Publications by authors named "Jolien W Roos-Hesselink"

330 Publications

Promising perspectives on pregnancy in women with congenital heart disease.

Eur Heart J 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab692DOI Listing
October 2021

Implantable loop recorders in patients with heart disease: comparison between patients with and without syncope.

Open Heart 2021 Aug;8(2)

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

Objective: Patients with heart disease are at increased risk for sudden cardiac death. Guidelines recommend an implantable loop recorder (ILR) for symptomatic patients when symptoms are sporadic and possibly arrhythmia-related. In clinical practice, an ILR is mainly used in patients with unexplained syncope. We aimed to compare the clinical value of an ILR in patients with heart disease and a history of syncope versus those with non-syncopal symptoms.

Methods: In this observational single-centre study, we included symptomatic patients with heart disease who received an ILR. The primary endpoint was an actionable event which was defined as an arrhythmic event leading to a change in clinical management. The secondary endpoint was an event leading to device implantation.

Results: One hundred and twenty patients (mean age 47±17 years, 49% men) were included. The underlying disease substrate was inherited cardiomyopathy (31%), congenital heart disease (28%), channelopathy (23%) and other (18%). Group A consisted of 43 patients with prior syncope and group B consisted of 77 patients with palpitations and/or near-syncope. The median follow-up duration was 19 months (IQR 8-36). The 3-year cumulative event rate was similar between groups with regard to the primary endpoint (38% vs 39% for group A and B, respectively, logrank p=0.54). There was also no difference in the 3-year cumulative rate of device implantation (21% vs 13% for group A and B, respectively, logrank p=0.65).

Conclusion: In symptomatic patients with heart disease, there is no difference in the yield of an ILR in patients presenting with or without syncope.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2021-001748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365783PMC
August 2021

Women of reproductive age in a tertiary intensive care unit: indications, outcome and the impact of pregnancy-a retrospective cohort study.

BMC Womens Health 2021 06 19;21(1):248. Epub 2021 Jun 19.

Department of Obstetrics and Gynecology, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: To evaluate the indications for admission and mortality rates of women of reproductive age admitted to a tertiary Intensive Care Unit (ICU) and to compare the outcomes of obstetric and non-obstetric admissions.

Methods: A retrospective cohort study was performed, including all women aged 17-41 years admitted to a level 3 ICU in the Netherlands, between January 1, 2000 and January 1, 2016. Primary outcome was indication for admission and mortality. Mortality, length of stay (LOS), need for mechanical ventilation and APACHE II score were compared between obstetric and non-obstetric admissions. The obstetric group was further analyzed for maternal and perinatal outcomes.

Results: 3461 women (median age 32 years) were included, with an overall mortality rate of 13.3%. The obstetric group consisted of 265 women (7.7%). The non-obstetric group (n = 3196) was admitted most often for cardiovascular disease (19.6%), followed by oncologic disease (15%). Mortality was the highest in women with oncologic disease (23.9%). The obstetric group had lower mortality compared to the non-obstetric group (4.9% vs. 14%, p < 0.001), despite higher APACHE II score (14 vs. 11, p < 0.001) and a higher ventilation rate (47.9% vs. 39%, p = 0.004). Major surgical or endovascular interventions, besides caesarean section, were performed in 46% of the obstetric group. Perinatal death occurred in 17.2% and of the surviving infants, 63.2% were born preterm and 45.1% required Neonatal Intensive Care Unit admission.

Conclusions: Cardiovascular disease is the most important indication for admission and oncologic disease is associated with highest mortality in women of reproductive age. Obstetric patients constitute a small percentage of all ICU admissions in a tertiary ICU center. They have lower mortality rates than non-obstetric young female patients, despite a more severe initial presentation. Nevertheless lasting maternal morbidity and perinatal mortality and morbidity is frequent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-021-01396-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214372PMC
June 2021

Letter to the Editor: "Incidence of atrial fibrillation in pregnancy and clinical significance: A meta-analysis".

Adv Med Sci 2021 May 29;66(2):269. Epub 2021 May 29.

Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.advms.2021.05.001DOI Listing
May 2021

Emergency department management of patients with adult congenital heart disease: a consensus paper from the ESC Working Group on Adult Congenital Heart Disease, the European Society for Emergency Medicine (EUSEM), the European Association for Cardio-Thoracic Surgery (EACTS), and the Association for Acute Cardiovascular Care (ACVC).

