Peripartum Cardiomyopathy: A Systematic Review (Classification, Evaluation and Management of Cardiomyopathies) Part 3

Management of peripartum cardiomyopathy

When considering treatment during the peripartum period, a multidisciplinary approach is needed. Involvement of a maternal-fetal medical team, including a cardiologist, obstetrician, anesthetist, intensivist, and neonatologist is imperative as earliest as possible after the diagnosis. The type of monitoring and care should be individualized to minimize maternal and fetal morbidity and mortality.

General management of peripartum cardiomyopathy

The medical treatment is generally similar to that for other forms of non-ischemic dilated cardiomyopathy, with some possible exceptions because of the risks of certain drugs on the fetus and newborn. The aims of medical treatment should be to reduce cardiac afterload and preload, while increasing myocardial contractility, to prevent complications, particularly thromboembolism, cardiac arrhythmia, progressive heart failure, and to improve long-term prognosis. Current therapeutic options consist of conventional supportive treatment for acute and chronic heart failure.

Management of acute heart failure

The principles of treatment in PPCM are no different than those applying to acute heart failure from other etiologies (Dickstein et al., 2008). A careful bedside clinical assessment may be helpful to identify the hemodynamic profile. Acute heart failure is usually manifested by worsening pulmonary congestion to pulmonary edema and hypoxemia, peripheral congestion with large weight gain, or low output status indicated by signs of hypoperfusion. All patients should be hospitalized and closely monitored. Oxygen therapy should be promptly administered in order to relieve symptoms, while achieving an arterial oxygen saturation of > 95%. Non-invasive ventilation with a positive end-expiratory pressure of 5-7.5 cm H2O should be used when necessary. Extracorporeal membrane oxygenation to treat severe pulmonary edema shortly after delivery has been reported to be useful (Yang et al., 2007).

Patients with significant volume overload but adequate perfusion are treated with intravenous diuretics, with an initial bolus of furosemide 20-40 mg i.v. Particular potential adverse effects of diuretics were reported during pregnancy, such as pancreatitis, decreased carbohydrate tolerance (Lindheimer & Katz, 1973) bleeding, and hyponatremia in newborns (Ferrero et al., 2003).

Intravenous nitrates may be added when diuretics are inadequate in controlling symptoms. Nitroglycerin starting at 10-20 up to 200 |g/min is safe when systolic blood pressure is > 110 mmHg. Nitroprusside may be used in certain cases, but theoretically, accumulation of its catabolites thiocyanate and cyanide may be harmful to the fetus (Egan et al., 2009). Nesiritide is insufficiently studied in human pregnancy (Cruz et al., 2010). Inotropic agents can be used without unnecessary delay in patients with low output status or those with persistent congestion despite diuretic and/or vasodilatator therapy. Dobutamine or levosimendan are strongly recommended when needed. Small studies with levosimendan suggest persistent hemodynamic improvement attributable to production of an active long half-life metabolite (OR-1896), and no safety concern, but breast-feeding should be avoided (Benezet-Mazuecos & de la Hera, 2008; De Luca, 2006). Mechanical ventricular support and cardiac transplantation are needed in patients dependent on inotropic agents, or intra-aortic balloon pump counterpulsation, despite optimal medical strategy. Surgical support with ventricular assist devices may be considered in appropriately selected patients as a bridge to recovery or to cardiac transplantation. Heart Failure Association of the ESC Working Group on PPCM recommends an individualized discussion between experts in such cases, as the optimal strategy in PPCM is not known (Sliwa et al., 2010a). If the type of ventricular assist devices is discussed, two prosthetic ventricles – BiVADs and CardioWest TAH, depending on body surface area, heart size and presence of multiorgan failure were proposed (Zimmerman et al., 2010). Complications may occur with ventricular assist devices, such as a high incidence of thrombotic events (Potapov et al., 2008). Recovery of myocardial function can occur in approximately 15% of patients with PPCM on ventricular assist device support (Murali et al., 2005). If the clinical improvement does not occur, cardiac transplantation should be considered. Since 1987, when Aravot et al. reported their first experience (Aravot, 1987, as cited in Abboud, 2007), several case series were treated by heart transplantation with mixed results. In 1994, Keogh et al. demonstrated no difference in survival rates for cardiac transplantation in women with dilated cardiomyopathy, irrespective of etiology, but higher rates of early rejection in PPCM were noted (Keogh, 1994, as cited in Zimmerman, 2010). Other authors supported the hypothesis of an overactive immunological response in "myocarditis-like" PPCM, which predisposes to recurrent severe rejection, and subsequent development of fatal transplant-associated complications. A recent prospective study demonstrated that survival and freedom from cardiac allograft vasculopathy in PPCM was similar to that of women with other indications for heart transplantation (Rasmusson et al., 2007). At the present time, based on available data, 0-11% PPCM patients undergo heart transplantation, with a similar outcome compared with other etiologies of heart failure (Sliwa et al., 2010a). Generally, heart transplantation in PPCM is associated with survival rates similar to that in patients with idiopathic dilated cardiomyopathy (88% at 2 years, and 78% at 5 years) (Murali et al., 2005).Very recently, a long term survey on 8 patients with PPCM (mean post-transplant survival 7.1 years) has shown that cardiac transplantation alone can be a successful option (Zimmerman et al., 2010).

