Aim Population‐based European studies of peripartum cardiomyopathy (PPCM) are few. We aimed to estimate the nationwide incidence and outcome of PPCM in Denmark during 2005–2014. Methods and results The Danish National Birth Register and the Danish National Patient Register were linked and searched for cardiomyopathy and heart failure ICD‐10 diagnoses in a period of nine months before to 12 months after a delivery from 1 January 2005 through 31 December 2014. Diagnoses were validated and additional data were extracted from patient charts. A total of 61 women met the inclusion criteria equalling 1 in 10 149 deliveries. The majority recovered left ventricular systolic function within one year, but 14.8% suffered a major adverse event with 3.3% mortality, 8.2% mechanical circulatory support requirement and/or heart transplantation and 4.9% persistent severe heart failure. Half of the women had a concomitant hypertensive disorder of pregnancy, and this subgroup had a milder course of the disease. Baseline left ventricular ejection fraction (LVEF) was the only significant predictor of LVEF 10–14 months after diagnosis, and cabergoline therapy to inhibit lactation predicted the dichotomous outcome of complete recovery (LVEF ≥55%). Conclusion The first validated, population‐based European estimate of PPCM incidence is 1 in 10 149 deliveries, which places Denmark between American and Japanese estimates. Clinical outcome in the cohort was similar to those reported in recent cohorts. Women with concomitant hypertensive disorder of pregnancy had a milder course of PPCM. Baseline LVEF predicted LVEF 10–14 months after diagnosis and cabergoline predicted complete recovery.

Background: Peripartum cardiomyopathy (PPCM) occurs in approximately 1:2000 deliveries in the US and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN , and evaluated for burden of truncating and missense variants. The impact of TTNtvs on severity of clinical presentation, and on clinical outcomes, was evaluated. Results: 469 women met inclusion criteria. 10.4% of women with PPCM bore TTNtvs (Odds ration [OR]=9.4 compared with 1.2% in reference population; Bonferroni-corrected P [P*] =1.2x10 -46 ). We additionally identified overrepresentation of truncating variants in FLNC (OR=24.8, P*=7.0x10 -8 ), DSP (OR=14.9, P*=1.0x10-8), and BAG3 (OR=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in non-ischemic dilated cardiomyopathy (DCM). Women with TTNtvs had lower left ventricular ejection fraction (LVEF) on presentation than did women without TTNtvs (23.5% vs 29%, P=2.5x10 -4 ), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM, and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and DCM, suggesting that gene-specific therapeutic approaches being developed for DCM may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in DCM. Finally, the clarification of genotype/phenotype associations has important implications for genetic counseling.