Review
Improving outcomes in peripartum cardiomyopathy Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/08/15 For personal use only.
Expert Rev. Cardiovasc. Ther. 13(6), 665–671 (2015)
Jonathan R Dalzell*1,2, Jane A Cannon3, Joanne Simpson3, Roy S Gardner1 and Mark C Petrie1 1 Scottish Advanced Heart Failure Unit, Golden Jubilee National Hospital, Glasgow, G81 4DY, UK 2 Department of Advanced Heart Failure, Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield, London, UB9 6JH, UK 3 British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK *Author for correspondence: Tel.: +44 014 1330 2237 Fax: +44 014 1330 6955 [email protected]
informahealthcare.com
Peripartum cardiomyopathy (PPCM) is a rare condition with a diverse spectrum of potential outcomes, ranging from frequent complete recovery to fulminant heart failure and death. The pathogenesis of PPCM is not well understood, and relatively little is known about its incidence and prevalence. PPCM is often under-recognised in the clinical setting. Early investigation and diagnosis with subsequent expert management may improve outcomes. The development of registries will allow this condition to be better characterised and may help answer crucial questions regarding its optimal medical and surgical management. This paper reviews the potential approaches to improve outcomes in patients with PPCM. KEYWORDS: heart failure . peripartum cardiomyopathy . pregnancy . prolactin . transplantation . ventricular assist device
Peripartum cardiomyopathy (PPCM) is a potentially devastating complication of pregnancy associated with heart failure (HF) due to left ventricular systolic dysfunction, thromboembolism and malignant arrhythmias. It is currently defined by the European Society of Cardiology working group on PPCM as follows: ‘An idiopathic cardiomyopathy presenting with HF secondary to left ventricular systolic dysfunction toward the end of pregnancy or in the months following delivery, where no other cause of HF is found. It is a diagnosis of exclusion. The left ventricle (LV) may not be dilated, but the ejection fraction (EF) is nearly always reduced below 45%’ [1]. The diagnosis of PPCM is, therefore, currently one of exclusion [1,2]. Given its apparent rarity, the epidemiology, pathophysiology, risk factors and optimal management of PPCM remain unclear. Epidemiological studies, the majority of which are relatively small and singlecentred, have been undertaken in the USA [3–6], Haiti [7], Malaysia [8], Niger [9] and Nigeria [10] and they have given widely varying results. These investigations differ with regard to the definition of PPCM used, population sizes, clinical and echocardiographic assessment and whether or not alternative causes of HF were excluded. Despite this, there appears to be a marked geographical and ethnic variation in the incidence of PPCM, with a higher incidence seen in Haiti and Africa and in patients of African-American ethnicity. The prognosis following a diagnosis of 10.1586/14779072.2015.1040767
PPCM appears to be better than other causes of dilated cardiomyopathy [11]. Studies that differ widely with regard to size, population and follow-up duration have reported varying mortality rates from 0 to 30% [7,12–27]. These relatively favourable mortality rates may reflect the potential for recovery of LV function, with rates of recovery between 23 and 85% having been described in several studies of patients receiving contemporary therapy (TABLE 1). Improvements in the outcomes of PPCM will be driven by an increased awareness and understanding of the condition. In the short to medium term, the crucial goals are: 1. Improvements in medical therapy, especially with regards to clarification of the potential impact of antagonism of the putative PPCMspecific 16 kDa prolactin pathway (see below). 2. Increased awareness of PPCM as a potential diagnosis among all clinicians managing patients with PPCM, as well as the appreciation of the importance of prompt onward specialist referral. Decisions around the care of patients with PPCM are often challenging and subtle. Complex decisions include timing of implantable cardioverter defibrillators (ICDs), cardiac resynchronisation therapy (CRT), left ventricular assist devices (LVADs) and cardiac transplantation. Counselling for future pregnancies and management during such pregnancies require a skilled multidisciplinary approach.
2015 Informa UK Ltd
ISSN 1477-9072
665
Review
Dalzell, Cannon, Simpson, Gardner & Petrie
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/08/15 For personal use only.
