Cardio Obstetrics

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry Alice M. Jackson1, Mark C. Petrie1,2, 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. Maggioni4,20, Karen Sliwa21, Johann Bauersachs22, and Peter van der Meer2,3*, 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: No hypertension (PPCM-noHTN) Pregnancy-induced hypertension without pre-eclampsia (PPCM-HTN) 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: PPCM-noHTN – 452 (61.5%) PPCM-HTN – 99 (13.5%) 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-noHTNPPCM-HTNPPCM-PEBaseline systolic BP112.1 mmHg131.2 mmHg133.2 mmHgp <0.001Symptoms prior to the last month of pregnancy in: 14.2%17.3%8%p =0.001Family history of DCM4%9.1%0%p<0.001Family history of PPCM1.8%0%0%p=0.08NYHA III/IV symptoms65.2%60%74.4%p <0.001Serum creatinine (μmol/l)70.072.079.6p <0.001Baseline LVEF30.7%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)   

Heart rate as an early predictor of severe cardiomyopathy and increased mortality in peripartum cardiomyopathy Ryan Cooney MD1 | John R. Scott MPH2 | Madeline Mahowald MD3 | Elizabeth Langen MD4 | Garima Sharma MD5 | David P. Kao MD6 | Melinda B. Davis MD7   Take Home Points Early detection of peripartum cardiomyopathy (PPCM) is desirable to optimise intra/post partum care and to plan for safe delivery. Heart rate is a risk indicator of morbidity and mortality in patients known to have chronic heart failure. This retrospective analysis sought to assess the relationship between heart rate and outcomes in women with PPCM. 82 patients met inclusion criteria. Mean LVEF at the point of diagnosis of PPCM was 26 +/- 11.1% Sinus tachycardia (HR >100) was present in 61% of patients (n=50) at the time of diagnosis. Heart rate predicted lower LVEF (F=30.00, p<0.0001). In an age adjusted logistic regression model, heart rate at diagnosis was associated with a 5x higher risk of mortality when HR at diagnosis was >110 per minute (adjusted OR 5.35, CI 1.23-23.28, p=0.025).Sinus tachycardia in the peripartum period is associated with worse LVEf and so should be considered a ‘red flag’ for potential PPCM.This reaffirms that pregnant women with a tachycardia should be thoroughly assessed for usual reversible causes but if none are found, assessment of LV function should be considered. Resting heart rate is a risk indicator of morbidity and mortality in patients with a variety of cardiovascular conditions. Put very simply, a climbing heart rate, in the absence of other reversible causes e.g. anaemia, infection, thyrotoxicosis, pain, anxiety state etc. suggests that there may be cardiac dysfunction – resting heart rate increases to maintain adequate cardiac output. Heart rate is a very simple yet sensitive indicator of something amiss. This was a retrospective analysis of patients living in the Michigan region whom were diagnosed with PPCM over almost a two decade period (1998-2016) (Figure 1). Heart rate (HR) at the time of diagnosis was determined from the resting ECG rate or by heart rate recorded on initial examination. Naturally, this may introduce error since each patient in the study will not have HR assessed in a similar fashion as per protocol i.e. a set period of rest prior to recording heart rate. Sinus tacycardia was defined as a HR >100 per minute. LVEf measurements were taken at the time of PPCM diagnosis, at 6 months, then at 12 months afterwards. Baseline characteristics of the total cohort and those with a resting heart rate at diagnosis of > 100; >110; >120 per minute are shown in Table 1.   Figure 1. Flowchart of study sample inclusion and exclusion criteria       Results 82 patients were included in the analysis and over 90% of women were diagnosed with PPCM post partum. A sizable number of women (41%) had their pregnancy complicated by hypertension or pre-eclampsia. At the time of PPCM diagnosis, 50 patients (61%) had a sinus tachycardia. Higher heart rates were associated with lower LVEf (Table 2).     Most women in this cohort (n=60) when initially diagnosed with PPCM, had severe LV dysfunction (LVEf <35%), of whom n=40 had an LVEf <25%. It is unclear from the data what proportion had bi-ventricular impairment or co-incident valvar regurgitation i.e. functional MR. Of note, almost all women included in this cohort were prescribed a loop diuretic (n=80) reflective of their heart failure symptomatic status. Most patients were treated according to guideline based medical therapy (beta blocker and ACE-I) with over a third prescribed spironolactone (n=32).   75% of patients had a full recovery of LVEf. Recovery of LV function was less likely to occur if the baseline LV impairment was lower. During follow up, 17 patients had at least one MACE (LVAD implant, cardiac transplant or death). Sinus tachycardia at diagnosis was associated with lesser chance of LV functional recovery (Table 3).     As one may expect, the majority of the women with MACE had baseline LVEf = <30% (n=14). Patients with LVEf <25% at baseline were 7x more likely to experience MACE. Six women required LVAD implant and 2 women required cardiac transplantation. A substantial number of women died (n=11, 13%) despite medical treatment for heart failure and it is unclear from the data presented what the causes of death were. It is unclear from the data which patients received an implantable defibrillator +/- CRT therapy.   Conclusions This retrospective analysis suggests that sinus tachycardia in the pregnant woman, particularly a rate > 110 per minute, in the absence of other reversible causes, may be a ‘red flag’ finding. Resting heart rate alone is an imperfect measure and only 61% of patients with PPCM had a sinus tachycardia at diagnosis. However, a sinus tachycardia should stimulate focussed clinical assessment for signs of heart failure; possibly measure natriuretic peptide levels and to perform an echo to fully assess ventricular function.   

