et al report is as 1 in 1374 live births from a tertiary referral hospital from South India13.
Many risk factors have been implicated in the development of the disease. These include advanced maternal age, multiparity, Afro-American race, twin pregnancy, preeclampsia, gestational hypertension and diabetes. Uses of tocolytics, high sodium salt, deficiency of certain micro nutrients and smoking during pregnancy have also been implicated. PPCM has a quoted mortality rate of around 20% to 50% indicating the significance of early diagnosis.  
Pathophysiology:
Several mechanisms have been postulated to explain the pathogenesis of PPCM although no single factor has ever been implicated in all the cases. The disease is now known to have a multifactorial pathogenesis. Myocarditis has been shown to be associated with PPCM although the incidence spans a wide range (8.8–78%) in different studies. The  endomyocardial biopsy taken from PPCM  patients have revealed detection of viral genomes like  parvovirus B19, human herpes virus 6, Epstein-Barr virus and human cytomegalovirus by polymerase chain reaction. It has been postulated that changes in immune function during pregnancy may have exacerbated de novo infection or reactivated latent virus in the pregnant females leading to viral myocarditis followed by cardiomyopathy.
Activation of autoimmune response has been cited as another causative factor with compelling evidence supporting it. Sera from PPCM patients contain high titers of autoantibodies against normal human cardiac tissue proteins. In addition, the peripheral blood from PPCM patients demonstrate an abnormal cytokine profile, decreased levels of regulatory T cells and a significant reduction in the plasma levels of progesterone, estradiol and relaxin when compared with other normal pregnant non-PPCM patients. Other probable mechanisms proposed are an accelerated myocyte death (apoptosis), increase in proinflammatory cytokines, excessive prolactin production and coronary microangiopathy. A few reports of familial association of the disease have also appeared which may warrant further evaluation for a probable genetic cause of the disease.
Clinical Features and Diagnosis:
The majority of PPCM patients is 20 to 35 years old and usually present in 2nd or 3rd postpartum month with no known previous cardiac disease. But it may present any time after 36 weeks and may develop up to 5 months postpartum. It may recur in subsequent pregnancies; therefore a cardiology assessment should be performed prior to further conception. Symptoms include weakness, shortness of breath, orthopnoea, cough, PND and palpitations. Other additional features such as abdominal discomfort, dizziness, precordial pain and postural hypotension may also be seen. These patients may have clinical signs such as pedal edema, bilateral basal crepitations, raised JVP, hepatomegaly and gallop rhythm. The onset is usually insidious.
PPCM is a diagnosis of exclusion after ruling out other common causes of cardiac failure such as severe anaemia, thyrotoxicosis, congenital, valvular and ischaemic heart diseases. If a patient presents with persistent or worsening cardiac failure after 36 weeks and up to 5 months postpartum, PPCM should be considered for diagnosis.
The routine investigations recommended are blood, chest x-ray, ECG, and echocardiography. The blood investigations are needed to rule out anaemia, electrolyte dysfunction, kidney, liver, and thyroid abnormality. Chest x-ray may reveal features of failure such as cardiomegaly, pulmonary congestion, and pleural effusion. As chest x-ray features are non-specific, routine use of x-ray should be discouraged during pregnancy. ECG changes may include sinus tachycardia, ST-T segment changes, low voltage complexes, conduction defects, left axis deviation and ventricular hypertrophy and other arrhythmias such as supra ventricular, ventricular extra systoles and ventricular tachycardia may occur. Duran et al identified QRS time of equal to or more than 120ms in the ECG of patients with PPCM as predictor of mortality, indicating a potential impact of QRS time on mortality in PPCM patients14.
Echocardiography is the gold standard investigation and should be done for all patients with suspected PPCM. Typical findings in echo includes dilated left ventricles, increase in end-diastolic left ventricular diameter, ejection fraction of less than 45%, valvular regurgitant lesions, regional wall motion abnormalities and to rule out presence of intra cardiac thrombi. A left ventricular end diastolic diameter of more than 55 mm or an ejection fraction of less than 27% in echo predicts poor long term prognosis in these patients.
