Background Myocarditis is a potentially severe adverse event after COVID-19 messenger RNA (mRNA) vaccination. Validation of reported cases is essential. We aimed to determine the occurrence, clinical characteristics and short-term outcomes of vaccine-associated myocarditis (VAM) in Norway.Methods In this nationwide, population-based validation study, we used national health registry data and hospital electronic medical records from 27 December 2020 to 30 April 2022. We identified all Norwegian residents who received at least one dose of BNT162b2 or mRNA-1273. By cross-linking registries, we identified myocarditis within 90 days after vaccination. Diagnoses were validated through individual chart review using Brighton Collaboration criteria. VAM was defined as myocarditis without a more likely alternative cause.Results Among 4.1 million vaccinated individuals who received 10.9 million doses, we identified 367 potential myocarditis cases. Of 349 cases reviewed, 177 (51%) were validated as VAM, corresponding to 4.5 cases per 100 000 vaccinated individuals. In total, 110 (62%) cases occurred after the second dose. Of validated cases, 139 (79%) occurred in men. Median age was 30 (IQR 24–50) years for men and 54 (IQR 32–65) years for women. Three (2%) cases were under 18 years. The median hospital stay was 4 (IQR 3–5) days, and the median ejection fraction was 55% (IQR 53%–60%). Seven (4%) patients required intensive care and two (1%) older patients died. No patient required mechanical circulatory support or heart transplantation.Conclusions VAM occurred in 4.5 per 100 000 vaccinated individuals, based on validation of about half of registry-identified myocarditis cases. The acute clinical course was generally mild. National surveillance and systematic validation are essential for reliable estimates of vaccine-associated adverse events.Trial registration number NCT05610423.
BACKGROUND:The hemodynamic changes during pregnancy can be challenging in women with underlying heart disease, particularly in women with impaired left ventricular function (LVF, left ventricular ejection fraction <40%). OBJECTIVES:The aim of this study was to describe the cardiac, obstetric, and fetal outcomes of pregnancy in women with impaired LVF. METHODS:ROPAC (Registry Of Pregnancy and Cardiac disease) includes an international, prospective, observational cohort of pregnancies in women with heart disease. Cardiac, obstetric, and fetal outcomes were analyzed in 251 patients with impaired LVF. The primary endpoint was the occurrence of major adverse cardiac events (MACE) including maternal death, supraventricular or ventricular arrhythmias, heart failure, aortic dissection, endocarditis, ischemic coronary event, and other thromboembolic events. Logistic regression was used to determine variables associated with poor outcomes. RESULTS:Median follow-up duration was 7 (6-11) months. Maternal mortality occurred in 6/251 (2.4%, 1%-5%) and heart failure in 67/251 (27%, 21%-33%) patients. Ventricular tachyarrhythmias occurred in 11/251 (4%, 2%-8%) patients. Eighty-one of 251 (32%, 27%-38%) patients experienced at least one MACE during pregnancy or up to 6 months postpartum. Obstetric complications were common, including preterm birth in 67/251 (27%, 22%-33%) and low birthweight in 65/251 (26%, 21%-32%). Patients with cardiomyopathy were at higher risk of cardiovascular complications with 4.3% mortality and nearly 40% risk of MACE during pregnancy. Prepregnancy signs of heart failure (OR: 2.67; 1.3-5.6), atrial fibrillation (OR: 6.32; 3.0-13.3), and an NYHA functional class >II (OR: 6.06; 2.2-16.6) were associated with poor cardiac outcomes. CONCLUSIONS:Women with impaired LVF are at increased risk of complications, particularly heart failure, tachyarrhythmias, and premature delivery with low birth weight.
