Author + information
- Tobias J. Pfeffer, MDa,∗,
- Stella Schlothauer, MSa,∗,
- Stefan Pietzsch, PhDa,
- Maria Schaufelberger, MDb,
- Bernd Auber, MDc,
- Melanie Ricke-Hoch, PhDa,
- Manuel List, MSa,
- Dominik Berliner, MDa,
- Valeska Abou Moulig, MDa,
- Tobias König, MDa,
- Zolt Arany, MD, PhDd,
- Karen Sliwa, MDe,
- Johann Bauersachs, MDa and
- Denise Hilfiker-Kleiner, PhDa,∗ (, )@pfeffer_tj
- aDepartment of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
- bDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- cDepartment of Human Genetics, Hannover Medical School, Hannover, Germany
- dPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- eHatter Institute for Cardiovascular Research in Africa, University of Cape Town, Cape Town, South Africa
- ↵∗Address for correspondence:
Dr. Hilfiker-Kleiner, Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
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.
↵∗ Drs. Pfeffer and Schlothauer contributed equally to this paper.
The Deutsche Forschungsgesellschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), and the DGK-Oskar-Lapp grant supported this study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Anju Nohria, MD, served as Guest Editor-in-Chief and Dr. Uri Elkayam, MD, served as Guest Editor for this paper.
- Received June 14, 2019.
- Revision received August 23, 2019.
- Accepted September 9, 2019.
- 2019 The Authors