Eur Heart J 2021 07;42(26):2527-2535

DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.

Adult congenital heart disease (ACHD) patients represent a growing population with increasing use of acute emergency department (ED) care. Providing comprehensive ED care necessitates an understanding of the most common clinical scenarios to improve morbidity and mortality in this population. The aim of this position document is to provide a consensus regarding the management of the most common clinical scenarios of ACHD patients presenting to the ED.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab272DOI Listing
July 2021

Multi-plane echocardiographic assessment of right ventricular function in adults with repaired Tetralogy of Fallot.

Int J Cardiovasc Imaging 2021 Oct 18;37(10):2905-2915. Epub 2021 May 18.

Department of Cardiology, Erasmus MC Thorax Center, Rotterdam, The Netherlands.

In patients with repaired Tetralogy of Fallot (ToF), detailed assessment of right ventricular (RV) function is important for management and timing of possible pulmonary valve re-intervention. The aim of this study was to evaluate RV function using two-dimensional multi-plane echocardiography (2D MPE), a novel four-wall imaging method obtained from one apical acoustic window utilising electronic plane rotation. In sixty-two ToF patients (aged - 28 [22, 39] years, 65% male), systolic function of four different RV walls (lateral, anterior, inferior and inferior coronal) were evaluated using MPE. Tricuspid annular plane systolic excursion (TAPSE), tricuspid annular peak systolic velocity (RV-S') and RV wall longitudinal strain (RV-LS) measurements were compared with those of matched healthy individuals. 2D MPE measurements were highly feasible across the four RV walls (93.5-100% for TAPSE/S'; 66.1-95.1% for RVLS) and could be performed more reliably than 3D RV ejection fraction (RVEF - 56.5%). All functional values were significantly reduced when compared to the control group (p < 0.001). Higher RV-LS values were seen in the lateral (- 17.8 ± 4.5%) and inferior (- 17.8 ± 4.2%) walls compared to the anterior (- 15.9 ± 3.8%) and inferior coronal (- 15.1 ± 3.9%) walls. 3D RVEF correlated strongest with RV-LS values from the lateral (r - 0.50; p = 0.002) and anterior walls (r - 0.74; p < 0.001) and furthermore the four-wall average (r - 0.57; p = 0.001). 2D MPE evaluation of the RV is highly feasible in ToF patients. This novel method provides new insights into regional RV wall function, enabling a more comprehensive and quantitative approach to RV assessment in daily clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10554-021-02273-5DOI Listing
October 2021

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).

Heart 2021 Apr 28. Epub 2021 Apr 28.

Department of Cardiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

Objective: Cardiac disease is a major cause of maternal mortality. Data regarding pregnancy outcomes in women with a systemic right ventricle (sRV) are scarce. We studied pregnancy outcomes in women with an sRV after the atrial switch procedure for transposition of the great arteries (TGA) or congenitally corrected TGA (CCTGA).

Methods: The ESC EORP Registry of Pregnancy and Cardiac Disease is an international prospective registry of pregnant women with cardiac disease. Pregnancy outcomes (maternal/fetal) in all women with an sRV are described. The primary end point was a major adverse cardiac event (MACE) defined as maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischaemic coronary event and other thromboembolic events.

Results: Altogether, 162 women with an sRV (TGA n=121, CCTGA n=41, mean age 28.8±4.6 years) were included. No maternal mortality occurred. In 26 women, at least one MACE occurred, heart failure in 16 (9.8%), arrhythmias (atrial 5, ventricular 6) in 11 (6.7%) and others in 4 (2.5%). Prepregnancy signs of heart failure as well as an sRV ejection fraction <40% were predictors of MACE. One woman experienced fetal loss, while no neonatal mortality was observed. No significant differences were found between women with CCTGA and TGA. In the subset of women who had an echocardiogram before and after pregnancy, no clear deterioration in sRV was observed.

Conclusion: The majority of women with an sRV tolerated pregnancy well with a favourable maternal and fetal outcome. Heart failure and arrhythmias were the most common MACE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-318685DOI Listing
April 2021

Clinical outcome of anomalous coronary artery with interarterial course in adults: Single-center experience combined with a systematic review.

Int J Cardiol 2021 07 6;335:32-39. Epub 2021 Apr 6.

Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address:

Background: Anomalous coronary artery originating from the opposite sinus of Vasalva with interarterial course (ACAOS-IAC) is associated with sudden cardiac death (SCD) in young athletes. If identified in adulthood prognosis is usually more benign, resulting in a dilemma regarding revascularization.

Methods: This is a retrospective observational single-center study, including adults with ACAOS-IAC. Medical records between 2012 and 2019 were reviewed for management approach, mortality, cardiac death and coronary related adverse events. Coronary computed tomographic angiography (CCTA) were reviewed. We provide a literature review in regard to clinical outcome.

Results: We identified 40 patients with ACAOS-IAC (mean age 51). Presentation was acute in 7/40 (18%). Ischemia detection with single photon emission tomography (SPECT), cardiac magnetic resonance (CMR) or dobutamine stress echocardiography were performed in 25/40 (63%) patients. Ischemia in the vascular territory of the anomaly was present in 2/25 (8%). In 39/40 (98%) patients were treated expectative. During median follow-up of 2.7 years (IQR 1.5-5.3) no cardiovascular death was observed. Mortality occurred in 1/40 (3%) and coronary related adverse events in 2/40 (5%). We identified 20 studies describing 1194 patients. Revascularization was performed in 376/1154 (32.6%) patients. Mortality stratified for clinical management was 23/431 (5.3%) in the non-revascularization versus 16/253 (6.3%) in the revascularization group during 4.0 years follow-up (weighted median). Cause of death was cardiovascular in 10/596 (1.7%) in 4.2 years (weighted median) follow up.

Conclusions: Both revascularization and non-invasive management have good prognosis in adults with ACAOS-IAC during early follow up. There is need for guidelines and long-term surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.04.005DOI Listing
July 2021

Coronary aneurysm in a young patient with Turner syndrome.

Cardiol Young 2021 Jun 8;31(6):1019-1020. Epub 2021 Apr 8.

Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.

A young woman with Turner syndrome was found to have a large coronary aneurysm in the left anterior descending coronary artery upon CT angiogram screening for aortic pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951121001244DOI Listing
June 2021

Six-year serial follow-up with aortic 4D flow cardiovascular magnetic resonance in a patient with bicuspid aortic valve.

Eur Heart J Cardiovasc Imaging 2021 08;22(9):e144

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjci/jeab058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370564PMC
August 2021

Patient information portal for congenital aortic and pulmonary valve disease: a stepped-wedge cluster randomised trial.

Open Heart 2021 03;8(1)

Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted.

Methods: Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement.

Results: 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable.

Conclusion: Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2020-001252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993296PMC
March 2021

Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort.

J Am Heart Assoc 2021 02 24;10(5):e015022. Epub 2021 Feb 24.

Division of Pediatric Cardiology Department of Pediatrics Erasmus University Medical Center Rotterdam The Netherlands.

Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure. Methods and Results In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide), GDF-15 (growth differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after Fontan completion. After this baseline study measurement, follow-up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years, median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2 (4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT-proBNP was associated with (all) events during follow-up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe event-free survival was better in patients with low levels of GDF-15 (=0.005) and vWF (=0.008) and high levels of DLK-1 (=0.041). There was a positive correlation (β=0.33, =0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve. Conclusions NT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to long-term outcome in young patients who have undergone the Fontan procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.015022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174257PMC
February 2021

Incremental Value of an Insertable Cardiac Monitor in Patients with Hypertrophic Cardiomyopathy with Low or Intermediate Risk for Sudden Cardiac Death.

Cardiology 2021 21;146(2):207-212. Epub 2021 Jan 21.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands,

Aims: The aim of the present study was to compare the rate of actionable arrhythmic events between patients with hypertrophic cardiomyopathy (HCM) who are monitored with an insertable cardiac monitor (ICM) or Holter monitoring.

Methods: We studied 50 patients (mean age 52 years, 72% men) with HCM at low or intermediate risk for sudden cardiac death (SCD), of whom 25 patients received an ICM between November 2014 and February 2019. We retrospectively identified a control group of 25 patients who were matched on age, sex, and HCM Risk-SCD score category. The mean HCM Risk-SCD score was 3.41 ± 1.31 and 3.31 ± 1.43 for the ICM and Holter groups, respectively. The primary endpoint was an actionable event which was defined as an arrhythmic event resulting in a change in patient management. The secondary endpoint was the occurrence of ventricular tachycardia (VT).