Management of stable heart failure

There are no clinical trials to support any particular treatment regimen for PPCM. After delivery, the patient should be treated according to the current guidelines for heart failure (Pearson, 2000; Sliwa, 2010a). During pregnancy and lactation, the management approach must consider the welfare of the fetus along with that of the mother, so several restrictions to these guidelines will be applied.

Dietary restrictions and lifestyle changes are essential and complementary to pharmacological therapy. Fluid restriction to < 2 liters per day and salt restriction (2-4 g per day) are advisable for volume overload control, particularly when NYHA class III and IV symptoms occur. Daily monitoring for edema and weight loss is clinically useful (Oakley et al., 2003). Smoking and alcohol cessation is strongly recommended. Strict bed rest was the standard in the past, still not recommended, except the patients with severe symptoms. Regular modest exercise may be resumed after relief of symptoms (Pyatt &Dubey, 2011; Sliwa 2006a). Since many of pharmacological agents are secreted in the breast milk, breast-feeding is not advised in patients with PPCM (Sliwa et al., 2010a).

Diuretics should be used cautiously because of decreasing placental perfusion with aggressive administration (Egan, 2007; Sliwa 2006a). After delivery, diuretics are safe to reduce preload, and relieve symptoms of pulmonary congestion and volume overload (Amos, 2006; Oakley, 2003). Loop diuretics, such as furosemide, are most frequently used and safer during hospitalization. Thiazide diuretics may be added, if loop diuretics are insufficient, or used in mild cases (Oakley, 2003; Sliwa 2010a). Possible increase of risk of births defects or fetal thrombocytopenia, were reported (Cruz et al., 2010). On experimental studies, spironolactone is reported to have antiandrogenic effects during late pregnancy, but it can be safely added in postpartum period (Pyatt &Dubey, 2011). Eplerenone should be also avoided during pregnancy, as its effects on human fetus are insufficiently studied (Muldowney et al., 2009).

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) are contraindicated, because of severe fetal toxicity in the 2nd and 3nd trimester of pregnancy, particularly on kidney, resulting in oligohydramnios, fetal renal failure, and neonatal death, but also hypocalvaria, limb contractions, hypoplastic lungs (Cruz et al., 2010). After delivery, or in postpartum onset PPCM, ACEI and ARB are efficient agents to reduce the afterload, and are strongly recommended, as it has been demonstrated to improve survival in all patients with systolic heart failure. It is also recommended the patient counseling about the teratogenic potential of these drugs, with a recurrent pregnancy (Cruz et al., 2010). Some of ACEI, such as captopril and enalapril, are safe during breast-feeding (Ghuman et al., 2009).