ObjectiveEpidemiological studies show an increased risk for premature maternal cardiovascular disease in women after pregnancy complications, like preeclampsia, gestational hypertension and gestational diabetes mellitus. Our goal was to create a novel “digital companion” for women with such pregnancy complications, in the format of a mobile health-assisted user-centered follow-up software application (app).MethodsA cardiovascular postpartum follow-up program was developed as a digital companion, including a new mobile application (app), which is based on Norwegian obstetric and international guidelines. The MumCare app was developed through a co-creation process that included users, stakeholders, and clinical experts. Five qualitative interviews and 10 qualitative co-creative user testing interviews were conducted throughout the development stages to improve the perceived usefulness of the companion. The objective of the present study was to analyze the iterative co-creation process including users, stakeholders and clinical experts.ResultsPhase 1 involved developing the companion within an interdisciplinary expert group through an iterative process in close dialogue with users. Explorative user interviews in Phase 2 (n = 5) supported the translation of guidelines into a structured app format, visualized as MumCare sketches for design, functionality and user communication. During Phase 3, the app sketches were revised in collaboration with users, in application interviews (n = 7). During Phase 4, the programmed prototype was refined through feedback from pilot users (n = 3). The user groups highlighted several app benefits, including a follow-up system of personal modifiable risk factors, a user-friendly system for tracking blood pressure over time, with individualized feedback and prompts. The use of non-ambiguous language and symbols was appreciated among users, who also contributed new content items to the app.ConclusionUser-centered co-creation improved several important features during the companion development process. The MumCare app is being tested in a prospective randomized controlled clinical trial that started in June 2024. Clinical trial registrationClinicaltrials.gov reg., identifier NCT05835596.
BACKGROUND:Peripartum cardiomyopathy (PPCM) occurs in 0.02% to 0.1% of live births in European countries. Truncating variants in the Titin gene (TTNtv) are the most common genetic findings in women with PPCM. However, data on pregnancy-associated cardiomyopathy (PAC) and pregnancy tolerance among TTNtv-positive women are limited. OBJECTIVES:The objectives of the study were to report maternal cardiac outcomes during pregnancy and postpartum and fetal outcomes in women with TTNtv and to explore the effect of parity on long-term cardiac phenotype. METHODS:We conducted an ambispective cohort study including consecutive TTNtv genotype-positive women, regardless of phenotype, with ≥1 cardiological evaluation. Data on pregnancies and maternal and fetal outcomes were collected from questionnaires and medical records. Arrhythmic burden and device implantation were recorded. Left ventricular dimensions and function were assessed by echocardiography. RESULTS:A total of 107 TTNtv-positive women were included (age 43 [IQR: 32-55] years, 17% probands). Among 78 women with prior pregnancies, 206 pregnancies resulted in 167 (81%) live births. PAC occurred in 3 of 167 live births and in 3 of 76 women, corresponding to a cumulative incidence of 1.8% and 3.9%. All affected women recovered completely with medical therapy. Remaining pregnancies were largely uncomplicated, without increased maternal or fetal adverse events. At median of 18 years (IQR: 9-31) after pregnancy, no differences were observed between parous and nulliparous women in arrhythmic burden, cardiac function, or ventricular dimensions. CONCLUSIONS:In this TTNtv-positive cohort, PAC incidence appeared higher than reported PPCM rates in the general European population. However, pregnancy was well tolerated and was not associated with adverse long-term cardiac remodeling.
