PERIPARTUM CARDIOMYOPATHY: A COMPARATIVE ANALYSIS OF TWIN VERSUS SINGLETON GESTATIONAL RISKS: A NARRATIVE REVIEW
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6199Keywords:
Peripartum Cardiomyopathy, Pregnancy, Multiple, Heart Failure, Pre-Eclampsia, Risk Factors, HemodynamicsAbstract
Background. Peripartum cardiomyopathy is an idiopathic left ventricular systolic heart-failure syndrome presenting in late pregnancy or up to five months postpartum, with global incidence ranging from 1 per 1000–4000 births in North America and Europe to 1 per 100–300 in parts of sub-Saharan Africa. Multifetal gestation is a recurring risk factor, though its adjusted magnitude is uncertain.
Aim. To synthesise contemporary evidence on whether multifetal gestation constitutes an independent, mechanistically grounded PPCM risk factor.
Methods. A structured narrative review (January 2000–March 2026) of PubMed/MEDLINE, Scopus, and Web of Science records, supplemented by reference-list and guideline cross-referencing, including peer-reviewed primary studies, systematic or narrative reviews, and meta-analyses on PPCM epidemiology, hemodynamics, molecular biology, therapy, and prognosis in multifetal versus singleton gestations.
Results. A 2024 Finnish record-linkage study identified twin pregnancy as conferring an adjusted odds ratio of 2.74 (95% CI 1.37–5.49, p = 0.005) for peripartum heart failure, comparable to pre-eclampsia (aOR 2.43) (Puhakka et al., 2024). Twin gestation imposes 20% greater cardiac output, 15% greater stroke volume, and 13.5% greater left ventricular mass than singleton pregnancy, with progressive third-trimester loss of long-axis systolic efficiency (Kametas, 2003). A 2025 systematic review confirmed multifetal gestation as a recurrent risk factor across diverse cohorts (Dewi et al., 2025), corroborated by a 2022 global meta-analysis of over 7,000 cases from 41 studies (Hoevelmann et al., 2022).
Conclusions. Multifetal gestation is an independent PPCM risk factor of comparable magnitude to pre-eclampsia, mediated by hemodynamic loading and amplified anti-angiogenic signalling on a genetic substrate (Davis et al., 2020). Incorporation of pregnancy plurality into stratified PPCM risk models is justified by this synthesis (Jackson et al., 2023).
References
Abbas, S. (2024). CASE REPORT: PERIPARTUM CARDIOMYOPATHY, A RARE BUT FATAL CONDITION IN PREGNANCY AND PUERPERIUM. https://doi.org/10.53555/e2f46s45
Adank, M. C., Broere-Brown, Z. A., Gonçalves, R., Ikram, M. K., Jaddoe, V. W. V., Steegers, E. A. P., & Schalekamp–Timmermans, S. (2020). Maternal cardiovascular adaptation to twin pregnancy: a population-based prospective cohort study. BMC Pregnancy and Childbirth, 20(1), 327–327. https://doi.org/10.1186/s12884-020-02994-w
Aimo, A., Morfino, P., Arzilli, C., Vergaro, G., Spini, V., Fabiani, I., Castiglione, V., Rapezzi, C., & Emdin, M. (2024). Disease features and management of cardiomyopathies in women. https://doi.org/10.1007/s10741-024-10386-x
Aryan, L., Medzikovic, L., Umar, S., & Eghbali, M. (2020). Pregnancy-associated cardiac dysfunction and the regulatory role of microRNAs. https://doi.org/10.1186/s13293-020-00292-w