Hydralazine and long-acting nitrates are considered safe and useful to reduce preload. The combination can replace ACEI/ARB during pregnancy, or if there is drug intolerance, and may be added to standard therapy in symptomatic patients (Moioli et al., 2010). The agents are reported to be especially effective and further increase survival among African-American patients with NYAH II and III class heart failure (Hunt et al., 2009). The combination is also compatible with breast-feeding.

pp-blockers have not been tested in PPCM, but have been safely used in pregnancy-induced hypertension. pi-selective blockers are preferred, as p2–blockade is theoretically reported to have anti-tocolytic effect (Ghuman et al., 2009). The benefit of these drugs to maternal survival usually outweighs the potential risk to the fetus and newborn. The risks consist of growth retardation, resulting in low-birth-weight newborns, hypoglicemia and bradycardia. Therefore, care should be given when these drugs are used in late pregnancy. P-blockers are recommended for all patients with PPCM, unless contraindicated, as these drugs improve symptoms, ejection fraction, and long term prognosis, reduce the risk of arrhythmia and sudden death. Because transient worsening of heart failure may appear with initiation of therapy, patients should be stable, with minimal evidence of volume overload, and doses should be titrated cautiously. Although carvedilol has been shown to improve overall survival in dilated cardiomyopathy, no safety information related to its use during pregnancy are available. Therefore, use of metoprolol is preferred under careful monitoring, as the drug is also compatible with breast-feeding (Abboud, 2007; Cruz, 2010). Antiarrhythmic drugs, although well tolerated, should be used only in the acute setting, because their safety for fetus cannot be guaranteed. P-blockers are often adequate for treating supraventricular arrhythmias, also in chronic use. Sotalol or amiodarone may be needed, but, considering their systemic side effects during chronic use, are not recommended. Calcium channel blockers, because of their negative inotrop effects, are also not recommended. Ventricular arrhythmias may be frequently life-threatening, and should be managed aggressively. Class I and class II antiarrhythmic agents are not recommended, because the drugs are poorly tolerated and have proarrhythmic effect. Digoxin is safe during pregnancy, even if it crosses the placental barrier. Careful monitoring of serum levels is recommended, because of the narrow therapeutic-to-toxic window. A digoxinemia of < 11.2 ng/ dl and early use of the drug in symptomatic women with ACEI/ ARB contraindications are recommended (Cruz et al., 2010). Digoxin is also secreted in breast milk, but no adverse effect has been described in newborns (Moioli et al., 2010). In appropriate patients, electrical cardioversion may be necessary, after transesophageal echocardiography rules out the presence of a left atrial thrombus.

