What’s New with Peripartum Cardiomyopathy? Albert Hans P. Bautista, MD, FPCP, FPCC The Medical City Session: Cardiomyopathy and Cor Pulmonale Friday, May 25, 2012; 2:00-2:30 Sapphire B, Crowne Plaza Hotel Philippine Heart Association 43 rd Annual Convention & Scientific Meeting Bringing Global Trends in Cardiology Closer to Home
Philippine Heart Association 43 rd Annual Convention & Scientific Meeting Bringing Global Trends in Cardiology Closer to Home. What’s New with Peripartum Cardiomyopathy?. Albert Hans P. Bautista, MD, FPCP, FPCC The Medical City. Session: Cardiomyopathy and Cor Pulmonale - PowerPoint PPT Presentation
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What’s New with Peripartum
Cardiomyopathy?Albert Hans P. Bautista, MD, FPCP, FPCC
The Medical City
Session: Cardiomyopathy and Cor Pulmonale Friday, May 25, 2012; 2:00-2:30 Sapphire B, Crowne Plaza Hotel
Bringing Global Trends in Cardiology Closer to Home
2
- Received honorarium for lectures on various cardiovascular topics - hypertension, ACS, anti-platelet /anti-coagulation & CHF for various pharmaceutical companies.
- Received research grants or honorarium for various clinical trials on hypertension, anti-platelet, anti-coagulation, ACS & CHF patients for various pharmaceutical companies.
- Member of the Advisory Board for Thrombosis of Sanofi
DisclosuresDisclosures
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- Review the cardiovascular changes in pregnancy
- Pathophysiology of PPCM
- History, PE and Diagnosis of PPCM
- Treatment of PPCM
Session OutlineSession OutlineWhat’s New in PERIPARTUM
CARDIOMYOPATHY?
4
- Review the cardiovascular changes in pregnancy
- Pathophysiology of PPCM
- History, PE and Diagnosis of PPCM
- Treatment of PPCM
Session OutlineSession OutlineWhat’s New in PERIPARTUM
CARDIOMYOPATHY?
5
- To meet the increased metabolic demands of both the mother and fetus1,2 (evident by 5th to 8th wk, peak by late 2nd trimester)
> Increased blood volume (40%)> Increased CO (30-50%) 80% early postpartum> Decreased SVR & BP (active vasodilation)> Increased LV size (30%, dilatation)
- Hypercoagulopathy1
> Increased coagulation factors, fibrinogen & platelet adhesiveness> Risk for thrombo-embolism from venous stasis due to obstructing uterus
Cardiovascular Changes in PregnancyCardiovascular Changes in Pregnancy
2) Oakley C et al Ed. Heart Disease in Pregnancy 2nd Ed. Massachusetts, Blackwell Publishing 2007:6-17
1) ESC Guidelines on the management of cardiovascular diseases during pregnancy. European Heart Journal (2011) 32, 3147–3197
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- Idiopathic cardiomyopathy presenting with heart failure 2ndary to LV systolic dysfunction from 1 month antepartum, up to 5 months after delivery, when no other causes of heart failure is evident3
- Incidence of 1:3004 to 1:40005 pregnancies- Predisposing factors:5, 6, 7
> Multiparity > multiple births> Smoking, diabetes> Pregnancy complicated by pre-eclampsia, eclampsia or hypertension> Advanced age or teenage pregnancy
5) Pearson G et al. National Heart, Lung and Blood Institute and Office of Rare Diseases (National Institute of Health) Workshop Recommendations and review. JAMA. 2000; 283 (9): 1183-11886) Sliwa K et al. Peripartum Cardiomyopathy. Lancet. 2006; 368 (9536): 687-6937) Demakis JG et al. Natural course of peripartum cardiomyopathy. Circulation. 1971; 44 (6): 238-244
3) Elliott P, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on myocardial and pericardial diseases. Eur Heart J 2008; 29: 270-2764) Fett JD et al. Five year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc 2005; 80 (12): 1602-1606
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- Etiology8 (Plausible etiologic mechanisms):> Myocarditis> Apoptosis & inflammation> Abnormal immune response to pregnancy (Chimerism)> Maladaptive response to hemodynamic stresses of
9) Midei MG et al. Peripartum myocarditis and cardiomyopathy. Circulation. 1990; 81: 922-928
12) Sliwa K et al. Peripartum Cardiomyopathy: analysis of clinical outcome, LV function, plasma levels of cytokines and Fas/Apo-1. J Am Coll Cardiol. 2000; 35 (3): 701-705
10) Rizeq MN, et al. Incidence of myocarditis in peripartum cardiomyopathy. Am J Cardiol. 1994; 74: 474-477
11) Melvin K, et al. Peripartum cardiomyopathy due to myocarditis. N Engl J Med. 1982; 307 (12): 731-734
13) van Hoeven KH, et al. Peripartum versus idiopathic cardiomyopathy in young women – a comparison of clinical, pathological and prognostic factors. Int J Cardiol 1993; 40 (1): 57-65
