Increased cancer prevalence in peripartum cardiomyopathy

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

Outcome in German and South African peripartum cardiomyopathy cohorts associates with medical therapy and fibrosis markers

Aims This study aims to compare the clinical course of peripartum cardiomyopathy (PPCM) cohorts from Germany (G‐PPCM) and South Africa (SA‐PPCM) with fibrosis‐related markers to get insights into novel pathomechanisms of PPCM. Methods and results G‐PPCM (n = 79) and SA‐PPCM (n = 72) patients and healthy pregnancy‐matched women from Germany (n = 56) and South Africa (n = 40) were enrolled. Circulating levels of procollagen type‐I (PINP) and type‐III (PIIINP) N‐terminal propeptides, soluble ST2, galectin‐3, and full‐length and cleaved osteopontin (OPN) were measured at diagnosis (baseline) and 6 months of follow‐up. Both cohorts received standard heart failure therapy while anticoagulation therapy was applied in 100% of G‐PPCM but only in 7% of SA‐PPCM patients. In G‐PPCM patients, baseline left ventricular ejection fraction (LVEF) was lower, and outcome was better (baseline LVEF, 24 ± 8%, full recovery: 52%, mortality: 0%) compared with SA‐PPCM patients (baseline LVEF: 30 ± 9%, full recovery: 32%, mortality: 11%; P < 0.05). At baseline, PINP/PIIINP ratio was lower in SA‐PPCM and higher in G‐PPCM compared with respective controls, whereas total OPN was elevated in both collectives. Cleaved OPN, which increases PIIINP levels, is generated by thrombin and was reduced in patients receiving anticoagulation therapy. High baseline galectin‐3, soluble ST2, and OPN levels were associated with poor outcome in all PPCM patients. Conclusions SA‐PPCM patients displayed a more profibrotic biomarker profile, which was associated with a less favourable outcome despite better cardiac function at baseline, compared with G‐PPCM patients. Use of bromocriptine and anticoagulation therapy in G‐PPCM may counteract fibrosis and may in part be responsible for their better outcome

Clinical characteristics and long-term outcomes in patients with peripartum cardiomyopathy (PPCM) receiving left ventricular assist devices (LVAD)

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF), presenting with left ventricular (LV) systolic dysfunction either at the end of pregnancy or in the months following delivery. In rare cases PPCM leads to severe impairment of LV function, refractory cardiogenic shock or advanced HF. LV assist devices (LVAD) have been shown to be a feasible treatment option in advanced HF. However, little is known about long-term outcomes and prognosis of PPCM patients undergoing LVAD implantation. METHODS: A retrospective analysis of data from PPCM patients undergoing LVAD implantation in two tertiary centers with respect to long-term outcomes was performed. RESULTS: Twelve patients of median age 30 (18-39) years were included. Eight patients were experiencing cardiogenic shock (INTERMACS 1) at implantation. Seven patients were implanted within one month of their PPCM diagnosis. Median duration of LVAD support was 19 (2-92) months with median follow up of 67 (18-136) months (100% complete). In-hospital and 1-year mortality were 0% and 8.3% respectively. Two patients died on LVAD support, four patients were successfully bridged to transplantation, two patients are still on LVAD, and four were successfully weaned due to sufficient LV recovery (one died after LV function deteriorated again). CONCLUSION: LVAD treatment of decompensated end-stage PPCM is feasible. Early LVAD provision led to hemodynamic stabilization in our cohort and facilitated safe LV recovery in one third of these young female patients

Bromocriptine treatment in patients with peripartum cardiomyopathy and right ventricular dysfunction

BackgroundRight ventricular (RV) dysfunction predicts adverse outcome in peripartum cardiomyopathy (PPCM). We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM. Here, we evaluated for the first time the therapeutic potential of bromocriptine particularly in PPCM patients with RV involvement.MethodsIn this study, 40 patients with PPCM were included, of whom 24 patients had reduced RV ejection fraction (RVEF<45%). We examined the effect of short-term (1W: bromocriptine, 2.5mg, 7days, n=10) compared with long-term bromocriptine treatment (8W: 5mg for 2weeks followed by 2.5mg for another 6weeks, n=14) in addition to guideline-based heart failure therapy in patients with an initial RVEF<45% on the following outcomes: (1) change from baseline ( delta) in RVEF, (2) change from baseline in left ventricular EF (LVEF), and (3) rate of patients with full LV recovery (LVEF50%) and (4) rate of patients with full RV recovery (RVEF55%) at 6-month follow-up as assessed by cardiac magnetic resonance imaging.ResultsReduced RVEF at initial presentation was associated with a lower rate of full cardiac recovery at 6-month follow-up (patients with RV dysfunction: 58% vs. patients with normal RV function: 81%; p=0.027). RVEF increased from 387 to 53 +/- 11% with a delta-RVEF of +15 +/- 12% in the 1W group, and from 35 +/- 9 to 58 +/- 7% with a RVEF of +23 +/- 10% in the 8W group ( RVEF 1W vs 8W: p=0.118). LVEF increased from 25 +/- 8 to 46 +/- 12% with a LVEF of +21 +/- 11% in the 1W group, and from 22 +/- 6 to 49 +/- 10% with a LVEF of +27 +/- 9% in the 8W group ( LVEF 1W vs 8W: p=0.211). Full LV recovery was present in 50% of the 1W group and in 64% of the 8W group (p=0.678). Full RV recovery was observed in 40% of the 1W group and in 79% of the 8W group (p=0.092).ConclusionsDespite overall worse outcome in patients with RV dysfunction at baseline, bromocriptine treatment in PPCM patients with RV involvement was associated with a high rate of full RV and LV recovery, although no significant differences were observed between the short-term and long-term bromocriptine treatment regime. These findings suggest that bromocriptine in addition to standard heart failure therapy may be also effective in PPCM patients with biventricular impairment