Azibani, F., & Sliwa, K. (2018). Peripartum Cardiomyopathy: an Update. https://doi.org/10.1007/s11897-018-0404-x
Bandyopadhyay, A., Puri, S., Samra, T., & Ashok, V. (2024). Preeclamptic heart failure — perioperative concerns and management: a narrative review. Perioperative Medicine, 13(1), 37–37. https://doi.org/10.1186/s13741-024-00391-x
Bauersachs, J., Arrigo, M., Hilfiker‐Kleiner, D., Veltmann, C., Coats, A. J. S., Crespo‐Leiro, M. G., Boer, R. A. de, Meer, P. van der, Maack, C., Mouquet, F., Petrie, M. C., Piepoli, M., Regitz‐Zagrosek, V., Schaufelberger, M., Seferović, P., Tavazzi, L., Ruschitzka, F., Mebazaa, A., & Sliwa, K. (2016). Current Management of Patients with Severe Acute Peripartum Cardiomyopathy: Practical Guidance from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy. https://doi.org/10.1002/ejhf.586
Bauersachs, J., König, T., Meer, P. van der, Petrie, M. C., Hilfiker‐Kleiner, D., Mbakwem, A., Hamdan, R., Jackson, A. M., Forsyth, P., Boer, R. A. de, Mueller, C., Lyon, A. R., Lund, L. H., Piepoli, M., Heymans, S., Chioncel, O., Anker, S. D., Ponikowski, P., Seferović, P., … Sliwa, K. (2019). Pathophysiology, Diagnosis and Management of Peripartum Cardiomyopathy: A Position Statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy. European Journal of Heart Failure, 21(7), 827–843. https://doi.org/10.1002/ejhf.1493
Bello, N. A., & Arany, Z. (2015). Molecular mechanisms of peripartum cardiomyopathy: A vascular/hormonal hypothesis. https://doi.org/10.1016/j.tcm.2015.01.004
Blauwet, L. A., & Sliwa, K. (2011). Peripartum cardiomyopathy. https://doi.org/10.1258/om.2010.100054
Chakafana, G., Spracklen, T. F., Kamuli, S., Zininga, T., Shonhai, A., Ntusi, N., & Sliwa, K. (2021). Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy. https://doi.org/10.3389/fcvm.2021.633013
Chandna, A. (2025). Management of Peri-partum cardiomyopathy in twin pregnancy. https://doi.org/10.62830/mmj2-01-19c
Chung, E., & Leinwand, L. A. (2014). Pregnancy as a cardiac stress model. https://doi.org/10.1093/cvr/cvu013
Davis, M. B., Arany, Z., McNamara, D. M., Goland, S., & Elkayam, U. (2020). Peripartum Cardiomyopathy. Journal of the American College of Cardiology, 75(2), 207–221. https://doi.org/10.1016/j.jacc.2019.11.014
Dewi, T. I., Muthiah, A., Achmad, C., Wirakusumah, F. F., Anwar, R., Nugrahani, A. D., & Oceandi, D. (2025). Association between multiple pregnancy with peripartum cardiomyopathy: a systematic review and meta-analysis. BMC Cardiovascular Disorders, 25(1), 775–775. https://doi.org/10.1186/s12872-025-05229-y
Fairweather, D., Cooper, L. T., & Blauwet, L. A. (2012). Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy. Current Problems in Cardiology, 38(1), 7–46. https://doi.org/10.1016/j.cpcardiol.2012.07.003
Foglietta, M., D’Antonio, F., Pierdomenico, S. D., Bacigalupi, E., & Pizzicannella, J. (2023). Twin pregnancies and maternal cardiovascular function: literature review and future prospects. https://doi.org/10.36253/ijae-14700
Gerloni, R., & Panuccio, D. (2017). Pregnancy and heart disease: what Internists should know. https://doi.org/10.4081/itjm.2017.815
Ghi, T., Esposti, D. D., Montaguti, E., Rosticci, M., Tancredi, S., Youssef, A., Giovanni, M. V. di, Pilu, G., Borghi, C., & Rizzo, N. (2015). Maternal cardiac evaluation during uncomplicated twin pregnancy with emphasis on the diastolic function. https://doi.org/10.1016/j.ajog.2015.05.003