Pregnancy outcomes in women with a systemic right ventricle and transposition of the great arteries results from the ESC-EORP Registry of Pregnancy and Cardiac disease (ROPAC)   Oktay Tutarel , Lucia Baris, Werner Budts, Mohamad Gamal Abd-El Aziz, Csilla Liptai, David Majdalany, Silvana Jovanova, Alexandra Frogoudaki, Heidi M Connolly, Mark R Johnson, Aldo P Maggioni , Roger Hall, Jolien W Roos-Hesselink on behalf of the ROPAC Investigators Group Heart 2022;108:117–123. http:// dx. doi.org/ 10. 1136/ heartjnl-2020-318685   Take Home Points: Maternal mortality was zero Heart failure and arrhythmias are the most common complication of pregnancy There appears to be no major change in the systemic RV due to pregnancy Commentary Transposition of the great arteries (TGA) repaired with an atrial switch and congenitally corrected transposition of the great arteries (CCTGA) represent a cohort of the more complex patients with congenital heart disease often with difficult to manage heart failure and arrhythmias. There have been concerns about women with a systemic right ventricle becoming pregnant and the sequalae on the right ventricle. The ROPAC registry as part of a wider review of pregnancy outcomes offers some insight into this cohort.   Methods From 2007 to 2018 pregnant patients with a variety of cardiac conditions were enrolled prospectively and from this cohort women with TGA or CCTGA were then identified making sure only those with a systemic RV were included and baseline characteristics recorded. End points for analysis were maternal death, arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischaemic coronary events and thromboembolic events. Secondary end points were adverse foetal or neonatal outcomes.   Results A total of 162 women were analysed as part of the study, TGA- 121 and CCTGA-41. The majority of women (73%) had relatively well-preserved systemic RV function, identified as greater than 40% with less than 5% of women having signs of heart failure pre-pregnancy and most being in their first pregnancy. Major maternal outcomes are shown below:   OutcomeAllCCTGATGAp-valueMaternal mortality000NaHospital admission9.8%19.5%6.6%0.03Heart failure9.8%12.2%9.1%0.56SVT3.1%04.1%0.33VT3.7%4.9%0.8%0.64Thromboembolism1.8%4.9%0.8%0.16   The most common mode of delivery was a vaginal delivery for women with a systemic RV (51.5%). There was no significant change in the amount of tricuspid regurgitation in women with scan pre-and post-pregnancy nor in RV dimensions. Adverse maternal outcomes on univariate analysis were associated with women with pre-existing heart failure symptoms or systemic ventricular function less than 40%.   Obstetric and foetal outcomes are shown below:   OutcomeAllCCTGATGAp-valueCaesarean section (LSCS)48.5%61%44.6%0.07LSCS for cardiac reasons32.9%56%22.2%0.01Foetal death0.6%0%0.8%1Neonatal death0%0%0%NaPremature birth21%20%21.5%1Growth retardation4.3%2.4%5%0.68   Lower weight babies were associated as expected with maternal medication usage(p=0.01).   Discussion This study showed good outcomes for women with a systemic right ventricle thought with symptomatic heart failure observed in 10% of women. Compared to historical data adverse outcomes in ROPAC were lower which is useful in the counselling of women. Compared to previous studies, the lack of progression in RV dysfunction was reassuring. Surprisingly, CCTGA was associated with more hospital admissions and more LSCS for cardiac reasons that TGA which was the opposite to previously reported studies and reasons for this are unclear thought the amount of women with a pacemaker was higher in the CCTGA group. Further studies with more detailed echo follow up are needed to assess the systemic RV in pregnancy.   