Cardiac magnetic resonance imaging provides more accurate measurement of cardiac functions and dimensions and can also be used to guide the site of myocardial biopsy if required. Delayed gadolinium enhancement (DGE) can help to detect inflammatory myocarditis and should be used in patients who do not respond to standard heart failure management. The detection of DGE in order to detect myocardial fibrosis has been indicated as a good prognostic factor. The routine use of endomyocardial biopsy is controversial and may be considered if patient does not respond to two weeks of conventional medicated management. Estimation of C- reactive protein (CRP), interleukin-6, tumour necrosis factor-α, Fas-Apo-1, interferon-γ, N-Terminal-pro Brain natriuretic peptide (NT-proBNP, a serum marker of heart failure), and serum prolactin should now be strongly considered in light of current evidence of inflammatory and autoimmune nature of PPCM.
Medical management:
Systolic dysfunction is the major pathological component of PPCM; medical therapy is as for chronic heart failure. A pre-operative history of heart failure is an important risk factor for postoperative cardiac complications and risk increases when clinical signs are present before surgery. Optimal management of this heart failure should occur before surgery. The goals of medical management in a PPCM patient are to improve oxygenation and maintain cardiac output so as to improve both maternal and fetal outcome. Salt intake should be restricted.
The options of medical therapy include angiotensin converting enzymes inhibitors (ACEIs), angiotensin-2 inhibitors and diuretics. Other therapies include beta-blocker, spironolactone, digoxin, biventricular pacing and anti-coagulants. ACEIs improve survival in all grades of left ventricular failure with angiotensin 2 inhibitors indicated in those who do not tolerate ACEIs. The use of beta blockers in the treatment of chronic heart failure has been shown to improve mortality. Spironolactone has been shown to decrease mortality by 30% in those with severe (NYHA CLASS 3 or 4) chronic heart failure and is useful in relieving symptoms. The use of hydralazine for BP control appears to be relatively safe, although few cases of fetal thrombocytopenia are reported. In addition to medication, some patients gain benefit from biventricular pacing. These patients lack coordination of ventricular contraction, due to delayed pathways of conduction through damaged myocardium. Re-synchronization of left and right ventricular contraction by coordinated stimulation from leads in both ventricles is supported by recommendation from NICE (may 2007).
As in other forms of heart failure, PPCM can lead to both thrombotic and thrombo embolic complication; therefore anticoagulation should be considered. In patients showing clinical evidence of deep vein thrombosis postpartum, warfarin therapy may be initiated. The need for long term warfarin therapy should then be reassessed depending up on the state of LV recovery. Warfarin is teratogenic in early pregnancy and cause fetal warfarin syndrome, while intake in second and third trimester may lead to fetal cerebral haemorrhage, microcephaly, blindness, deafness and growth retardation. Unfractionated heparin on the other hand has low bioavailability in pregnant patients and is associated with thrombocytopenia. Thus, low molecular weight heparins are preferred in pregnancy as they do not cross the placenta, have a lower risk of osteoporosis and thrombocytopenia and their bioavailability is more predictable.
Perioperative management: 
Patients with prenatal diagnosis of PPCM need to be treated by a multidisciplinary approach including obstetrician, anaesthetist, cardiologist, intensivist and neonatologist. The decision to continue pregnancy till term and the mode of delivery should be decided by the team after periodic review. In general, unless there is deterioration in the maternal or fetal well being, there is no need for emergency delivery and the pregnancy may be allowed to continue till term.           The overall aims of anaesthesia are to
1. Avoid tachycardia
2. Avoid/minimize the effects of negative inotropic agents.
3. Prevent increase in afterload.
4. Maintain adequate preload in the presence of elevated LVEDP

Induction of labour should be considered if patient medical condition worsens. The vaginal delivery needs to be done with continuous hemodynamic monitoring and even invasive monitoring has been advocated according to patient’s profile. Labour analgesia should be offered for these patients because of its ability to reduce sympathetic stress response of labour pain. The second stage of labour needs to be curtailed by application of forceps or vacuum. Caesarean section should be reserved for obstetric indications but should be considered in a rapidly decompensating patient where medical therapy fails. The various options for labour analgesia are Graded Epidural, combined spinal epidural (CSE) and continuous spinal analgesia (CSA). Fluid should be administered with great care during this period as these patients can easily go for volume overload. Auto transfusion after delivery has to be countered by the use of vasodilators.