10
Etiology (Plausible etiologic mechanisms):
- Abnormal immune response to pregnancy (chimerism)> Fetal micro-chimerism (harboring) of fetal cells in maternal circulation14
> Natural immuno-suppression lost after delivery & if the fetal cell 5,6,14,15,16
happen to be on the cardiac tissues pathologic autoimmune response PPCM
- Maladaptive response to hemodynamic stress of pregnancy> inc bld vol, inc CO, inc preload, dec afterload brief and reversible LV
hypertrophy to meet the demands of pregnancy> ”transient LV dysfunction” during the 3rd trimester and early postpartum
resolves shortly after birth16
> There is an exaggerated decrease in LV function when these hemodynamic changes occur5
14) Ansari AA et al. Autoimmune mechanism as basis for human peripartum cardiomyopathy. Clin Rev Allergy Immunol. 2002; 23: 301-324
5) Pearson G et al. National Heart, Lung and Blood Institute and Office of Rare Diseases (National Institute of Health) Workshop Recommendations and review. JAMA. 2000; 283 (9): 1183-1188
16) Ntusi NB, et al. Aetiology and risk factors of peripartum cardiomyopathy: a systematic review. Int J Cardiol. 2009; 131 (2): 168-179
15) Hilfiker-Kleiner D, et al. Peripatum cardiomyopathy: recent insight in its pathophysiology. Trends Cardiovasc Med. 2008; 18 (5): 173-179
17) Hilfiker-Kleiner D et al. A cathepsin D-cleaved 16kDa form of prolactin mediates peripartum cardiomayopathy. Cell. 2007; 128 (3): 589-600
18) Forster O, et al. Reversal of IFN-gamma, oxLDL, and prolactin serum levels correlate with clinical improvement in patients with peripartum cardiomyopathy. Eur J Heart Fail. 2008; 10: 861-868
> NVE > Soft S1, S3, S4, m changes in m- Lungs - Extremities
> Rales (bibasal) > bipedal edema- Abdomen
> Hepatomegaly, hepato-jugular reflux- Arrhythmia i.e. AF- Embolic events due to dysfunctional dilated LV
Peripartum CardiomyopathyPeripartum Cardiomyopathy: History & PE History & PE
5) Pearson G et al. National Heart, Lung and Blood Institute and Office of Rare Diseases (National Institute of Health) Workshop Recommendations and review. JAMA. 2000; 283 (9): 1183-1188
19) Ro A et al. Peripartum cardiomyopathy. Cardiac Rev 2006; 14 (1): 35-4220) Ramaraj R et al. Peripartum cardiomyopathy: causes, diagnosis and treatment. Clev Clin J Med. 2009; 76 (5): 289-29621) Williams J, et al. Critical Care in Obstetrics: pregnancy-specific conditions. Best Prac Res Clin Obstet Gynaecol. 2008; 22 (5): 825-846
22) Hibbard JU, et al. A modified definition for peripartum cardiomyopathy and prognosis based on echocardiography. Obstet Gynecol 1999; 94: 311-316
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Peripartum Care: 1
- joint Obstetric and Cardiac care; perinat/neonat- consider urgent termination of pregnancy in refractory HF- vaginal delivery preferred, C/S as obstetrical indication- lumbar epidural analgesia- LL recumbent during labor, avoid to “push,” assisted by
1) ESC Guidelines on the management of cardiovascular diseases during pregnancy. European Heart Journal (2011) 32, 3147–3197
16
Peripartum Care: 5, 21, 23
- HF treatment as per guidelines- similar to other forms of heart failure- careful attention to a) fetal safety b) drug excretion c) drug metabolism- Goals:
> Improve hemodynamic status> Minimize signs & symptoms> Optimize long term outcome
- Focus:> reducing preload and afterload> increasing/improving cardiac inotropy
5) Pearson G et al. National Heart, Lung and Blood Institute and Office of Rare Diseases (National Institute of Health) Workshop Recommendations and review. JAMA. 2000; 283 (9): 1183-1188
21) Williams J, et al. Critical Care in Obstetrics: pregnancy-specific conditions. Best Prac Res Clin Obstet Gynaecol. 2008; 22 (5): 825-846
23) Tidswell M, et al. Peripartum cardiomyopathy. Critical Care Clin. 2004; 20: 777-788
17
Peripartum Care: 8
- Hospitalization due to a) hypotension b) worsening HF c) altered mental status d) inc work of breathing (pul edema)- Management:
8) Johnson-Coyle L, et al. Peripartum cardiomyopathy: Review and Practice Guidelines. Am J Critical Care 2012; 21 (2): 89-98
24) Homma S et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012; 366 (20): 1859-1869
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- Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhtyhm Homma S et al. N Engl J Med 2012; 366(20): 1859-69
- WARCEF Warfarin vs Aspirin in Reduced Cardiac Ejection Fraction
- Hypothesis: Is warfarin superior to aspirin alone for patients with heart failure who are in sinus rhythm?