Adverse Pregnancy Outcomes and Incident Heart Failure in the Women’s Health Initiative   Take Home Points: Adverse pregnancy outcomes (APO) complicate up to 30% of pregnancies. Prior studies suggest that preeclampsia, hypertensive disorders of pregnancy and gestational diabetes may be associated with an increased risk of developing heart failure (HF), yet the potential impact of multiple APOs on heart failure occurrence and whether there is difference on the occurrence on heart failure with reduced ejection fraction (HFrEF) versus on heart failure with preserved ejection fraction (HFpEF) are unknown. The aim of the study was to assess individual and joint associations between APOs in pregnancies lasting >6 months and HF using the Women’s Health Initiative (WHI) database. The WHI initiative is a longitudinal study of ethnically diverse postmenopausal women aged 50 to 79 years at entry that were recruited from 40 US clinical centers between 1993 and 1998 and followed prospectively. The APOs evaluated were gestational diabetes, preeclampsia, hypertensivedisordr of pregnancy, preterm delivery (<37 weeks), low birth weight (<2,500 grams), and high birth weight (>4500 g). More than 1 APO may have occurred in the same woman, but not necessarily during the same pregnancy. A total of 10,292 patients at an average age of 60 years responded to a questionnaire inquiring on past history of APO’s sent to their homes, and comprised of the study population. Of those, 3185 (31.0%) reported a history of 1 or more APOs, the most frequently reported being preterm delivery (14.7%), followed by low birth weight (13.8%), hypertensive disorder (7.4%), high birth weight (6.3%), and gestational diabetes (2.5%). The most common combination of APOs in the study population was preterm delivery and low birth weight (7.1%). Baseline characteristics of the study participants at the time of responding to the questionnaires differed by the history and type of APO. Patients with history of any APO had a higher prevalence of risk factors such as higher BMI, coronary artery disease, hypertension, diabetes, smoking (>20 pack-years), history of stillbirth, lower levels of education and household income, younger age at first birth and older age at menopause, were less likely to have reported a history of breastfeeding, miscarriage, and menstrual cycle irregularity; and reported fewer live births. Of the study cohort, 336 (3.3%) patients had a diagnosis of HF, 180 (1.8%) had HFpEF, and 111 (1.1%) had HFrEF (it is unclear if in the remaining 45 patients the EF was unavailable, or if they had HFmrEF) . Women with a history of APO had a higher rate of HF than those without a history of APO (3.8% vs 2.9%, statistical significance is not provided). Women with history of hypertensive disorder of pregnancy, which was more common among black women, had the highest rate of HF (5.1%), and women with gestational diabetes had the lowest rate of HF (3.1%). Hypertensive disorder of pregnancy was the only APO with a significant association with HF in univariate models, and remained significantly associated with HF after adjusting for a model consisting of age, sociodemographic factors, smoking, randomization status, other subsequent APOs and reproductive history (OR, 1.75). In analyses of HF subtypes, only history of hypertensive disorder of pregnancy was significantly associated with HFpEF in a fully adjusted model (OR, 2.06), but not with HFrEF. There was no significant modification of the association of history of hypertensive disorder of pregnancy with HF by covariates including other APOs. Upon excluding women with history of coronary artery disease, the association between HDP and HF was similar Commentary from Dr. Yonatan (Seattle, USA), section editor of Cardio-Obstetrics Journal Watch: The main strengths of the study are the large cohort included in it and the ability to identify outcomes and non-APO risk factors through the large and well established WHI database. The association between hypertensive disorder of pregnancy and the development of heart failure, which have been previously described in other works, are nicely reinforced by the authors, who also provide the mechanism for this association in their discussion.   Heart failure and hypertensive disorder of pregnancy have shared risk factors, such as chronic hypertension and obesity and which may underlie the association between hypertensive disorders of pregnancy and future occurrence of HF. In addition, hypertensive disorder of pregnancy, compared to normotensive pregnancies, was shown to be associated with several cardiac abnormalities that can lead to HF, including left ventricular remodeling and microvasculature changes, impaired diastolic function, and impaired coronary flow reserve.   Gestational diabetes was shown in prior works to be a pertinent risk factor for the development of HF, yet in this study this association has not been established. It is possible that the relatively low prevalence of gestational diabetes in the cohort included in this study is the main reason for this difference.   Limitations of the study include its retrospective nature with the associated survivorship bias among the included sample, who needed to survive until the APO survey was performed, the author’s inability to validate the obstetric records, and the inability to differentiate whether women had multiple APOs in the same pregnancy or in recurrent pregnancies.   In summary, in a large cohort of postmenopausal women included in the WHI registry, history of hypertensive disorders of pregnancy was the only APO associated with HF occurrence, primarily HFpEF . As stated by the authors, this represents an opportunity for early, aggressive, preventive interventions for HF and other CVD, possibly before development of the traditional risk factors (hypertension, diabetes, and obesity).