Antithrombotic therapy is recommended as pregnancy and puerperium are prothrombotic states. In addition, LV dysfunction (particularly ejection fraction < 35%), severely dilated cavities, and mural thrombus, history of venous thromboembolism and atrial fibrillation are associated with an increased risk of thromboembolic events. A recent study of 182 women with PPCM demonstrated an incidence of 2.2% for thromboembolic complications (Goland et al., 2009). VKA antagonists are contraindicated prior to delivery, because of their risk of fetal and neonatal cerebral hemorrhage, and central nervous system anomalies for warfarin. Heparins are considered necessary and preferred, as they do not cross the placental barrier, and are found in breast milk in significant amount. Low-weight molecular heparins are preferred, as they have a lower risk of premature maternal osteoporosis and thrombocytopenia. Also, low-weight heparins have a short half-life, so they can be discontinued at least 12 hours prior to delivery, to prevent maternal hemorrhage, and resumed 12-24 hours after delivery. Currently, low-weight heparins are safely used in weight-adjusted doses. A strictly adaptation using anti-Xa monitoring is necessary in women at extremes of body weight, or with renal disease. Fondaparinux cannot be used during pregnancy, as there are no consistent data. In 5-7 days postpartum, heparin can be replaced with VKA antagonists, even to breast-feeding mothers (Torbicki et al., 2008). Cardiac resynchronization therapy and implantable cardioverter/defibrillators have individualized indication, otherwise very difficult to decide in the context of the natural history of PPCM and lack of specific data. The main concern is the usefulness of such methods in patients who may not need them, if ventricular function will recover. For this reason, the indication is advisable when LV ejection fraction < 35% persists after 6 months following presentation. Patients with recurrent symptomatic ventricular arrhythmias may be candidates for an implantable defibrillator. If NYHA III and IV heart failure symptoms and a QRS duration > 120 ms are present, cardiac resynchronization may be required (Sliwa et al., 2010a). Novel therapies are emerging, but the available data are inconsistent and limited. Immune modulatory therapy in PPCM is not clear, although an immune pathogenesis has been postulated. The beneficial effects of intravenous immunoglobulin therapy have been inconsistently demonstrated by several studies. Likewise, immunosuppressive drugs, such as azathioprine, cyclosporine or steroids, have shown mixed results. For all these reasons, a multicenter prospective clinical trial in PPCM is needed to support use of such agents. Some studies suggested that immunosuppressive drugs might be helpful in patients with active biopsy proven lymphocytic myocarditis, only after active viral infection is excluded (Sliwa, 2006a; Zimmerman, 2005). Also, recent studies demonstrate the role of cardiotrophic viruses in some cases of idiopathic dilated cardiomyopathy (Kuhl, 2005a, 2005b), but only one study had demonstrated viral genomic material in endomyocardial biopsy from patients with PPCM (Bultmann et al., 2005). At the present time, the role of immunosuppressive therapy in women with negative biopsies remains unknown. It is important to note that current therapies with ACEI, ARB (Godsel et al., 2003), and p blockers (Pauschinger et al., 2005) may have an additional effect on controlling the overactive immune system in PPCM. Also, immunomodulatory therapy acting on inflammatory cytokine TNF-a may be beneficial. Pentoxifyline, a xanthine agent known to inhibit the production of TNF-a and to prevent apoptosis, has been studied in PPCM. In a prospective study of 59 women with PPCM, 30 treated with pentoxifyline 400 mg three times a day in addition to standard therapy of heart failure, a significant improvement of LV function > 10%, and end-diastolic dimensions, a reduction of mortality rate, and greater increase in functional status, compared with the control group were found (Sliwa et al., 2002).

Bromocriptine therapy

Considering the observations that strongly suggest prolactin cleavage as a specific mechanism for the development of PPCM, specific inhibition of its secretion with bromocriptine, a dopamine D2 receptor agonist, is promising. Thus, bromocriptine might represent a novel specific therapeutic approach to either prevent or treat patients with acute PPCM (Hilfiker-Kleiner et al., 2008). Several case reports demonstrated recovery of LV function after treatment with bromocriptine (Elkayam & Goland, 2010; Habedank, 2008; Hilfiker-Kleiner, 2007b; Jahns, B.G., 2008; Meyer, 2010). Very recently, Sliwa et al. reported the results of a prospective, single-center, randomized, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard therapy with or without bromocriptine for 8 weeks. The addition of bromocriptine appeared to significantly improve LV function (27% at baseline, to 58% at 6 months, p=0.012), and a composite clinical outcome (Sliwa et al., 2010b). Analyzing these data together, Fett remarked that important details of studies design must be corrected for appropriate results. The author proposes some essential conditions to conduct further trials. Patients included in such trials may be best to have serum cathepsin-D activation, positive test for serum 16-kDa prolactin, and very important, to accept lactation suppression while assuring alternative newborn nutrition (Fett, 2010). Also, Fett suggests that bromocriptine treatment should be limited to those patients with LV ejection fraction < 35%, because of poor prognosis with standard therapy in this category. Concerning the safety of bromocriptine in early postpartum women, there are several reports of myocardial infarction (Hopp et al., 1996), while adding adequate anticoagulant therapy, thromboembolism is not reported in such patients (Meyer, 2010; Sliwa, 2010b). Secondly, there are many reports on myocardial infarction in early postpartum independent from bromocriptine administration (Hilfiker-Kleiner et al., 2008). The results of these studies may represent breakthroughs in the understanding of PPCM pathogenesis, and in the development of a new specific therapy for this clinical entity. But, at the present time, a large, prospective, multicenter, randomized trial is needed to allow bromocriptine extensive use. Such a trial is on-going in Haiti and South Africa (Pyatt & Dubey, 2011).