- P : 2,305 HF patients < 35% with sinus rhythm I : Warfarin (1,163) vs ASA 325mg (1,142) O : First event of composite endpoint of ischemic stroke, intracerebral haemorrhage and death M : double blind randomized clinical trial, W: INR=2-3, A: 325mg OD
Peripartum CardiomyopathyPeripartum Cardiomyopathy: WARCEF STUDY WARCEF STUDY
24) Homma S et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012; 366 (20): 1859-1869
20
- P : 2,305 HF patients < 35% with sinus rhythm I : Warfarin (1,163) vs ASA 325mg (1,142) O : First event of composite endpoint of ischemic stroke, intracerebral haemorrhage and death M : double blind randomized clinical trial, W: INR=2-3, A: 325mg OD- Results: > Primary Outcome: HR= 0.93 (0.7-1.10) NS > Ischemic Stroke (W): HR= 0.52 (0.33-0.82) p=0.005 > Major Haemorrhage (W): HR=2.1 (1.4-3.1) p<0.001- Conclusion: > Patients w/ HF + sinus rhythm warfarin reduces risk of ischemic stroke but at a cost of increased major haemorrhage > no significant difference between ASA and warfarin in the composite endpoint of death, ischemic stroke and IC bleed or HF hospitalization > No compelling reason to use warfarin over aspirin for patients with systolic heart failure and sinus rhythm
Peripartum CardiomyopathyPeripartum Cardiomyopathy: WARCEF STUDY WARCEF STUDY
24) Homma S et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012; 366 (20): 1859-1869
21
Postpartum Care:- Medications:20
7) Others: in refractory heart failure, limited data a) pentoxifylline – improve outcomes, LV function/ S&S b) IV immonoglobulin – improved EF, reduced levels of inflammatory cytokines c) immunosuppressive therapy – no proven role but could be tried in proven viral myocarditis d) Bromocriptine*25
20) Ramaraj R et al. Peripartum cardiomyopathy: causes, diagnosis and treatment. Clev Clin J Med. 2009; 76 (5): 289-29625) Sliwa K et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof of concept pilot study. Circulation. 2010; 121: 1465-1473
22
- Evaluation of Bromocriptine in the Treatment of Acute Severe Peripartum Cardiomyopathy (A Proof of Concept Pilot Study)
Sliwa K et al. Circulation. 2010; 121: 1465-1473
- Hypothesis: Prolactin (mainly 16-Kda angiostatic and proapoptotic form) initiates and rives PPCM and that early pharmacologic blockade of prolactin with bromocritptine may improve the patients’ condition before irreversible cell damage sets in, looked into as HF therapy to improve LVEF, functional class and survival in women with acute severe PPCM.
- P : 20 PPCM patients < 35% with SBP >95 < 160 /or DBP < 105 I : PPCM-Std (10) vs PPCM-Br (10) O : composite endpoint of death, NYHA Class 3 /4, LVEF <35% at 6months M : prospective randomized open-label clinical trial, PPCM-Std: Enalapril, carvedilol, furosemide, warfarin PPCM-Br: Std + 2.5mg BID X 2wks, 2.5mg OD X 6wks
Peripartum CardiomyopathyPeripartum Cardiomyopathy: Bromocriptine StudyBromocriptine Study
25) Sliwa K et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof of concept pilot study. Circulation. 2010; 121: 1465-1473
23
- P : 20 PPCM patients < 35% with SBP>95 < 160 /or DBP<105 I : PPCM-Std (10) vs PPCM-Br (10) O : composite endpoint of death, NYHA class 3 /4, LVEF <35% at 6months M : prospective randomized open-label clinical trial, PPCM-Std: Enalapril, carvedilol, furosemide, warfarin PPC-Br: Std + 2.5mg BID X 2Wks, 2.5 OD X 6Wks- Results: > Similar in baseline characteristics: BP, Labs, LVED/LVESD, LVEF > Changes in NT-proBNP, 16kDa prolactin & cathepsin D = NS > Changes in S or D BP and LVEDD or LVESD = NS
Peripartum CardiomyopathyPeripartum Cardiomyopathy: Bromocriptine StudyBromocriptine Study
25) Sliwa K et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof of concept pilot study. Circulation. 2010; 121: 1465-1473
24
Peripartum CardiomyopathyPeripartum Cardiomyopathy: Bromocriptine StudyBromocriptine Study
25) Sliwa K et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof of concept pilot study. Circulation. 2010; 121: 1465-1473
25
- Results: 25
> Recovery of EF: 31% better for PPCM-BR (2758%); PPCM-Std (27%36%), p=0.012