INTRODUCTION:Women with cardiovascular disease may be at increased risk of hypertensive disorders of pregnancy (HDP). We aimed to: (1) Investigate the occurrence of HDP in a cohort of pregnant women with cardiovascular disease and compare it with the occurrence in the general population. (2) Assess the association between maternal cardiovascular risk and risk of HDP. MATERIAL AND METHODS:We reviewed clinical data on a cohort of 901 pregnancies among 708 women with cardiovascular disease who were followed at the National Unit for Pregnancy and Heart Disease and gave birth at Oslo University Hospital between 2003 and 2018. The exposure under study was maternal cardiovascular risk, classified as low, moderate, or high based on a modified classification by the World Health Organization. The main outcome of interest was HDP, which included pre-eclampsia and gestational hypertension. The proportion of HDP cases in the general population in the same period was extracted from the Medical Birth Registry of Norway. We used logistic regression to estimate crude and adjusted odds ratios (OR) of HDP, with associated 95% confidence intervals (CIs), for women with moderate- and high cardiovascular risk compared to women with low risk. RESULTS:The occurrence of HDP in the study cohort was 12.1% (95% CI: 10.0%-14.4%) and varied between 8.7% (95% CI: 6.5%-11.3%) in the low-risk group, 15.7% (95% CI: 11.1%-21.4%) in the moderate-risk group, and 22.2% (95% CI: 15.1%-30.8%) in the high-risk group. By contrast, the nationwide occurrence of HDP was 5.1% (95% CI: 5.1%-5.2%). In the study cohort, the proportions of pregnancies with gestational hypertension and pre-eclampsia were similar (6.3% and 5.8%, respectively). Compared to pregnancies with low cardiovascular risk, the adjusted OR of HDP was 2.04 (95% CI: 1.21-3.44) in the moderate-risk group and 2.99 (95% CI: 1.73-5.18) in the high-risk group. CONCLUSIONS:The occurrence of hypertensive disease of pregnancy in the study cohort was more than doubled compared to the general population in Norway. The risk of HDP increased with maternal cardiovascular risk group. We recommend taking into account maternal cardiovascular risk group when assessing risk and prophylaxis of HDP.
Background: More women with congenital heart disease (CHD) reach reproductive age, but little is known of their success in having children. We investigated time trends of CHD in women of reproductive age and maternal CHD in childbirth and compared birth rates in women with CHD to birth rates in women without heart disease. Methods and results: In a national cohort, we combined information from five registries in Norway 1994 -2014. Among 1,644,650 women aged 15 -45 years, 5672 had CHD. Among 1,183,851 childbirths, 3504 were registered with maternal CHD. The prevalences of mild and moderate/severe CHD in women increased by an average of 3 -4% per year 1994 -2014, as did the prevalences of mild and moderate/severe maternal CHD in childbirth. Compared to women without heart disease, the likelihood of having children was similar for women with mild CHD (rate ratio 1.03, 95% confidence interval 0.97 -1.09) but lower for women with moderate/severe CHD (rate ratio 0.75, 95% confidence interval 0.68 -0.84). The mean number of childbirths was similar in women with mild CHD and women without heart disease (1.81 vs 1.80, p = 0.722) but lower in women with moderate/severe CHD (1.42, p < 0.001). Conclusion: In a national cohort over two decades of women of reproductive age, the prevalence of maternal CHD in childbirth reflected the increasing prevalence of CHD in the population. Birth rates were similar for women with mild CHD and women without heart disease, whereas women with moderate/severe CHD were less likely to have children and had a lower mean number of childbirths.