Haghikia, A., Podewski, E., Berliner, D., Sonnenschein, K., Fischer, D., Angermann, C. E., Böhm, M., Röntgen, P., Bauersachs, J., & Hilfiker‐Kleiner, D. (2015). Rationale and design of a randomized, controlled multicentre clinical trial to evaluate the effect of bromocriptine on left ventricular function in women with peripartum cardiomyopathy. Clinical Research in Cardiology, 104(11), 911–917. https://doi.org/10.1007/s00392-015-0869-5
Haghikia, A., Podewski, E., Libhaber, E., Labidi, S., Fischer, D., Roentgen, P., Tsikas, D., Jordan, J., Lichtinghagen, R., Kaisenberg, C. S. von, Struman, I., Bovy, N., Sliwa, K., Bauersachs, J., & Hilfiker‐Kleiner, D. (2013). Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy. https://doi.org/10.1007/s00395-013-0366-9
Halkein, J., Tabruyn, S. P., Ricke‐Hoch, M., Haghikia, A., Nguyen, N.-Q.-N., Scherr, M., Castermans, K., Malvaux, L., Lambert, V., Thiry, M., Sliwa, K., Noël, A., Martial, J., Hilfiker‐Kleiner, D., & Struman, I. (2013). MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. Journal of Clinical Investigation, 123(5), 2143–2154. https://doi.org/10.1172/jci64365
Hilfiker‐Kleiner, D., Haghikia, A., Nonhoff, J., & Bauersachs, J. (2015). Peripartum cardiomyopathy: current management and future perspectives. European Heart Journal, 36(18), 1090–1097. https://doi.org/10.1093/eurheartj/ehv009
Hod, T., Cerdeira, A. S., & Karumanchi, S. A. (2015). Molecular Mechanisms of Preeclampsia. https://doi.org/10.1101/cshperspect.a023473
Hoevelmann, J., Engel, M. E., Muller, E., Hohlfeld, A., Böhm, M., Sliwa, K., & Viljoen, C. (2022). A global perspective on the management and outcomes of peripartum cardiomyopathy: a systematic review and meta‐analysis. https://doi.org/10.1002/ejhf.2603
Honigberg, M. C., & Givertz, M. M. (2019). Peripartum cardiomyopathy. https://doi.org/10.1136/bmj.k5287
Jackson, A. M., Dalzell, J. R., Walker, N. L., Coats, C., Jhund, P. S., & Petrie, M. C. (2017). Peripartum cardiomyopathy: diagnosis and management. https://doi.org/10.1136/heartjnl-2016-310599
Jackson, A. M., Macartney, M., Brooksbank, K., Brown, C., Dawson, D., Francis, M., Japp, A. G., Lennie, V., Leslie, S. J., Martin, T. N., Neary, P., Venkatasubramanian, S., Vickers, D., Weir, R. A. P., McMurray, J. J. V., Jhund, P. S., & Petrie, M. C. (2023). A 20-year population study of peripartum cardiomyopathy. European Heart Journal, 44(48), 5128–5141. https://doi.org/10.1093/eurheartj/ehad626
Kametas, N. A. (2003). Maternal cardiac function in twin pregnancy. Obstetrics and Gynecology, 102(4), 806–815. https://doi.org/10.1016/s0029-7844(03)00807-x
Kametas, N. A., McAuliffe, F. M., Krampl, E., Chambers, J. B., & Nicolaides, K. H. (2003). Maternal Cardiac Function in Twin Pregnancy. https://doi.org/10.1097/00006250-200310000-00024
Kim, M. J., & Shin, M. (2017). Practical management of peripartum cardiomyopathy. https://doi.org/10.3904/kjim.2016.360
Kryczka, K., Demkow, M., & Dzielińska, Z. (2024). Biomarkers in Peripartum Cardiomyopathy—What We Know and What Is Still to Be Found. https://doi.org/10.3390/biom14010103