Caesarean delivery avoids the increase in stroke volume and cardiac output that uterine contractions produce and may be preferred by some obstetricians. Caesarean section in PPCM patients have been performed under general as well as regional anaesthesia. The advantage of regional anaesthesia in PPCM patients are because of sympatholysis induced reduction of preload and afterload. However, single shot spinal anaesthesia is not recommended due to uncontrolled sympathetic blockade and hemodynamic instability.
Epidural anaesthesia with a gradual titrated dose of local anaesthetics offers better hemodynamic control in these high risk patients. The presence of an epidural catheter will help to provide better postoperative analgesia. The major disadvantages of this technique are failure or partial anaesthesia which may lead to forced conversion to General Anaesthesia. Combined Spinal Epidural (CSE) has also been successfully used in PPCM patients. The advantages of CSE include lower rate of failure, smaller drug requirement, easy titrability with fewer hypotensive episodes (as it can be precisely titrated), faster onset with excellent analgesia, better patient satisfaction and postoperative pain score. But it has disadvantages like technical difficulty and post dural puncture headache. PDPH incidence may be reduced by the use of 27G pencil point needle.
Some anesthesiologists have successfully used Continuous spinal anaesthesia (CSA) for caesarean section in patients with severe PPCM. CSA has theoretical advantage over CSE in terms of rapid onset with precise titrability requiring less local anaesthesia, but it can be associated with higher incidence of PDPH and neurological complications. Avoidance of microcatheter and lignocaine has resulted in reduction of these complications. Local anaesthetic infiltration along with ultrasound guided bilateral TAP block or bilateral ilioinguinal nerve block can be used in extreme cases. Although it has got minimal hemodynamic effects, higher incidence of failure is a major obstacle for this technique.
Regional anaesthesia offers the advantage of avoiding cardio depressant anaesthetic drugs, reduced venous stasis and thereby significantly reduced incidence of thromboembolism.                    Regional Anaesthesia is contraindicated in patient on warfarin or if has received LMW Heparin in the last 12 hrs. Regional Anaesthesia is also not preferred in an emergency caesarean section and severely dyspnoeic patients. General Anaesthesia (GA) may have to be used in these patients. Though GA has the advantage of controlling airway and ventilation, hemodynamic stress from rapid sequence induction can be dangerous more so if opioids are not used. Both inhalational and intravenous techniques have been used but both may lead to severe materno - fetal cardio respiratory adverse effects. General Anaesthesia already adds to the existing risk of thromboembolism.
Although caesarean section have been successfully conducted in PPCM patients with routine noninvasive monitors, invasive parameters like IBP, CVP or PCWP and trans esophageal echocardiography are recommended for monitoring during anaesthesia. They are ideally initiated initiated before anaesthesia is started. The benefits of invasive and advanced monitoring may outweigh all arguments against it in severe cases. Ergometrine should preferably be avoided and oxytocin should be given as an infusion or slowly titrated to response.
Postoperatively, these patients are routinely monitored in an ICU as they may require ventilator, inotropic support and invasive monitoring. Parentral opioids or epidural catheter should be used for post-operative analgesia. Anticoagulant should be started early in view of risk of thromboembolism. All preoperative cardiac medications should be continued.
Prognosis:
Prognosis of PPCM patient is related to presentation as well as to recovery of ventricular dysfunction. About 60 – 90 % of patients have complete recovery. Full recovery is documented by attainment of NYHA class 1 and LVEF of more than 50%. The patients having baseline LVEF of less than 25% have worst prognosis and may require heart transplantation. Basal level of NT – ProBNP and IFN-γ are good prognostic markers. Women who recover from PPCM are at high risk of recurrence in subsequent pregnancies. The risk of recurrence is approximately 21% in women in whom the left ventricular function returns to normal and 44% in those who have persistent left ventricular dysfunction. Women with persistent left ventricular dysfunction should be advised to avoid pregnancy.
Conclusion:
PPCM is a disease associated with high morbidity and mortality. PPCM requires a multi-disciplinary approach with early diagnosis, preoperative optimization, careful monitoring, appropriate anaesthetic technique and vigilant postoperative care. Regional anaesthesia offers advantages like preload and afterload reduction, reduced incidence of thromboembolism and is generally preferred in PPCM patients. General anaesthesia has disadvantages like myocardial depression and hemodynamic instability and may be fatal. GA may be used only when regional anaesthesia is contraindicated or in emergency scenarios.
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