Abstract Background The SARS-CoV-2 pandemic led to worldwide initiation of vaccination campaigns. The new mRNA vaccines were unexpectedly associated with vaccine-associated myocarditis (VAM). The incidence and severity of VAM has not been validated in a nation-wide and well-defined population. From December 2020 onwards the mRNA vaccines Comirnaty and Spikevax have been in widespread use in Norway. The National Patient Register (NPR) includes all hospital contacts with corresponding diagnostic codes (ICD-10), and all vaccinations are registered in the Norwegian Immunization Register (SYSVAK). Purpose We aimed to identify and validate all cases of suspected COVID-19 VAM in Norway during the national vaccination campaign between 2020-22. Methods We identified all cases of myocarditis acquired within 90 days of a COVID-19 vaccination through linkage of diagnostic codes for myocarditis in NPR and vaccination data in SYSVAK. Cases were included from December 2020 through April 2022. We assessed medical records, cardiac imaging, and biochemistry to retrospectively validate all myocarditis cases. The Brighton Criteria (international criteria for myocarditis diagnosis following immunization with defining levels of diagnostic certainty) were used to confirm the VAM diagnosis. Results From December 2020 to April 2022, 4 114 750 unique subjects (2 036 792 men and 2 077 958 women, median age first dose 47 years) above 16 years of age, received 10 915 098 unique doses of COVID-19 vaccines (8 651 703[79%] Comirnaty and 2 263 395[21%] Spikevax). Of 277 cases of myocarditis identified in NPR<90 days after receiving a COVID-19 vaccine, 176(64%) were validated as VAM (78 definite, 90 probable, and 8 possible VAM). Among the patients with VAM, 137(78%) were men with median age 30(IQR 24-47) years, and 39(22%) were women with median age 54(IQR 32-65) years. There were 4 cases of VAM per 100 000 vaccinated subjects: 7 per 100 000 men and 2 per 100 000 women. Sixty-three percent of VAM occurred after the second mRNA vaccine dose. There were 3.3 cases of VAM per 100 000 unique doses of Spikevax compared to 1.1 per 100 000 unique doses of Comirnaty. The most common time interval from vaccination to VAM was 3 days and occurred in 30 patients (17.3% of VAM, 93% men), and 34% of VAM (90% men) occurred during the first 5 days from vaccination(Figure). Median duration of hospital stay was 4(IQR 3-5) days, with only 7(4%) patients needing intensive care and 1 myocarditis related patient death during hospitalization. Conclusions In this unique nationwide study including all COVID-19 vaccinated subjects in Norway from 2020-22 we found 4 cases of VAM per 100 000 vaccinated subjects. The majority of VAM occurred in young men. Interestingly, women presented later than men with VAM and most frequently at middle to older age. The occurrence of this unexpected serious adverse event underscores the importance of large studies in broad populations in future vaccine programs.
BACKGROUND A comprehensive understanding of adult congenital heart disease outcomes must include psychological functioning. Our multisite study offered the opportunity to explore depression and anxiety symptoms within a global sample. OBJECTIVES In this substudy of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults With Congenital Heart Disease-International Study), the authors we investigated the prevalence of elevated depression and anxiety symptoms, explored associated sociodemographic and medical factors, and examined how quality of life (QOL) and health status (HS) differ according to the degree of psychological symptoms. METHODS Participants completed the Hospital Anxiety and Depression Scale, which includes subscales for symptoms of anxiety (HADS-A) and depression (HADS-D). Subscale scores of 8 or higher indicate clinically elevated symptoms and can be further categorized as mild, moderate, or severe. Participants also completed analogue scales on a scale of 0 to 100 for QOL and HS. Analysis of variance was performed to investigate whether QOL and HS differed by symptom category. RESULTS Of 3,815 participants from 15 countries (age 34.8 +/- 12.9 years; 52.7% female), 1,148 (30.1%) had elevated symptoms in one or both subscales: elevated HADS-A only (18.3%), elevated HADS-D only (2.9%), or elevations on both subscales (8.9%). Percentages varied among countries. Both QOL and HS decreased in accordance with increasing HADS-A and HADS-D symptom categories (P < 0.001). CONCLUSIONS In this global sample of adults with congenital heart disease, almost one-third reported elevated symptoms of depression and/or anxiety, which in turn were associated with lower QOL and HS. We strongly advocate for the implementation of strategies to recognize and manage psychological distress in clinical settings.