Other proposed therapies are based on the potential of several agents, such as calcium channel antagonists, statins, interferon-P, monoclonal antibodies, or methods (immunoadsorbtion, apheresis) to influence pro-inflammatory cytokines in acute myocarditis (Ramaraj & Sorrell, 2009).

Main concern

How to treat better? The current medical strategies are not always safe enough for maternal prognostic. There is no clear evidence for the beneficial effect of standard therapy on the recovery of cardiac function in patients with PPCM. As the cause of PPCM is still unknown, no specific therapy has been established to treat this condition.

Implications for research

As the excessive prolactin hypothesis seems to be specific for PPCM, a specific therapeutic intervention using bromocriptine should be tested in an extensive, controlled manner.

Specific management of peripartum cardiomyopathy

In addition to treatment of heart failure, an obstetrical plan for close monitoring must be developed when PPCM is diagnosed during pregnancy. A collaborative approach, including the obstetrician, cardiologist, anesthesiologist, and neonatologist is essential to optimal care. Serial clinical assessment should be scheduled during late pregnancy. Antenatal testing, such as non-stress test and amniotic fluid index, or biophysical profile is also recommended (Cruz et al., 2010). A baseline ultrasound scan is best to be performed during pregnancy for monitoring the fetus (Sliwa et al, 2010a). If patient is stable, responsive to medical therapy, the pregnancy should be allowed to go to term. The medical team should discuss the delivery mode, primarily considering the mother’s benefit. Spontaneous vaginal delivery is preferred in stable women with healthy fetus. For patients with newly diagnosed PPCM before delivery, labor should be induced, or a cesarean section must be planned if mothers are critically ill, or LV function is deteriorating rapidly, or with obstetrical indication (Murali, 2005). After delivery, strict maintenance of fluid status is recommended, using diuretic therapy to prevent volume overload, as fluids are resorbed into the intravascular space (Cruz et al., 2010). Continuous invasive maternal monitoring, including an arterial line and pulmonary catheter, for adequate assessment of patient’s hemodynamic status and guide management, as well as continuous fetal cardiotocography are strongly recommended (de Beus et al., 2003). Antenatal medication may be administered, except heparin which should be discontinued at least 12 hours prior to delivery, and resumed 12-24 hours after delivery, with obstetrician and anesthesiologist’s permission. Continuous analgesia and anesthesia are needed to minimize further cardiac stress and pain relief, and should be performed with careful specialized monitoring. Epidural analgesia is preferred during labor, as it stabilizes cardiac output through a sympathectomy-induced afterload reduction (Sliwa et al., 2010a). Continuous spinal anesthesia, with epidural analgesia are recommended for cesarean section, as the hemodynamic stability may be more easily maintained (Murali et al., 2005). If general anesthesia is required, drugs with myocardial depressant effect should be avoided, and induction and maintenance with a high-dose opioid technique is preferred. The second stage of labor can cause maximum hemodynamic and oxidative cardiac stress, so these periods must be shortened using a vacuum device or low forceps. A single dose of intramuscular oxytocin can optimally manage the third stage of labor; ergometrine is forbidden (Oakley et al., 2003).Breastfeeding should be avoided in patients with PPCM, although several drugs have been tested and are safe.