Lueg, J., Schulze, D., Wainstejn, N., Beblo, A., Chiba, T., Tscholl, V., Hindricks, G., & Haverkamp, W. (2025). Efficacy of bromocriptine for the treatment of peripartum cardiomyopathy: an updated meta-analysis. European Heart Journal, 46. https://doi.org/10.1093/eurheartj/ehaf784.4163
Merzouk, F. Z., Oualim, S., & Sabry, M. (2021). Peripartum Cardiomyopathy: The Hidden Enemy. https://doi.org/10.5772/intechopen.97610
Novitalia, B., & Hindariati, E. (2022). Pregnancy-Associated Cardiomyopathy (PACM) in a Preeclamptic Woman with Twin Pregnancy: A Case Report. https://doi.org/10.33678/cor.2021.138
Palmentieri, A., Battaglia, C., D’Alconzo, D., Anastasia, L., Bardi, L., Bifulco, G., Calanducci, M., Carotenuto, M., Cavoretto, P. I., Carusone, F., Lorenzo, E. D., Santo, M., Sardo, A. D. S., Ilardi, F., Ioele, D., Lanni, F., Licciardi, M., Loffredo, F., Manzo, R., … Perrino, C. (2025). Aims and Rationale of a National Registry Integrating Clinical, Echocardiographic, and Multi-Omics Profiling to Promote Precision Medicine in Peripartum Cardiomyopathy. https://doi.org/10.3390/biomedicines13082026
Pellegrino, A., Toncelli, L., Pasquini, L., Mecacci, F., Pedrizzetti, G., & Modesti, P. A. (2023). Enhancement of left ventricular compliance in twin pregnancy. https://doi.org/10.1093/eurjpc/zwad125.300
Peretto, G., Micaglio, E., Ciconte, G., Maia, M., Luzzi, M., Cariello, M., Bonfanti, A. G. R., Lazzeroni, D., Anastasia, L., Cavoretto, P. I., Chieffo, A., Bella, P. D., & Pappone, C. (2024). The “arrhythmic” presentation of peripartum cardiomyopathy: case series and critical review of the literature. https://doi.org/10.3389/fcvm.2024.1362692
Polsinelli, V. B., Hanley‐Yanez, K., McTiernan, C. F., Modi, K., Haythe, J., Skopicki, H. A., Elkayam, U., Cooper, L. T., Fett, J. D., & McNamara, D. M. (2024). Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC. PubMed Central, 49, 100489–100489. https://doi.org/10.1016/j.ahjo.2024.100489
Pretorius, E., Sai, S., Barnet, A., Kodogo, V., Sliwa, K., Chakafana, G., & Zininga, T. (2025). Advances in biomarker discovery for peripartum cardiomyopathy: current status and future directions. Expert Review of Cardiovascular Therapy, 23(12), 903–913. https://doi.org/10.1080/14779072.2025.2591796
Puhakka, A. M., Macharey, G., Ziller, V., Gissler, M., Tekay, A., Keil, C., & Hilfiker‐Kleiner, D. (2024). Peripartum Heart Failure in Finland: A Population-Based Record Linkage Study. https://doi.org/10.1002/ehf2.14996
Raddino, R., Bonadei, I., Teli, M., Chieppa, F., Caretta, G., Robba, D., Zanini, G., Vizzardi, E., & Dei, L. (2016). Peripartum Cardiomyopathy. https://doi.org/10.4081/monaldi.2008.431
Regitz‐Zagrosek, V. (2018). Unsettled Issues and Future Directions for Research on Cardiovascular Diseases in Women. https://doi.org/10.4070/kcj.2018.0249
Ricci, F., Innocentiis, C. D., Verrengia, E., Ceriello, L., Mantini, C., Pietrangelo, C., Irsuti, F., Gabriele, S., D‘Alleva, A., Khanji, M. Y., Aung, N., Renda, G., Cameli, M., Petersen, S. E., Cesare, E. D., & Gallina, S. (2020). The Role of Multimodality Cardiovascular Imaging in Peripartum Cardiomyopathy. Frontiers in Cardiovascular Medicine, 7, 4–4. https://doi.org/10.3389/fcvm.2020.00004
