JACC. CardioOncology (Dec 2019)

Increased Cancer Prevalence in Peripartum Cardiomyopathy

  • Tobias J. Pfeffer, MD,
  • Stella Schlothauer, MS,
  • Stefan Pietzsch, PhD,
  • Maria Schaufelberger, MD,
  • Bernd Auber, MD,
  • Melanie Ricke-Hoch, PhD,
  • Manuel List, MS,
  • Dominik Berliner, MD,
  • Valeska Abou Moulig, MD,
  • Tobias König, MD,
  • Zolt Arany, MD, PhD,
  • Karen Sliwa, MD,
  • Johann Bauersachs, MD,
  • Denise Hilfiker-Kleiner, PhD

Journal volume & issue
Vol. 1, no. 2
pp. 196 – 205

Abstract

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Objectives: This study was designed to analyze the prevalence and potential genetic basis of cancer and heart failure in peripartum cardiomyopathy (PPCM). Background: PPCM manifests as heart failure late in pregnancy or postpartum in women without previous heart disease. Methods: Clinical history and cancer prevalence were evaluated in a cohort of 236 PPCM patients from Germany and Sweden. Exome sequencing assessed variants in 133 genes associated with cancer predisposition syndromes (CPS) and in 115 genes associated with dilated/hypertrophic cardiomyopathy (DCM/HCM) in 14 PPCM patients with a history of cancer, and in 6 PPCM patients without a history of cancer. Results: The prevalence of cancer was 16-fold higher (8.9%, 21 of 236 patients) in PPCM patients compared to age-matched women (German cancer registry, Robert-Koch-Institute: 0.59%; p < 0.001). Cancer before PPCM occurred in 12 of 21 patients of whom 11 obtained cardiotoxic cancer therapies. Of those, 17% fully recovered cardiac function by 7 ± 2 months of follow-up compared to 55% of PPCM patients without cancer (p = 0.015). Cancer occurred after PPCM in 10 of 21 patients; 80% had left ventricular ejection fraction of ≥50% after cancer therapy. Whole-exome sequencing in 14 PPCM patients with cancer revealed that 43% (6 of 14 patients) carried likely pathogenic (Class IV) or pathogenic (Class V) gene variants associated with DCM/HCM in CPT2, DSP, MYH7, TTN, and/or with CPS in ATM, ERCC5, NBN, RECQL4, and SLX4. All CPS variants affected DNA damage response genes. Conclusions: Cardiotoxic cancer therapy before PPCM is associated with delayed full recovery. The high cancer prevalence in PPCM is linked to likely pathogenic/pathogenic gene variants associated with DCM/HCM and/or CPS/DNA damage response–related cancer risk. This may warrant genetic testing and screening for heart failure in pregnant women with a cancer history and screening for cancer in PPCM patients.

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