Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy
Tóm tắt
Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.
Tài liệu tham khảo
Anderssohn M, Rosenberg M, Schwedhelm E, Zugck C, Lutz M, Luneburg N, Frey N, Boger RH (2012) The l-Arginine-asymmetric dimethylarginine ratio is an independent predictor of mortality in dilated cardiomyopathy. J Card Fail 18:904–911. doi:10.1016/j.cardfail.2012.10.011
Blauwet LA, Cooper LT (2011) Diagnosis and management of peripartum cardiomyopathy. Heart 97:1970–1981. doi:10.1136/heartjnl-2011-300349
Elkayam U (2011) Clinical characteristics of peripartum cardiomyopathy in the United States: diagnosis, prognosis, and management. J Am Coll Cardiol 58:659–670. doi:10.1016/j.jacc.2011.03.047
Fett JD (2002) Peripartum cardiomyopathy. Insights from Haiti regarding a disease of unknown etiology. Minn Med 85:46–48
Forster O, Hilfiker-Kleiner D, Ansari AA, Sundstrom JB, Libhaber E, Tshani W, Becker A, Yip A, Klein G, Sliwa K (2008) Reversal of IFN-gamma, oxLDL and prolactin serum levels correlate with clinical improvement in patients with peripartum cardiomyopathy. Eur J Heart Fail 10:861–868. doi:10.1016/j.ejheart.2008.07.005
Goland S, Bitar F, Modi K, Safirstein J, Ro A, Mirocha J, Khatri N, Elkayam U (2011) Evaluation of the clinical relevance of baseline left ventricular ejection fraction as a predictor of recovery or persistence of severe dysfunction in women in the United States with peripartum cardiomyopathy. J Card Fail 17:426–430. doi:10.1016/j.cardfail.2011.01.007
Goland S, Modi K, Bitar F, Janmohamed M, Mirocha JM, Czer LS, Illum S, Hatamizadeh P, Elkayam U (2009) Clinical profile and predictors of complications in peripartum cardiomyopathy. J Card Fail 15:645–650. doi:10.1016/j.cardfail.2009.03.008
Haghikia A, Missol-Kolka E, Tsikas D, Venturini L, Brundiers S, Castoldi M, Muckenthaler MU, Eder M, Stapel B, Thum T, Petrasch-Parwez E, Drexler H, Hilfiker-Kleiner D, Scherr M (2011) Signal transducer and activator of transcription 3-mediated regulation of miR-199a-5p links cardiomyocyte and endothelial cell function in the heart: a key role for ubiquitin-conjugating enzymes. Eur Heart J 32:1287–1297. doi:10.1093/eurheartj/ehq369
Halkein J, Tabruyn SP, Ricke-Hoch M, Haghikia A, Nguyen NQ, Scherr M, Castermans K, Malvaux L, Lambert V, Thiry M, Sliwa K, Noel A, Martial JA, Hilfiker-Kleiner D, Struman I (2013) MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Invest 123:2143–2154. doi:10.1172/jci64365
Hilfiker-Kleiner D, Kaminski K, Podewski E, Bonda T, Schaefer A, Sliwa K, Forster O, Quint A, Landmesser U, Doerries C, Luchtefeld M, Poli V, Schneider MD, Balligand JL, Desjardins F, Ansari A, Struman I, Nguyen NQ, Zschemisch NH, Klein G, Heusch G, Schulz R, Hilfiker A, Drexler H (2007) A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 128:589–600. doi:10.1016/j.cell.2006.12.036
Hilfiker-Kleiner D, Meyer GP, Schieffer E, Goldmann B, Podewski E, Struman I, Fischer P, Drexler H (2007) Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine. J Am Coll Cardiol 50:2354–2355. doi:10.1016/j.jacc.2007.10.006
Kamiya CA, Kitakaze M, Ishibashi-Ueda H, Nakatani S, Murohara T, Tomoike H, Ikeda T (2011) Different characteristics of peripartum cardiomyopathy between patients complicated with and without hypertensive disorders. Results from the Japanese Nationwide survey of peripartum cardiomyopathy. Circ J 75:1975–1981. (pii: JST.JSTAGE/circj/CJ-10-1214)
McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Task Force for the D, Treatment of A, Chronic Heart Failure of the European Society of C, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P, Guidelines ESCCfP (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 14:803–869. doi:10.1093/eurjhf/hfs105
Morales A, Painter T, Li R, Siegfried JD, Li D, Norton N, Hershberger RE (2010) Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy. Circulation 121:2176–2182. doi:10.1161/CIRCULATIONAHA.109.931220
Patten IS, Rana S, Shahul S, Rowe GC, Jang C, Liu L, Hacker MR, Rhee JS, Mitchell J, Mahmood F, Hess P, Farrell C, Koulisis N, Khankin EV, Burke SD, Tudorache I, Bauersachs J, del Monte F, Hilfiker-Kleiner D, Karumanchi SA, Arany Z (2012) Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature 485:333–338. doi:10.1038/nature11040
Pearson GD, Veille JC, Rahimtoola S, Hsia J, Oakley CM, Hosenpud JD, Ansari A, Baughman KL (2000) Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA, J Am Med Assoc 283:1183–1188. doi:10.1001/jama.283.9.1183
Ross RM, Baker T (1995) Cardiac enzymes in patients undergoing caesarean section. Can J Anaesth 42:46–50. doi:10.1007/BF03010571
Savvidou MD, Hingorani AD, Tsikas D, Frolich JC, Vallance P, Nicolaides KH (2003) Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 361:1511–1517
Selle T, Renger I, Labidi S, Bultmann I, Hilfiker-Kleiner D (2009) Reviewing peripartum cardiomyopathy: current state of knowledge. Future Cardiol 5:175–189. doi:10.2217/14796678.5.2.175
Sliwa K, Blauwet L, Tibazarwa K, Libhaber E, Smedema JP, Becker A, McMurray J, Yamac H, Labidi S, Struman I, Hilfiker-Kleiner D (2010) Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study. Circulation 121:1465–1473. doi:10.1161/CIRCULATIONAHA.109.901496
Sliwa K, Fett J, Elkayam U (2006) Peripartum cardiomyopathy. Lancet 368:687–693. doi:10.1016/S0140-6736(06)69253-2
Sliwa K, Forster O, Libhaber E, Fett JD, Sundstrom JB, Hilfiker-Kleiner D, Ansari AA (2006) Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients. Eur Heart J 27:441–446. doi:10.1093/eurheartj/ehi481
Sliwa K, Forster O, Tibazarwa K, Libhaber E, Becker A, Yip A, Hilfiker-Kleiner D (2009) Long-term outcome of peripartum cardiomyopathy in a population with high seropositivity for human immunodeficiency virus. Int J Cardiol 147:202–208. doi:10.1016/j.ijcard.2009.08.022
Sliwa K, Hilfiker-Kleiner D, Petrie MC, Mebazaa A, Pieske B, Buchmann E, Regitz-Zagrosek V, Schaufelberger M, Tavazzi L, van Veldhuisen DJ, Watkins H, Shah AJ, Seferovic PM, Elkayam U, Pankuweit S, Papp Z, Mouquet F, McMurray JJ (2010) Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail 12:767–778. doi:10.1093/eurjhf/hfq120
van Spaendonck-Zwarts KY, van Tintelen JP, van Veldhuisen DJ, van der Werf R, Jongbloed JD, Paulus WJ, Dooijes D, van den Berg MP (2010) Peripartum cardiomyopathy as a part of familial dilated cardiomyopathy. Circulation 121:2169–2175
Walenta K, Schwarz V, Schirmer SH, Kindermann I, Friedrich EB, Solomayer EF, Sliwa K, Labidi S, Hilfiker-Kleiner D, Bohm M (2012) Circulating microparticles as indicators of peripartum cardiomyopathy. Eur Heart J 33:1469–1479