OBJECTIVE:Valvular heart diseases (VHDs) pose a significant public health burden, and deciding the best treatment strategy necessitates accurate assessment of heart valve function. Transthoracic echocardiography (TTE) is the key modality to evaluate VHDs, but the lack of standardized quantitative measurements leads to subjective and time-consuming assessments. We aimed to use deep learning to automate the extraction of mitral valve (MV) leaflets and annular hinge points from echocardiograms of the MV, improving standardization and reducing workload in quantitative assessment of MV disease.METHODS:We annotated the MV leaflets and annulus points in 2931 images from 127 patients. We propose an approach for segmenting the annotated features using Attention UNet with deep supervision and weight scheduling of the attention coefficients to enforce saliency surrounding the MV. The derived segmentation masks were used to extract quantitative biomarkers for specific MV leaflet scallops throughout the heart cycle.RESULTS:Evaluation performance was summarized using a Dice score of 0.63 ± 0.14, annulus error of 3.64 ± 2.53 and leaflet angle error of 8.7 ± 8.3°. Leveraging Attention UNet with deep supervision robustness of clinically relevant metrics was improved compared with UNet, reducing standard deviations by 2.7° (angle error) and 0.73 mm (annulus error). We correctly identified cases of MV prolapse, cases of stenosis and healthy references from a clinical material using the derived biomarkers.CONCLUSION:Robust deep learning segmentation and tracking of MV morphology and motion is possible by leveraging attention gates and deep supervision, and holds promise for enhancing VHD diagnosis and treatment monitoring.
Ferroptosis plays a key role in placental development and physiology, and abnormal ferroptosis has been implicated in trophoblast injury leading to preeclampsia (PE). We hypothesize that leukocytes isolated from PE exhibit increased ferroptosis and that extracellular vesicles contain long non-coding (lnc) RNA/mRNAs that modulate oxidative stress and iron toxicity in vascular endothelial cells. We measured the expression of key regulators of ferroptosis in leukocytes and extracellular vesicles as well as circulating biomarkers of iron homeostasis and oxidative stress in plasma from women with/without PE at different timepoints during pregnancy. For markers that were dysregulated, we assessed their temporal correlation with established markers of disease activity and marker of endothelial activation. For markers dysregulated in early pregnancy, we assessed their ability to predict the development of PE. We found decreased lncRNA/mRNAs in leukocytes, but not extracellular vesicles, in PE that may modulate oxidative stress and iron toxicity. This decrease in anti-ferroptotic markers does not appear to be related to maternal disease activity or plasma oxidative stress status but rather to attenuated anti-inflammatory expression in these cells. Circulating ferritin was elevated in PE, supporting the hypothesis that PE represents a disbalance in iron homeostasis. Low lncRNA taurine upregulated gene 1 RNA levels in leukocytes at 22–24 weeks were strongly associated with the development of PE. Our findings suggest that maternal leukocytes in PE show decreased anti-ferroptotic activity that correlates with anti-inflammatory expression. Moreover, some of these changes in ferroptotic activity appear to precede the development of PE.
OBJECTIVES:This study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe. METHODS:A questionnaire was sent to ACHD cardiologists from 34 European countries. RESULTS:Representatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors 'on the job'. The median number of ACHD centres per country was 4 (range 0-28), median number of ACHD surgical centres was 3 (0-26) and the median number of ACHD training centres was 2 (range 0-28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001). CONCLUSION:Formal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to 'train people on the job'. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care.
BACKGROUND:Ferroptosis plays a key role in placental development and physiology, and abnormal ferroptosis has been implicated in trophoblast injury leading to preeclampsia (PE). We hypothesize that leukocytes isolated from PE exhibit increased ferroptosis and that extracellular vesicles contain long non-coding (lnc) RNA/mRNAs that modulate oxidative stress and iron toxicity in vascular endothelial cells. METHODS:We measured the expression of key regulators of ferroptosis in leukocytes and extracellular vesicles as well as circulating biomarkers of iron homeostasis and oxidative stress in plasma from women with/without PE at different timepoints during pregnancy. For markers that were dysregulated, we assessed their temporal correlation with established markers of disease activity and marker of endothelial activation. For markers dysregulated in early pregnancy, we assessed their ability to predict the development of PE. RESULTS:We found decreased lncRNA/mRNAs in leukocytes, but not extracellular vesicles, in PE that may modulate oxidative stress and iron toxicity. This decrease in anti-ferroptotic markers does not appear to be related to maternal disease activity or plasma oxidative stress status but rather to attenuated anti-inflammatory expression in these cells. Circulating ferritin was elevated in PE, supporting the hypothesis that PE represents a disbalance in iron homeostasis. Low lncRNA taurine upregulated gene 1 RNA levels in leukocytes at 22-24 weeks were strongly associated with the development of PE. CONCLUSIONS:Our findings suggest that maternal leukocytes in PE show decreased anti-ferroptotic activity that correlates with anti-inflammatory expression. Moreover, some of these changes in ferroptotic activity appear to precede the development of PE.
