Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Alice M. Jackson¹, Mark C. Petrie^1,2, Alexandra Frogoudaki³, Cecile Laroche⁴, Finn Gustafsson⁵, Bassem Ibrahim⁶, Alexandre Mebazaa⁷, Mark R. Johnson⁸, Petar M. Seferovic⁹, Vera Regitz-Zagrosek¹⁰, Amam Mbakwem¹¹, Michael Bohm¹², Hawani S. Prameswari¹³, Doaa A. Fouad¹⁴, Sorel Goland¹⁵, Albertino Damasceno¹⁶, Kamilu Karaye¹⁷, Hasan A. Farhan¹⁸, Righab Hamdan¹⁹, Aldo P. Maggioni^4,20, Karen Sliwa²¹, Johann Bauersachs²², and Peter van der Meer^2,3*, on behalf of the PPCM Investigators Group

 

Take Home Points:

• Women with PPCM-PE presented with more severe symptoms and signs of heart failure, compared to PPCM-noHTN despite having better baseline cardiac function, occurring later in the pregnancy and concentrated around the time of delivery
• PPCM-PE showed greater LVEF recovery
• Neonatal death was most common in PCM-PE
• PPCM-PE was associated with greater rates of adverse neonatal outcome

 

 

Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch:

The relationship between hypertensive disorders and peri-partum cardiomyopathy (PPCM) is poorly understood. The prevalence of hypertensive disorders in patients with PPCM is ±20-25% for pre-eclampsia and 40% for hypertension. Both conditions are known to result in endothelial dysfunction, suggesting overlap in pathophysiological mechanisms. Potential explanations include: both conditions exist on a shared disease spectrum, pregnancy-induced hypertension is a risk factor for PPCM, or that they are entirely separate disease processes. The authors investigated the maternal and neonatal outcomes in women with PPCM with and without hypertension within the largest prospective cohort of women with PPCM, the EORP (ESC EURO-observational Research Programme) Registry.

The EORP registry enrolled 752 women from 51 countries within 6 months of their diagnosis of PPCM (peripartum state, heart failure, LVEF < 45%, no other causes of heart failure). Pregnancy-induced hypertension and pre-eclampsia was reported by the attending clinician. Patients with PPCM were divided into 3 groups:

1. No hypertension (PPCM-noHTN)
2. Pregnancy-induced hypertension without pre-eclampsia (PPCM-HTN)
3. Pre-eclampsia (PPCM-PE)

The following outcomes were reported at 6 months:

• Death (heart failure, sudden cardiac death or all cause)
• Heart failure re-hospitalization; all-cause hospitalization
• Thrombo-embolic events – venous and arterial
• Stroke
• Neonatal outcomes: APGAR scores at 1 and 5 minutes, low birth weight, termination, miscarriage, death
• LV function at 6 months
• Composite of LV function and death

Hypertensive status was documented in 97,7% of the total cohort (n=735) with the following split:

1. PPCM-noHTN – 452 (61.5%)
2. PPCM-HTN – 99 (13.5%)
3. PPCM-PE – 184 (25%)

Across the hypertension groups there was no difference in terms of age, parity, diabetes, smoking history, or HIV. Significant other baseline characteristics:

 

	PPCM-noHTN	PPCM-HTN	PPCM-PE
Baseline systolic BP	112.1 mmHg	131.2 mmHg	133.2 mmHg	p <0.001
Symptoms prior to the last month of pregnancy in:	14.2%	17.3%	8%	p =0.001
Family history of DCM	4%	9.1%	0%	p<0.001
Family history of PPCM	1.8%	0%	0%	p=0.08
NYHA III/IV symptoms	65.2%	60%	74.4%	p <0.001
Serum creatinine (μmol/l)	70.0	72.0	79.6	p <0.001
Baseline LVEF	30.7%	32.8%	32.7%	p=0.005

 

 

By 6 months, most PPCM-PE patients were treated with an ACE-inhibitor or ARB, and least frequently commenced on an MRA. All other medication uses across the hypertension groups were similar.

 

Caesarian section was more frequently done in those with PPCM-HTN and PPCM-PE compared to PPCM-noHTN – in both pre- and postpartum diagnoses. Both post-partum haemorrhage and the use of tocolytic therapy was more frequently seen in patients with PPCM-PE compared to the other 2 groups.

 

There was not statistically significant difference in the rates of death at 6 months between the 3 groups (6.5%, 1.2% and 6.9% respectively for PPCM-noHTN, PPCM-HTN, PPCM-PE, p=0.16). Figure 3 below shows that re-hospitalization rates (all-cause and heart failure) as well as thrombo-embolism rates for the 3 groups were also similar (p=0.21)

 

 

LVEF recovery occurred in 41.5% of patients with PPCM-noHTN, in 48.5% of women with PPCM-HTN and in 57.5% of women with PPCM-PE (p=0.01). Compared to women with PPCM-noHTN, LVEF recovery was 1.9 times higher in women with PPCM-PE (unadjusted OR 1.91, 95%CI 1.24-2.94). This correlation of pre-eclampsia nad LV recovery persisted even when adjusting for other variables (baseline LVEF, BMI, region, serum creatinine), adjusted OR 2.08; 95% CI 1.21-1.28).

 

Neonatal outcomes showed the following results:

• Birthweight and APGAR scores were highest in the patients with PPCM-noHTN, and lowest in PPCM-PE
• Neonatal death occurred with increasing frequency in the groups of PPCM-noHTN, PPCM-HTN, PPCM-PE (1.8%, 5.6%, 9.1%, p<0.001)
• Systolic and diastolic BP increases of 10mmHg, were associated with a greater likelihood of adverse neonatal outcome (adjusted OR 1.17, 95% CI 1.05-1.30 for systolic BP and OR 1.23, 95% CI 1.06-1.43 for diastolic BP)