Predictive factors and follow-up

Very few studies have been done to assess the long-term survival and recovery outcomes in PPCM. Although PPCM is a form of dilated cardiomyopathy, a characteristic feature is that a higher rate of spontaneous recovery of LV function occurs. A subset of women with PPCM, despite using an optimal medical treatment, follows a rapid and irreversible course, associated with persistent LV dysfunction, severe heart failure, or premature death. Whitehead et al. reported that in USA 30-50% of patients return to normal within 6 months post partum (Whitehead et al., 2003), while a single centre prospective study, conducted in South Africa, described only a 23% recovering rate of LV function, despite optimal therapy with ACEI and p blockers (Sliwa et al., 2006b). The same author reported a 32% 6-month mortality rate in case series from South Africa (Sliwa et al., 2000). In another study, in Haitian women, with a mean follow-up period of 5 years, the rate of recovery was 31.5%, while mortality rate was 15 %. An important finding of this study was that the recovery to normal LV function can occur later, after 2-3 years after diagnosis, so it is not limited to the first 6-12 months (Fett et al., 2005a). A recent study describes similar rates of LV function recovery and survival in women from USA, Haiti, and South Africa, probably related to improvements in medical therapy, and to the aggressive use of cardioverters in the non-American studied population (Modi et al., 2009). Analyzing the predictive factors for long- term prognostic, Duran et al. concluded NYHA functional class, QRS duration, and LV parameters at the time of diagnosis were important predictors. Initial cut-off values of < 5.5 cm for LV end-systolic diameter, and > 27% for LV ejection fraction were identified to predict complete recovery of LV function, while QRS duration on electrocardiogram > 120 ms was a predictor for mortality (Duran et al., 2008). Reviewing 182 patients with PPCM for major adverse events and death, Goland et al. also demonstrated that in all cases there was a strong relation with severe LV dysfunction, non-Caucasian race, and a delayed diagnosis (Goland et al., 2009). These findings complete previous observations about the relation between the severity and persistence of LV dysfunction and the incidence of morbidity and mortality. A LV ejection fraction > 30% at the time of diagnosis might be a predictor for recovery (Elkayam et al., 2005). LV end-diastolic diameter > 6 cm and fractional shortening < 20% are proposed as risks factors for long-term prognosis, as are correlated with a more than threefold higher risk of progressing to persistent LV dysfunction later on (Chapa, 2005; Wittin, 1997). Recently, Baruteau et al. discussed the potential significance of cardiac MRI in prognostic stratification, by assessing LV size, function, and contractile reserve, as well as prognostic MRI factors identified in myocarditis for "myocarditis-like" forms of PPCM (end-diastolic volume, septal localization, and total amount of late gadolinium enhancement at initial time) (Baruteau et al., 2010). Other authors propose immunological mediators and markers of apoptosis to predict outcome. Elevated C-reactive protein and Fas/APO-1 were reported to be related to decreased LV function and mortality (Sliwa et al., 2006b). These perspectives remain to be evaluated by further studies.

In summary, the prognosis varies according to geographical region, and probably, the most important predictor remains the recovery of LV systolic function.

Follow-up of patients with PPCM is similar with that for other forms of cardiomyopathy and LV systolic dysfunction. Patients should be monitored regularly to assess clinical course, complications, LV systolic dysfunction and dimensions, and the response to treatment. Considering that the recovery interval is not restricted to the first 6-12 months postpartum, it is strongly recommended to continue treatment and follow-up for a long period of time to achieve best results (Fett, 2009). However, the optimal period remains unknown. At the present time, echocardiography is the most important tool for serial assessment. In the first several weeks after diagnosis, an echocardiogram should be performed to assess the level of LV function. After that, it should be repeated at about every 6-12 months until recovery is confirmed, or a plateau is reached (Sliwa et al., 2006a). Dobutamine stress echocardiography may be performed to assess the potential for LV function recovery, by measuring the inotropic contractile reserve (Dorbala et al., 2005). The technique is useful especially when LV systolic function is normal, and the contractile reserve remains decreased (Lampert et al., 1997).