Aims To objectively study cardiorespiratory fitness (CRF) and physical activity (PA) and to evaluate limiting factors of exercise intolerance associated with poor CRF after severe pre-eclampsia. Methods In this single-centre, cross-sectional study, CRF was measured as peak oxygen uptake (VO2peak) during a cardiopulmonary exercise test (CPET) on a treadmill in women 7 years after severe pre-eclampsia. Ninety-six patients and 65 controls were eligible to participate. Cardiac output (CO) was measured by impedance cardiography. PA was measured using accelerometers. Results In 62 patients and 35 controls (mean age 40 & PLUSMN; 3 years), the VO2peak (in mL & BULL;kg-1 & BULL;min-1) values were 31.4 & PLUSMN; 7.2 and 39.1 & PLUSMN; 5.4, respectively (p<0.01). In the patients, the COpeak was (9.6 L & BULL;min-1), 16% lower compared to controls (p<0.01). Twelve patients (19%) had a cardiac limitation to CPET. Twenty-three (37%) patients and one (3%) control were classed as unfit, with no cardiopulmonary limitations. The patients demonstrated 25% lower PA level (in counts per minute; p<0.01) and 14% more time being sedentary (p<0.01), compared with the controls. Twenty-one patients (34%) compared with four (17%) controls did not meet the World Health Organization's recommendations for PA (p=0.02). Body mass index and PA level accounted for 65% of the variability in VO2peak. Conclusion Significantly lower CRF and PA levels were found in patients on long-term follow-up after severe pre-eclampsia. CPET identified cardiovascular limitations in one third of patients. One third appeared unfit, with adiposity and lower PA levels. These findings highlight the need for clinical follow-up and exercise interventions after severe pre-eclampsia.
Aims The aim was to study pregnancy outcomes in women with coarctation of the aorta (CoA) and associations to hypertensive disorders of pregnancy. Maternal morbidity and mortality are higher in women with heart disease and pre-eclampsia. Chronic hypertension, frequently encountered in CoA, is a risk factor for pre-eclampsia. Methods and results Clinical data from the National Unit for Pregnancy and Heart Disease database was reviewed for pregnant women with CoA from 2008 to 2021. The primary outcome was hypertensive pregnancy disorders. The secondary outcomes were other cardiovascular, obstetric, and foetal complications. Seventy-six patients were included, with a total of 87 pregnancies. Seventeen (20%) patients were treated for chronic hypertension before pregnancy. Fifteen (20%) patients developed pre-eclampsia, and 5 (7%) had pregnancy-induced hypertension. Major adverse cardiac events developed in four (5%) patients, with no maternal or foetal mortality. Maternal age at first pregnancy [odds ratio (OR) 1.37], body mass index before first pregnancy (OR 1.77), and using acetylsalicylic acid from the first trimester (OR 0.22) were statistically significantly associated with pre-eclampsia. At follow-up (median) 8 years after pregnancy, 29 (38%) patients had anti-hypertensive treatment, an increase of 16% compared to pre-pregnancy. Five (7%) patients had progression of aorta ascendens dilatation to >40 mm, seven (9%) had an upper to lower systolic blood pressure gradient >20 mmHg, and six (8%) had received CoA re-intervention. Conclusion Pre-eclampsia occurred in 20% of women with CoA in their first pregnancy. All pre-eclamptic patients received adequate anti-hypertensive treatment. All CoA patients were provided multi-disciplinary management, including cardiologic follow-up, to optimize maternal-foetal outcomes.