Results: The cumulative actionable event rate at 30 months was higher in the ICM group (51 vs. 27%, log-rank p value <0.01). De novo atrial fibrillation requiring oral anticoagulation occurred only in the ICM group (n = 3). Overall, 4 implantable cardioverter-defibrillators were implanted for primary prevention (n = 2 in each group). The cumulative rate of VT episodes at 30 months was similar between groups (23% [ICM group] vs. 42% [Holter group], log-rank p value = 0.71). Furthermore, the characteristics of VT were similar between groups with regard to the number of beats and rate.

Conclusions: In adults with HCM, an ICM will detect more arrhythmic events requiring an intervention than a conventional Holter strategy. In contrast, the diagnostic yield of detecting VT seems similar for both groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117374PMC
August 2021

Pregnancy outcome in thoracic aortic disease data from the Registry Of Pregnancy And Cardiac disease.

Heart 2021 Nov 19;107(21):1704-1709. Epub 2021 Jan 19.

Cardiology Department, Erasmus Medical Center, Rotterdam, Netherlands

Background: Cardiovascular disease is the leading cause of death during pregnancy with thoracic aortic dissection being one of the main causes. Thoracic aortic disease is commonly related to hereditary disorders and congenital heart malformations such as bicuspid aortic valve (BAV). Pregnancy is considered a high risk period in women with underlying aortopathy.

Methods: The ESC EORP Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective global registry that enrolled 5739 women with pre-existing cardiac disease. With this analysis, we aim to study the maternal and fetal outcome of pregnancy in women with thoracic aortic disease.

Results: Thoracic aortic disease was reported in 189 women (3.3%). Half of them were patients with Marfan syndrome (MFS), 26% had a BAV, 8% Turner syndrome, 2% vascular Ehlers-Danlos syndrome and 11% had no underlying genetic defect or associated congenital heart defect. Aortic dilatation was reported in 58% of patients and 6% had a history of aortic dissection. Four patients, of whom three were patients with MFS, had an acute aortic dissection (three type A and one type B aortic dissection) without maternal or fetal mortality. No complications occurred in women with a history of aortic dissection. There was no significant difference in median fetal birth weight if treated with a beta-blocker or not (2960 g (2358-3390 g) vs 3270 g (2750-3570 g), p value 0.25).

Conclusion: This ancillary analysis provides the largest prospective data review on pregnancy risk for patients with thoracic aortic disease. Overall pregnancy outcomes in women with thoracic aortic disease followed according to current guidelines are good.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-318183DOI Listing
November 2021

Abnormal Aortic Wall Properties in Women with Turner Syndrome.

Aorta (Stamford) 2020 Oct 23;8(5):121-131. Epub 2020 Dec 23.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background:  Turner syndrome (TS) is associated with aortic dilatation and dissection, but the underlying process is unclear. The aim of this study was to investigate the elastic properties and composition of the aortic wall in women with TS.

Methods:  In this cross-sectional study, 52 women with TS aged 35 ± 13 years (50% monosomy, 12 with bicuspid aortic valve [BAV] and 4 with coarctation) were investigated using carotid-femoral pulse wave velocity (CF-PWV) by echocardiography and ascending aortic distensibility (AAD) and aortic arch pulse wave velocity (AA-PWV) by magnetic resonance imaging (MRI). As control group, 13 women with BAV without TS and 48 healthy patients were included.

Results:  Women with TS showed a higher AA-PWV (β = 1.08, confidence interval [CI]: 0.54-1.62) after correcting for age and comorbidities compared with controls. We found no significant difference in AAD and CF-PWV. In women with TS, the presence of BAV, coarctation of the aorta, or monosomy (45, X) was not associated with aortic stiffness. In addition, aortic tissue samples were investigated with routine and immunohistochemical stains in five additional women with TS who were operated. The tissue showed more compact smooth muscle cell layers with abnormal deposition and structure of elastin and diminished or absent expression of contractile proteins desmin, actin, and caldesmon, as well as the progesterone receptor.

Conclusion:  Both aortic arch stiffness measurements on MRI and histomorphological changes point toward an inherent abnormal thoracic aortic wall in women with TS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1714384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758113PMC
October 2020

Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme.