Table 1. Reported rates of peripartum cardiomyopathy mortality/ recovery/cardiac transplant/mechanical circulatory support. Follow-up
Mortality
LV recovery
Transplant
MCS
23 months (mean)
9/100 (9%)
54/100 (54%)
4/100 (4%)
0
[12]
2.2 years (mean)
15/98 (15.3%)
26/92 (28.3%) ns
ns
[7]
8.6 years (median)
3/42 (7.1%)
ns (43%)
0
[13]
6 months
3/43 (7%)
25/38 (65.8%) 0
0
[14]
6 months
8/29 (27.6%)
10/29 (34.4%) ns
ns
[15]
6 months
15/100 (15%)
23/100 (23%)
0
0
[16]
19 months (mean)
13/182 (7.1%)
ns (49%)
11/182 (6%)
4/182 (2.2%) LVAD – 1 BiVAD – 1
[17]
4.5 months
10/33 (30.3%)
8/33 (24.2%)
2/33 (6.1%)
ns
[18]
43 months (mean)
0/49 (0%)
22/49 (44.9%) 5/49 (10.2%)
ns
[19]
46 months (median)
0/32 (0%)
13/32 (40.6%) 2/32 (6.3%)
ns
[20]
35 mean
11/100 (11%)
42/100 (42%)
2/100 (2%)
1/100 (1%)
[21]
ns
7/535 (1.3%)
ns
0
0
[22]
6 months
2/96 (2.1%)
82/96 (85.4%) 7/96 (7.3%)
1/96 (1%)
[23]
77 months (mean)
1/12 (8.3%)
6/9 (66.7%)
ns
1/12 IABP (8.3%)
[24]
6 months
21/162 (13.0%)
30/141 (21.3%)
ns
ns
[25]
6 months
1/12 (8.3%)
6/12 (50.0%)
1/12 (8.3%)
0
[26]
Minimum 30 months
10/42 (23.8%)
20/42 (47.6%) 0
2/42 (4.8%) (both IABP)
[27]
Patients retrospectively studied over 7-year time frame (mean ns)
1.3% (in hospital)
ns
1.5%
3/42 (7.1%)
Ref.
ICDs & CRT
0.5%
[3]
BiVAD: Biventricular assist device; IABP: Intra-aortic balloon pump; LV: Left ventricular; LVAD: Left ventricular assist device; MCS: Mechanical circulatory support; ns: Not significant.
3. Improved prognostic ability which may allow certain treatment (e.g., ICD, LVAD or transplantation) to be appropriately and promptly targeted towards specific subsets of patients. Improvements in medical treatment Pharmacological treatment
Patients with PPCM are currently managed according to the established HF guidelines with regard to pharmacological agents [28] with the caveat that angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid 666
receptor antagonists are contraindicated in pregnancy and during breast feeding. Given the apparent association of PPCM with thromboembolism, anticoagulation is recommended in patients with a left ventricular ejection fraction (LVEF)
Improving outcomes in peripartum cardiomyopathy Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/08/15 For personal use only.
Expert Rev. Cardiovasc. Ther. 13(6), 665–671 (2015)
Jonathan R Dalzell*1,2, Jane A Cannon3, Joanne Simpson3, Roy S Gardner1 and Mark C Petrie1 1 Scottish Advanced Heart Failure Unit, Golden Jubilee National Hospital, Glasgow, G81 4DY, UK 2 Department of Advanced Heart Failure, Transplantation and Mechanical Circulatory Support, Royal Brompton & Harefield NHS Foundation Trust, Harefield, London, UB9 6JH, UK 3 British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK *Author for correspondence: Tel.: +44 014 1330 2237 Fax: +44 014 1330 6955 [email protected]
informahealthcare.com
Peripartum cardiomyopathy (PPCM) is a rare condition with a diverse spectrum of potential outcomes, ranging from frequent complete recovery to fulminant heart failure and death. The pathogenesis of PPCM is not well understood, and relatively little is known about its incidence and prevalence. PPCM is often under-recognised in the clinical setting. Early investigation and diagnosis with subsequent expert management may improve outcomes. The development of registries will allow this condition to be better characterised and may help answer crucial questions regarding its optimal medical and surgical management. This paper reviews the potential approaches to improve outcomes in patients with PPCM. KEYWORDS: heart failure . peripartum cardiomyopathy . pregnancy . prolactin . transplantation . ventricular assist device
Peripartum cardiomyopathy (PPCM) is a potentially devastating complication of pregnancy associated with heart failure (HF) due to left ventricular systolic dysfunction, thromboembolism and malignant arrhythmias. It is currently defined by the European Society of Cardiology working group on PPCM as follows: ‘An idiopathic cardiomyopathy presenting with HF secondary to left ventricular systolic dysfunction toward the end of pregnancy or in the months following delivery, where no other cause of HF is found. It is a diagnosis of exclusion. The left ventricle (LV) may not be dilated, but the ejection fraction (EF) is nearly always reduced below 45%’ [1]. The diagnosis of PPCM is, therefore, currently one of exclusion [1,2]. Given its apparent rarity, the