Open access Coronary artery disease Open Heart: first published as 10.1136/openhrt-2020-001273 on 6 August 2020. Downloaded from Left ventricular mass and myocardial scarring in women with hypertensive disorders of pregnancy Odayme Quesada,1,2 Ki Park,3 Janet Wei,1,2 Eileen Handberg,3 Chrisandra Shufelt,1,2 Margo Minissian,1,2 Galen Cook- Wiens,4 Parham Zarrini,1,2 Christine Pacheco ,1,2 Balaji Tamarappoo,1 Louise E J Thomson,5 Daniel S Berman,5 Carl J Pepine,3 Noel Bairey Merz 1,2 To cite: Quesada O, Park K, ABSTRACT Key questions Wei J, et al. Left ventricular Aims Hypertensive disorders of pregnancy (HDP) predict mass and myocardial scarring in future cardiovascular events. We aim to investigate women with hypertensive What is already known about this subject? relations between HDP history and subsequent disorders of pregnancy. Open Hypertensive disorders of pregnancy (HDP) are as- hypertension (HTN), myocardial structure and function, and ► Heart 2020;7:e001273. sociated with increased risk of cardiovascular dis- late gadolinium enhancement (LGE) scar. doi:10.1136/ ease and mortality. openhrt-2020-001273 Methods and results We evaluated a prospective cohort of women with suspected ischaemia with no obstructive What does this study add? coronary artery disease (INOCA) who underwent stress/ ► Our study demonstrates higher left ventricular mass OQ and KP contributed equally. rest cardiac magnetic resonance imaging (cMRI) with in women with HDP and concomitant hypertension LGE in the Women’s Ischemia Syndrome Evaluation- Received 20 February 2020 (HTN) history and a trend towards larger LGE myo- Coronary Vascular Dysfunction study. Self- reported history Revised 15 May 2020 cardial scar size in women with HDP. Future stud- Accepted 2 June 2020 of pregnancy and HDP (gestational HTN, pre-ec lampsia, ies are needed to better assess the relationship of toxaemia and eclampsia) were collected at enrollment. In HDP and left ventricular morphology and myocardial our cohort of 346, 20% of women report a history of HDP. scarring in a larger cohort of women. HDP history was associated with 3.2-fold increased odds of HTN. Women with a history of both HDP and HTN had How might this impact on clinical practice? ► Our findings support HTN surveillance in women higher cMRI measured left ventricular (LV) mass compared http://openheart.bmj.com/ with women with HDP only (99.4±2.6 g vs 87.7±3.2 g, with HDP who may be at higher risk for abnormali- p=0.02). While we found a similar frequency of LGE scar, ties in cardiac morphology. we observed a trend towards increased LGE scar size (5.1±3.4 g vs 8.0±3.4 g, p=0.09) among the women with © Author(s) (or their HDP history compared to women without. understood, large cohort studies have found employer(s)) 2020. Re- use Conclusion In a high- risk cohort of women with that pre- eclampsia is associated with up to an permitted under CC BY. suspected INOCA, 20% had a history of HDP. Women with eightfold higher risk of CVD and mortality Published by BMJ. HDP history were more likely to develop HTN. Our study compared with women with healthy normo- 1Smidt Heart Institute, Cedars- demonstrates higher LV mass in women with HDP and tensive pregnancies.4–8 These findings empha- on September 29, 2021 by guest. Protected copyright. Sinai Medical Center, Los concomitant HTN. Although the presence of LGE scar sise the importance of understanding women- Angeles, California, USA was not different in women with and without HDP history, 2Barbra Streisand Women's specific risk factors for CVD. we observed a trend towards larger scar size in women Heart Center, Cedars- Sinai Cardiac magnetic resonance imaging with HDP. Future studies are needed to better assess the Medical Center, Los Angeles, (cMRI) with late gadolinium enhancement relationship of HDP and cardiac morphology and LGE California, USA (LGE) can be used to evaluate ventricular 3 scarring in a larger cohort of women. Cardiovascular Medicine, morphology and function, detect myocardial University of Florida College of scar and quantify scar size with high accu- Medicine, Gainesville, Florida, 9 10 USA racy. cMRI measures, particularly increased 4Biostatistics and Bioinformatics INTRODUCTION left ventricular (LV) mass, presence of isch- Research Center, Cedars- Sinai Increasing evidence has led to a wider recog- aemic and non- ischaemic scar as determined Medical Center, Los Angeles, nition of women- specific risk factors for by LGE imaging are independent risk factors California, USA 11–16 5 cardiovascular disease (CVD). These include S Mark Taper Foundation for major adverse cardiovascular events. Imaging Center, Cedars- Sinai hypertensive disorders of pregnancy (HDP), Research on the associations between HDP Medical Center, Los Angeles, such as gestational hypertension (HTN) and and CVD is limited. Therefore, we investigated California, USA pre-eclampsia, which combined complicate the risk of developing HTN decades after the up to 10% of pregnancies and are character- index pregnancy complicated by HDP and Correspondence to Dr Noel