J Am Heart Assoc 2021 01 22;10(1):e018176. Epub 2020 Dec 22.

Department of Cardiology Erasmus University Medical Center Rotterdam the Netherlands.

Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.018176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955508PMC
January 2021

Imaging the adult with simple shunt lesions: position paper from the EACVI and the ESC WG on ACHD. Endorsed by AEPC (Association for European Paediatric and Congenital Cardiology).

Eur Heart J Cardiovasc Imaging 2021 05;22(6):e58-e70

Department of Adult Congenital Heart Disease, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK.

In 2018, the position paper 'Imaging the adult with congenital heart disease: a multimodality imaging approach' was published. The paper highlights, in the first part, the different imaging modalities applied in adult congenital heart disease patients. In the second part, these modalities are discussed more detailed for moderate to complex anatomical defects. Because of the length of the paper, simple lesions were not touched on. However, imaging modalities to use for simple shunt lesions are still poorly known. One is looking for structured recommendations on which they can rely when dealing with an (undiscovered) shunt lesion. This information is lacking for the initial diagnostic process, during repair and at follow-up. Therefore, this paper will focus on atrial septal defect, ventricular septal defect, and persistent arterial duct. Pre-, intra-, and post-procedural imaging techniques will be systematically discussed. This position paper will offer algorithms that might help at a glance. The document is prepared for general cardiologists, trainees, medical students, imagers/technicians to select the most appropriate imaging modality and to detect the requested information for each specific lesion. It might serve as reference to which researchers could refer when setting up a (imaging) study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjci/jeaa314DOI Listing
May 2021

Screening for coronary artery disease in early surgical treatment of acute aortic valve infective endocarditis.

Interact Cardiovasc Thorac Surg 2021 04;32(4):522-529

Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, Netherlands.

Objectives: In patients with unknown coronary status undergoing surgery for acute infective endocarditis (IE), the need to screen for coronary artery disease (CAD) and the risk of embolization during invasive coronary angiography (ICA) are debated. Coronary computed tomography angiography (CCTA) is a non-invasive alternative in these patients. We aimed to evaluate the safety and feasibility of ICA and CCTA to diagnose CAD, and the necessity to treat CAD to prevent CAD-related postoperative complications.

Methods: In this single-centre retrospective cohort study, all patients with acute aortic IE between 2009 and 2019 undergoing surgery were selected. Outcomes were any clinically evident embolization after preoperative ICA, in-hospital mortality, perioperative myocardial infarction or unplanned revascularization and postoperative renal function.

Results: Of the 159 included patients, CAD status was already known in 14. No preoperative diagnostics for CAD was done in 46/145, a CCTA was performed in 54/145 patients and an ICA in 52/145 patients. Significant CAD was found after CCTA in 22% and after ICA in 21% of patients. In 1 of the 52 (2%) patients undergoing preoperative ICA, a cerebral embolism occurred. The rate of perioperative myocardial infarction or unplanned revascularization in patients not screened for CAD was 2% (1 out of 46 patients).

Conclusions: Although the risk of embolism after preoperative ICA is low, it should be carefully weighed against the estimated risk of CAD-related perioperative complications. CCTA can serve as a gatekeeper for ICA in most patients with acute aortic IE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/icvts/ivaa313DOI Listing
April 2021

Tuning and External Validation of an Adult Congenital Heart Disease Risk Prediction Model.

Eur Heart J Qual Care Clin Outcomes 2020 Dec 12. Epub 2020 Dec 12.

Department of Cardiology, Erasmus University Medical Centre, Rotterdam, the Netherlands.

Aim: Adequate risk prediction can optimize the clinical management in adult congenital heart disease (ACHD). We aimed to update and subsequently validate a previously developed ACHD risk prediction model.