epidemiology, pathophysiology, risk factors and optimal management of PPCM remain unclear. Epidemiological studies, the majority of which are relatively small and singlecentred, have been undertaken in the USA [3–6], Haiti [7], Malaysia [8], Niger [9] and Nigeria [10] and they have given widely varying results. These investigations differ with regard to the definition of PPCM used, population sizes, clinical and echocardiographic assessment and whether or not alternative causes of HF were excluded. Despite this, there appears to be a marked geographical and ethnic variation in the incidence of PPCM, with a higher incidence seen in Haiti and Africa and in patients of African-American ethnicity. The prognosis following a diagnosis of 10.1586/14779072.2015.1040767
PPCM appears to be better than other causes of dilated cardiomyopathy [11]. Studies that differ widely with regard to size, population and follow-up duration have reported varying mortality rates from 0 to 30% [7,12–27]. These relatively favourable mortality rates may reflect the potential for recovery of LV function, with rates of recovery between 23 and 85% having been described in several studies of patients receiving contemporary therapy (TABLE 1). Improvements in the outcomes of PPCM will be driven by an increased awareness and understanding of the condition. In the short to medium term, the crucial goals are: 1. Improvements in medical therapy, especially with regards to clarification of the potential impact of antagonism of the putative PPCMspecific 16 kDa prolactin pathway (see below). 2. Increased awareness of PPCM as a potential diagnosis among all clinicians managing patients with PPCM, as well as the appreciation of the importance of prompt onward specialist referral. Decisions around the care of patients with PPCM are often challenging and subtle. Complex decisions include timing of implantable cardioverter defibrillators (ICDs), cardiac resynchronisation therapy (CRT), left ventricular assist devices (LVADs) and cardiac transplantation. Counselling for future pregnancies and management during such pregnancies require a skilled multidisciplinary approach.
2015 Informa UK Ltd
ISSN 1477-9072
665
Review
Dalzell, Cannon, Simpson, Gardner & Petrie
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/08/15 For personal use only.
Table 1. Reported rates of peripartum cardiomyopathy mortality/ recovery/cardiac transplant/mechanical circulatory support. Follow-up
Mortality
LV recovery
Transplant
MCS
23 months (mean)
9/100 (9%)
54/100 (54%)
4/100 (4%)
0
[12]
2.2 years (mean)
15/98 (15.3%)
26/92 (28.3%) ns
ns
[7]
8.6 years (median)
3/42 (7.1%)
ns (43%)
0
[13]
6 months
3/43 (7%)
25/38 (65.8%) 0
0
[14]
6 months
8/29 (27.6%)
10/29 (34.4%) ns
ns
[15]
6 months
15/100 (15%)
23/100 (23%)
0
0
[16]
19 months (mean)
13/182 (7.1%)
ns (49%)
11/182 (6%)
4/182 (2.2%) LVAD – 1 BiVAD – 1
[17]
4.5 months
10/33 (30.3%)
8/33 (24.2%)
2/33 (6.1%)
ns
[18]
43 months (mean)
0/49 (0%)
22/49 (44.9%) 5/49 (10.2%)
ns
[19]
46 months (median)
0/32 (0%)
13/32 (40.6%) 2/32 (6.3%)
ns
[20]
35 mean
11/100 (11%)
42/100 (42%)
2/100 (2%)
1/100 (1%)
[21]
ns
7/535 (1.3%)
ns
0
0
[22]
6 months
2/96 (2.1%)
82/96 (85.4%) 7/96 (7.3%)
1/96 (1%)
[23]
77 months (mean)
1/12 (8.3%)
6/9 (66.7%)
ns
1/12 IABP (8.3%)
[24]
6 months
21/162 (13.0%)
30/141 (21.3%)
ns
ns
[25]
6 months
1/12 (8.3%)
6/12 (50.0%)
1/12 (8.3%)
0
[26]
Minimum 30 months
10/42 (23.8%)
20/42 (47.6%) 0
2/42 (4.8%) (both IABP)
[27]
Patients retrospectively studied over 7-year time frame (mean ns)
1.3% (in hospital)
ns
1.5%
3/42 (7.1%)
Ref.
ICDs & CRT
0.5%
[3]
BiVAD: Biventricular assist device; IABP: Intra-aortic balloon pump; LV: Left ventricular; LVAD: Left ventricular assist device; MCS: Mechanical circulatory support; ns: Not significant.
3. Improved prognostic ability which may allow certain treatment (e.g., ICD, LVAD or transplantation) to be appropriately and promptly targeted towards specific subsets of patients. Improvements in medical treatment Pharmacological treatment
Patients with PPCM are currently managed according to the established HF guidelines with regard to pharmacological agents [28] with the caveat that angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid 666
receptor antagonists are contraindicated in pregnancy and during breast feeding. Given the apparent association of PPCM with thromboembolism, anticoagulation is recommended in patients with a left ventricular ejection fraction (LVEF)