Objective. To study left ventricular (LV) function and blood pressure (BP) at a long-term follow-up in women after severe pre-eclampsia. Design. In this single-centre, cross-sectional study, 96 patients were eligible for inclusion. LV function was examined by transthoracic echocardiography including tissue Doppler echocardiography and speckle tracking. BP was measured at rest using repeated non-invasive techniques. Results. We compared 36 patients with early-onset and 33 patients with late-onset pre-eclampsia with 28 healthy controls. Mean age (40 +/- 3 years) and median time since delivery (7 +/- 2 years) were similar across the study groups. The patients had 18% higher systolic BP (139 +/- 15 mmHg) and 24% higher diastolic BP (87 +/- 19 mmHg) than controls (p < .01). Hypertension was present in 23 patients (33%), where the estimated LV mass was 16% higher (p = .05) than in controls. The LV ejection fraction was 19% lower in the early-onset group (51 +/- 4%; p = .01) and 14% lower in the late-onset group (54 +/- 6; p = .04) compared with controls. LV global longitudinal strain was 18% lower in the patient group (-17.7 +/- 2.1%) compared with controls (p = .01). Indicative of a more restrictive filling pattern, the diastolic indices showed a lower e ' mean (p < .01) and subsequently higher E/e ' ratio (p < .01). There were no significant differences in BP, systolic or diastolic function indices between the patient groups. Conclusion. We found sustained hypertension, higher LV mass and reduced LV systolic and diastolic function 7 y after severe pre-eclampsia. Our findings emphasize the importance of early risk stratification and clinical counselling, and follow-up for such cases.
Beta-blockers are prescribed for many pregnant women with heart disease, but whether there is a dose-dependent effect on fetal growth remains to be examined. We aimed to investigate if antenatal beta-blocker use and dose were associated with delivering a small-for-gestational-age infant among women with heart disease. Our cohort included women with heart disease who delivered at Oslo University Hospital between 2006 and 2015. Maternal heart disease was classified into modified WHO risk scores. Women with beta-blocker treatment were dichotomized into whether they had been treated with a low or high dose based on clinical factors. We compared the risk of delivering a small-for-gestational-age infant in women exposed to high doses, low doses, or with no exposure to antenatal beta-blockers while adjusting for severity of maternal heart disease in logistic regression models. Of a total of 540 pregnancies among women with heart disease, 163 (30.2%) were exposed to beta-blocker treatment. The majority were treated with metoprolol (86.5%). Almost twice as many babies in the beta-blocker group were small-for-gestational-age, compared with the non-exposed group (19.8 vs 9.5%, P < 0.001). Women using a high-dose beta-blocker had a five-fold increased risk of delivering a small-for-gestational-age infant compared with non-exposure (adjusted odds ratio [aOR] 4.89, 95% confidence interval [CI] 2.22–10.78, P < 0.001). Women using a low dose of beta-blocker had a two-fold increased risk of delivering a small-for-gestational-age infant; however, the confidence interval included the null (aOR 1.75, 95% CI 0.83–3.72, P = 0.143). Results when restricting the analyses to metoprolol showed the same pattern, but with attenuation of risks. We found a five-fold increased risk of delivering a small-for-gestational-age infant in women with heart disease treated with a high dose of beta-blocker, and a two-fold increased risk among those treated with a low dose, showing an apparent dose–response relation. Close monitoring of fetal growth is warranted among women with heart disease treated with beta-blockers. As drug therapy in pregnancy concerns both mother and fetus, an optimum balance for both should be the goal.