Methods And Results: A prediction model was developed in a prospective cohort study including 602 moderately or severely complex ACHD patients, enrolled as outpatients at a tertiary centre in the Netherlands (2011-2013). Multivariable Cox regression was used to develop a model for predicting the 1-year risks of death, heart failure, or arrhythmia (primary endpoint). The Boston ACHD Biobank study, a prospectively enrolled cohort (n = 749) of outpatients who visited a referral centre in Boston (2012-2017), was used for external validation. The primary endpoint occurred in 153 (26%) and 191 (28%) patients in the derivation and validation cohorts over median follow-up of 5.6 and 2.3 years, respectively. The final model included 5 out of 14 pre-specified predictors with the following HR's; NYHA class ≥II: 1.92 (95% CI 1.28-2.90), cardiac medication 2.52 (95% CI 1.72-3.69), ≥1 re-intervention after initial repair: 1.56 (95% CI 1.09-2.22), body mass index: 1.04 (95% CI 1.01-1.07), log2 NT-proBNP (pmol/L): 1.48 (95% CI 1.32-1.65). At external validation, the model showed good discrimination (C-statistic 0.79, 95% CI 0.74-0.83) and excellent calibration (calibration-in-the-large=-0.002; calibration slope = 0.99).

Conclusion: These data support the validity and applicability of a parsimonious ACHD risk model based on 5 readily available clinical variables to accurately predict the 1-year risk of death, heart failure or arrhythmia. This risk tool may help guide appropriate care for moderately or severely complex ACHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjqcco/qcaa090DOI Listing
December 2020

Transforming Growth Factor-β and the Renin-Angiotensin System in Syndromic Thoracic Aortic Aneurysms: Implications for Treatment.

Cardiovasc Drugs Ther 2020 Dec 7. Epub 2020 Dec 7.

Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Thoracic aortic aneurysms (TAAs) are permanent pathological dilatations of the thoracic aorta, which can lead to life-threatening complications, such as aortic dissection and rupture. TAAs frequently occur in a syndromic form in individuals with an underlying genetic predisposition, such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Increasing evidence supports an important role for transforming growth factor-β (TGF-β) and the renin-angiotensin system (RAS) in TAA pathology. Eventually, most patients with syndromic TAAs require surgical intervention, as the ability of present medical treatment to attenuate aneurysm growth is limited. Therefore, more effective medical treatment options are urgently needed. Numerous clinical trials investigated the therapeutic potential of angiotensin receptor blockers (ARBs) and β-blockers in patients suffering from syndromic TAAs. This review highlights the contribution of TGF-β signaling, RAS, and impaired mechanosensing abilities of aortic VSMCs in TAA formation. Furthermore, it critically discusses the most recent clinical evidence regarding the possible therapeutic benefit of ARBs and β-blockers in syndromic TAA patients and provides future research perspectives and therapeutic implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10557-020-07116-4DOI Listing
December 2020

Bleeding and thrombotic risk in pregnant women with Fontan physiology.

Heart 2021 Sep 24;107(17):1390-1397. Epub 2020 Nov 24.

Adult Congenital Heart Disease, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background/objectives: Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.

Methods: We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.

Results: We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096).

Conclusions: Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-317397DOI Listing
September 2021

Left ventricular strain values using 3D speckle-tracking echocardiography in healthy adults aged 20 to 72 years.

Int J Cardiovasc Imaging 2021 Apr 23;37(4):1189-1201. Epub 2020 Nov 23.

Department of Cardiology, Erasmus University Medical Center, Room Rg-433,'s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.

Three dimensional speckle tracking echocardiography (3D-STE) is a novel modality for the assessment of left ventricular strain (LVS). The aim of our study is to provide single vendor normative strain values measured with 3D-STE in healthy adult caucasians. One hundred fifty-five healthy subjects aged 20 to 72 years (≥ 28 subjects per decile) were prospectively included and examined with 2D and 3D transthoracic echocardiography. In 105 both 3D and 2D-STE were feasible (71%, mean age 44 ± 14 years, 51% female). Mean 3D tangential strain (3D-TS) was - 32 ± 2.9%. 3D global longitudinal strain (3D-GLS) demonstrated a significant but not very strong correlation with 2D-GLS values (- 19.7 ± 1.8% vs - 20.4 ± 2.2%, r = 0.462, p < 0.001). No gender difference was observed in 3D strain parameters. 3D-GLS decreased with increasing age stratum (p = 0.024). LVEF was associated with 3D-TS and 3D-GLS (r =  - 0.819, p ≤ 0.001 for 3D-TS, p =  - 0.477, r < 0.001, p = 0.001 for 3D-GLS). In this single vendor study age and gender-specific normative LV 3D-TS values were reported for healthy adult caucasians. In a significant proportion of the subjects 3D-STE was not feasible, but when feasible, 3D-STE shows excellent association with LVEF, and is therefore a promising novel modality for the assessment of the myocardial function, provided that issues of limited feasibility and temporal resolution are addressed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10554-020-02100-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026477PMC
April 2021

Influence of Pregnancy on Aortic Diameter in Women With the Turner Syndrome.