> Primary Outcome: PPCM-Br patients better outcome, P=0.006- Conclusion: > Addition of bromocriptine to standard HF therapy appears to improve LVEF, functional class and survival in women with severe acute PPCM w/ no obvious detriment to their children at 6 mos of study. > beneficial effects said to result from eliminating detrimental effects of 16 kDa prolactin form > “off target” effects on hemodynamics26, 27
increase in BP, vascular resistance, plasma norepinephrine levels increase SVI, decrease LV filling pressure > Caution: reports of stroke, seizure, coronary vartery thrombosis and coronary vasospasm in normal women
Peripartum CardiomyopathyPeripartum Cardiomyopathy: Bromocriptine StudyBromocriptine Study
25) Sliwa K et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof of concept pilot study. Circulation. 2010; 121: 1465-147326) Francis GS, et al. The effects of bromocriptine in patients with congestion heart failure. Am Heart J. 1983; 106 (pt1): 100-10627) Goldberg LI, et al. The role of dopamine receptors in the treatment of congestive heart failure. J Cardiovasc Pharmacol. 1989; 14 (suppl 5): s19-s27
26
Prognosis:- Treatment duration: continued until recovery of LV function, 6-12 months or lifetime- Usually return to normal heart size within 6 months- 30-50% recover baseline LV function within 6 months16, 28
- Prognosis is positively related to recovery of LV function16
- failure of LV size to return to N is associated w/ inc M & M5
28) Abboud J, et al. Peripartum cardiomyopathy: a comprehensive review. Int J Cardiol. 2007; 118 (3): 295-303
29) Felker GM, et al. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000; 342: 1077-1084
5) Pearson G et al. National Heart, Lung and Blood Institute and Office of Rare Diseases (National Institute of Health) Workshop Recommendations and review. JAMA. 2000; 283 (9): 1183-1188
16) Ntusi NB, et al. Aetiology and risk factors of peripartum cardiomyopathy: a systematic review. Int J Cardiol. 2009; 131 (2): 168-179
4) Fett JD et al. Five year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc 2005; 80 (12): 1602-1606
27
Prognosis:- Predictors for normalization:30, 31
a) LVEDD < 55mm b) LVEF > 27%
- Predictors for persistent LV dysfunction:30, 31, 32
a) Trop T (measured 2 wks after onset) = inversely correlated with LV function at 6 months: > 0.04ng/ml (Sn=55%, Sp=91%) b) FS < 20% c) LVEDD > 56 – 60 mm
31) Duran N, et al. Predictors of prognosis in patients with peripartum cardiomyopathy. Int J Gynaecol Obstet 2008; 101: 137-14032) Hu CL, etal. Troponin T measurement can predict persistent left ventricular dysfunction in peripartum cardiomyopathy. Heart 2007; 93: 488-490
12) Sliwa K et al. Peripartum Cardiomyopathy: analysis of clinical outcome, LV function, plasma levels of cytokines and Fas/Apo-1. J Am Coll Cardiol. 2000; 35 (3): 701-70530) Dorbala S et al. Risk stratification of women with peripatum cardiomyopathy at initial presentation: a dobutamine stress echocardiography study. J Am Soc Echocardiogr 2005; 18: 45-48
28
Prognosis:- Counselling: (recommendation for subsequent pregnancy) > do DBS to measure maximal inotropic contractile reserve correlated with subsequent recovery of LV function Recommendations:30
a) if LV function recovered fully, subsequent pregnancy not CI but
should be warned of recurrence b) if partial LV function recovered, perform the DBS:30
- N response (appropriate augmentation) pregnancy not CI but warned - AbN response, risk is moderate, subsequent pregnancy CI c) if LV function not recovered, subsequent pregnancy CI
30) Dorbala S et al. Risk stratification of women with peripatum cardiomyopathy at initial presentation: a dobutamine stress echocardiography study. J Am Soc Echocardiogr 2005; 18: 45-48
29
- Peripartaum cardiomyopathy is distinctly defined albeit a diagnosis mostly by exclusion with its criteria
- Plausible etiologic mechanisms make it difficult for targeted treatment regimen
- Treatment is based on HF guidelines, w/ the goal of improving hemodynamic status focused on reducing preload / afterload and increasing cardiac inotropy with careful attention to fetal safety, drug metabolism and excretion.