Subsequent pregnancies, risk of relapse

One of the most important issues in PPCM is the safety of subsequent pregnancies. Even after the full recovery of LV function, the risk of relapse might be present. In Haitian women, Fett et al. described a rate of recurrence of 53% with subsequent pregnancy. In a retrospective study in USA, it was observed that subsequent pregnancy was associated with the recurrence of heart failure, regardless the previous LV function. However, in women who had a normal LV function, the rate of heart failure was 21% compared with 44% in women who had altered function. Also, all deaths occurred in the last group. Furthermore, recovery of LV function was more frequent in patient with an ejection fraction > 30% at diagnosis of disease (Elkayam et al., 2001). Another retrospective study confirmed a better prognosis for subsequent pregnancy in women who had a higher ejection fraction at diagnosis. However, no relation between ejection fraction and worsening clinical symptoms was found in 29% of patients. Also, a baseline ejection fraction of < 25% at index pregnancy was associated with a higher rate of cardiac transplant (Habli et al., 2008). According to these data, it is especially important to provide the most appropriate information about a potential relapse with subsequent pregnancy. LV systolic function seems to be the key prognostic factor when counseling women with PPCM about the further risks. Individual planning might be done after an echocardiogram was performed:

- if LV ejection fraction is < 25% at diagnosis or incompletely recovered, the advice should be against further pregnancy (Sliwa et al., 2010a);

- even if LV function is normal, the patients ought to have stress-echocardiography:

• women with an abnormal LV inotropic response to dobutamine have a moderate risk of relapse and pregnancy is not recommended;

• women with complete recovery on both echocardiography and dobutamine stress test can be informed about the low rate of complications. In this group, despite a 35% rate of risk of recurrence, pregnancy can be completed in almost all cases (Pyatt & Durbey, 2011).

In postpartum period, it is imperative to give contraceptive counseling and educate the patients about the existent alternatives. Women who had PPCM should avoid pregnancy, best until LV function has recovered. The combined oral contraceptives, containing estrogens and progestins are contraindicated, as estrogens increase the thromboembolic risk. Progesterone contraception alone is permitted (Thorne et al., 2006). Barrier methods are not recommended as they have a high rate of failure. Intrauterine systems are the most efficient and safe methods of contraception. Sterilization methods, including vasectomy, tubal ligation, and insertion of intratubal stents may be considered (Sliwa et al., 2010a). At the present time, no protocols for decision-making when counseling women with PPCM about risks of subsequent pregnancies are established. For this reason, it is advisable that every women who experienced PPCM, to be considered at risk, and to be closely monitored by the medical team, in a high-risk obstetrical center.

Main concern

What is the course and prognosis of the disease? With the sparse knowledge in this field, the individual outcome is difficult to predict.

Implications for research

Novel diagnostic strategies, based on improved understanding of pathophysiology and molecular basis of PPCM, should be developed to enhance both diagnostic and prognostic utility. Collecting data from the children born to affected women should be an important priority.

Conclusions and future directions

Since its original description, peripartum cardiomyopathy remains a challenge for both diagnosis and treatment. Although several advances have been made to further the knowledge, the condition is still considered a cardiomyopathy of unknown cause. In terms of future research, a better understanding of its molecular basis and fundamental underlying mechanisms, including potential genetic contribution and life-style aspects, is needed. From a clinical perspective, the ability to identify patients at risk to develop the disease is mandatory. Despite current definition, PPCM can remain undiagnosed until it’s too late, as some important issues, such as, its rarity in developed countries, the heterogenity of studied populations, and the lack of adherence to diagnostic guidelines, are not resolved. Collaborative, multicentre prospective, well-conducted, population-based trials are required for the development of national and international health policies on prevention, early diagnosis and management, and standard therapeutic control. The Peripartum Cardiomyopathy Netwotk is a NIH-funded North America ongoing trial conducted in order to address some of unresolved issues, as long as the Haitian PPCM Registry is the only existing population-based registry in the world (Fett, 2005a, 2010). Novel diagnostic strategies and biomarkers are potential candidates that should be validated in large clinical trials. Cardiac MRI and prolactin production might provide valuable diagnostic and prognostic information. Also, it would be ideal to have some specific therapeutic strategies. The most realistic candidate seems to be bromocriptine, although potential new treatments, including immune-modulatory therapy, apheresis, and antiviral agents might have a decisive role. Considering all these data, it is important for clinicians to be aware of this condition, so that unnecessary delays in diagnosis can be avoided, and appropriate therapy can be prescribed in a timely fashion. With current technology, clinicians and researchers are now connected, and new bases for multidisciplinary collaboration might be developed.

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