Ricke‐Hoch, M., Pfeffer, T. J., & Hilfiker‐Kleiner, D. (2019). Peripartum cardiomyopathy: basic mechanisms and hope for new therapies. https://doi.org/10.1093/cvr/cvz252
Shmueli, H., Razi, T., Elkayam, U., Zahger, D., Shotan, A., & Arbel, R. (2025). Sociodemographic, cardiovascular and pregnancy associated risk factors to develop peri-partum cardiomyopathy. https://doi.org/10.1093/eurheartj/ehaf784.4175
Shmueli, H., Razi, T., Shental, T. B., Cohen, Y., Shotan, A., Zahger, D., Arbel, R., Battat, T. L., Yaniv-Salem, S., Elkayam, U., & Yamin, D. (2026). Risk Factors and Risk Score (NOAM score) for Peripartum Cardiomyopathy. medRxiv. https://doi.org/10.64898/2026.02.05.26345708
Sigauke, F. R., Ntsinjana, H., & Tsabedze, N. (2024). Peripartum cardiomyopathy: a comprehensive and contemporary review. Heart Failure Reviews, 29(6), 1261–1278. https://doi.org/10.1007/s10741-024-10435-5
Touyz, R. M., & Herrmann, J. (2018). Cardiotoxicity with vascular endothelial growth factor inhibitor therapy. https://doi.org/10.1038/s41698-018-0056-z
Ullmo, J., Cruz‐Lemini, M., Sánchez‐Garcia, O., Real, L. B., Fernández‐Llama, P., Calero, F., Domínguez-Gallardo, C., Garrido‐Giménez, C., Trilla, C., Carreras-Costa, F., Sionís, A., Móra, J., García‐Osuna, Á., Ordóñez‐Llanos, J., & Llurba, E. (2021). Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol. https://doi.org/10.1186/s12884-021-04263-w
Umazume, T., Yamada, T., Furuta, I., Iwano, H., Morikawa, M., Watari, H., & Minakami, H. (2020a). Morphofunctional Cardiac Changes in Singleton and Twin Pregnancies. https://doi.org/10.21203/rs.3.rs-61689/v1
Umazume, T., Yamada, T., Furuta, I., Iwano, H., Morikawa, M., Watari, H., & Minakami, H. (2020b). Morphofunctional Cardiac Changes in Singleton and Twin Pregnancies: A Longitudinal Cohort Study. In Research Square. https://doi.org/10.21203/rs.3.rs-61689/v2
Umazume, T., Yamada, T., Furuta, I., Iwano, H., Morikawa, M., Watari, H., & Minakami, H. (2020c). Morphofunctional cardiac changes in singleton and twin pregnancies: a longitudinal cohort study. https://doi.org/10.1186/s12884-020-03452-3
WALLACE, D. S., Qiu, Y., & Angelidis, I. (2026). Left ventricular cardiomyopathies in pregnancy: clinical challenges, diagnosis, and management. https://doi.org/10.1097/aco.0000000000001633
Warkus, E., Glaze, D., Castro, M., Dowd, A., Drafahl, B., & Hill, W. C. O. (2022). Loving Mothers’ Hearts: Screening for Undiagnosed Cardiomyopathy in Peripartum Women [A229]. Obstetrics and Gynecology, 139(1). https://doi.org/10.1097/01.aog.0000826192.14452.2f
Wolfe, D., Liu, C., Alboucai, J., Karten, A., Mushi, J., Yellin, S., Berkowitz, J., Vega, S., Felix, N., Liaqat, W., Kankaria, R., Vorawandthanachai, T., & Bortnick, A. E. (2022). Maternal Outcomes in Women with Peripartum Cardiomyopathy versus Age and Race-Matched Peers in an Urban US Community. https://doi.org/10.3390/jcdd9080250
Zekert, H. F., Biermann, A.-L., Dütemeyer, V., Meier, N., Radomsky, L., Hillemanns, P., Kaisenberg, C. von, & Brodowski, L. (2025). Longitudinal maternal hemodynamics from late pregnancy to postpartum in uncomplicated twin pregnancies—A glimpse into long‐term cardiovascular risk? https://doi.org/10.1111/aogs.70120
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