Bairey Merz; merz@ ised by de novo HTN after 20 weeks gesta- relationship of history of HDP and HTN with 1–3 cshs. org tion. Although the pathophysiology is poorly cMRI measured LV morphology and function, Quesada O, et al. Open Heart 2020;7:e001273. doi:10.1136/openhrt-2020-001273 1 Open Heart Open Heart: first published as 10.1136/openhrt-2020-001273 on 6 August 2020. Downloaded from and presence and size of LGE myocardial scar in women cMRI protocol and analyses with ischaemia with no obstructive coronary artery disease Stress and rest cMRI were performed at time of enrollment (INOCA) in the Women’s Ischemia Syndrome Evaluation- on a 1.5-T esla MR scanner (Magnetom Avanto, Siemens Coronary Vascular Dysfunction (WISE- CVD) cohort.17 We Healthcare Erlangen, Germany) in the supine position hypothesise that women with HDP history will have abnor- with ECG gating. All subjects were asked to hold all their malities in LV morphology and function and more likely to cardiac medications 24–48 hours prior to cMRI. A highly have LGE myocardial scar. standardised protocol was used and included assessment of ventricular function and morphology and LGE imaging.18 In brief, LGE images were acquired in 10–12 short axis METHODS slices, one horizontal long axis slice and one vertical long Study population axis slice in the same positions as the LV function cine This investigation was part of the National Heart, Lung, images. A single shot trufi- based sequence was used with and Blood Institute- sponsored prospective multicentre heart rate- based temporal resolution and echo time mini- WISE- CVD study (URL: http://www. clinicaltrials. gov, mised at 0.98 ms. A ‘TI scout’ image was obtained followed unique identifier: NCT00832702). WISE-CVD was a by single shot inversion recovery TrueFISP images 10 min prospective study of women with suspected sign and symp- after last gadolinium injection. toms of INOCA (defined as <50% luminal diameter in any 18 The WISE- cMRI core lab analysed LV function and major coronary artery) on invasive angiography. Subjects morphology using commercially available software were recruited from January 2009 to August 2015 at Cedars- (CAAS MRV V.3.4, PIE Medical Imaging) as previously Sinai Medical Center, Los Angeles, California or University described.20–22 Epicardial and endocardial borders of short- of Florida, Gainesville, Florida. The protocol was approved axis cine images were manually traced and postprocessing by the Institutional Review Board at each site and all partic- software was used to generate volume–time curves used for ipants provided written informed consent. LV volumes and LV mass. Stroke volume was calculated As previously described women with signs and symptoms as end- diastolic volume minus end-systolic, and ejection of ischaemia undergoing clinically indicated coronary angi- fraction as stroke volume divided by end-diastolic volume. ography, age ≥21 years and competent to give informed LGE quantification was performed by a single experi- consent were included. Exclusion criteria included acute enced operator using associated postprocessing software coronary syndrome (defined by the American College of 19 (QMass, Medis) by defining endocardial and epicardial Cardiology/American Heart Associationcriteria), acute borders using the short- axis images and the full width at myocardial infarction; concurrent cardiogenic shock or half- maximum method. LGE myocardial scar pattern was inotropic or intra-aortic balloon support; prior or planned evaluated visually and defined as atypical scar pattern when percutaneous coronary intervention or coronary artery mid- myocardial or epicardial scar pattern was present; and http://openheart.bmj.com/ bypass graft (CABG); primary valvular heart disease clearly typical scar pattern when scar pattern was subendocardial indicating need for valve repair or replacement; chest pain or transmural and localised to a coronary artery distribu- with a non-ischaemic aetiology (eg, pericarditis, pneu- tion as previously described.23 monia, oesophageal spasm); conditions that preclude accurate or safe testing, or prognostic follow-up, specifically Statistical analyses contraindications to cMRI (eg, implantable cardioverter The 346 women with a pregnancy history were divided into defibrillator, pacemaker, untreatable claustrophobia or two groups: those with HDP and those without. Variables known angio- oedema, severe renal impairment (estimated were summarised using mean and SD, or frequency and glomerular filtration rate (eGFR) <45 mL/min); prior non- per cent if categorical, median and IQR was used to report on September 29, 2021 by guest. Protected copyright. cardiac illness with an estimated life expectancy <4 years; LGE myocardial scar size. Baseline clinical and demo- and obstructive coronary artery disease defined as ≥50% graphic variables were tested between these two groups luminal diameter stenosis in ≥1 epicardial coronary artery, 2 18 using Pearson χ tests, or Fisher’s exact test for categorical assessed visually at the time of angiography.