Am J Cardiol 2021 02 2;140:122-127. Epub 2020 Nov 2.

Department of Cardiology, Erasmus Medical Centre, Rotterdam, the Netherlands.

Women with Turner syndrome (TS) have high prevalence of cardiovascular anomalies. Literature suggests pregnancy is associated with a higher dissection risk, presumably preceded by aortic dilatation. Whether the aortic diameter truly changes during pregnancy in TS is not well investigated. This study aims to evaluate ascending aortic diameter change during pregnancy and reports on cardiac events during and directly after pregnancy. This tertiary hospital retrospective study investigated all TS women pregnancies (2009 to 2018). Outcome parameters included aortic diameter growth and aortic complications, specifically dissection. Thirty-five pregnancies in 30 TS women, 57% assisted by oocyte donation. Mean age at delivery 32 ± 5 years. In 27 pregnancies of 22 women imaging was available. From over 350 childless TS women a comparison group of 27 was individually matched. The median ascending aortic diameter growth between pre- and postpregnancy imaging was 1.0 mm (IQR -1.0; 2.0), no significant change (p = 0.077). Whether the patient had a bicuspid aortic valve (p = 0.571), monosomy X or mosaic karyotype (p = 0.071) or spontaneous pregnancy or resulting from oocyte donation (p = 0.686) had no significant influence on diameter change. Aortic growth between pregnancy and matched childless group (0.23 vs 0.32 mm/year, p = 0.788) was not significant over 3.3 ± 2 versus 4.4 ± 1 years. During pregnancy or the first 6 months after delivery no aortic complications were observed. In conclusion, this study suggests pregnancy in TS women does not induce faster ascending aortic diameter increase. Also not in presence of a bicuspid aortic valve, monosomy X karyotype, and oocyte donation. No aortic complications occurred. Based on current study pregnancy in TS women seems safe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2020.10.047DOI Listing
February 2021

European Society of Cardiology Working Group on Adult Congenital Heart Disease and Study Group for Adult Congenital Heart Care in Central and South Eastern European Countries consensus paper: current status, provision gaps and investment required.

Eur J Heart Fail 2021 03 19;23(3):445-453. Epub 2020 Nov 19.

Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK.

Aims: To examine the current status of care and needs of adult congenital heart disease (ACHD) services in the Central and South Eastern European (CESEE) region.

Methods And Results: We obtained data regarding the national ACHD status for 19 CESEE countries from their ACHD representative based on an extensive survey for 2017 and/or 2018. Thirteen countries reported at least one tertiary ACHD centre with a median year of centre establishment in 2007 (interquartile range 2002-2013). ACHD centres reported a median of 2114 patients under active follow-up with an annual cardiac catheter and surgical intervention volume of 49 and 40, respectively. The majority (90%) of catheter or surgical interventions were funded by government reimbursement schemes. However, all 19 countries had financial caps on a hospital level, leading to patient waiting lists and restrictions in the number of procedures that can be performed. The median number of ACHD specialists per country was 3. The majority of centres (75%) did not have ACHD specialist nurses. The six countries with no dedicated ACHD centres had lower Gross Domestic Product per capita compared to the remainder (P = 0.005).

Conclusion: The majority of countries in CESEE now have established ACHD services with adequate infrastructure and a patient workload comparable to the rest of Europe, but important gaps still exist. ACHD care is challenged or compromised by limited financial resources, insufficient staffing levels, and reimbursement caps on essential procedures compared to Western Europe. Active advocacy and increased resources are required to address the inequalities of care across the continent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2040DOI Listing
March 2021

Pregnancy outcomes in women with aortic coarctation.

Heart 2020 Oct 29. Epub 2020 Oct 29.

Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands

Objective: Pregnancy in women with aortic coarctation (CoA) has an estimated moderately increased risk (mWHO II-III) of adverse cardiovascular, obstetric or fetal events, but prospective data to validate this risk classification are scarce. We examined pregnancy outcomes and identified associations with adverse outcomes.

Methods: Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=303 out of 5739), part of the European Society of Cardiology EURObservational Research Programme. The frequency of and associations with major adverse cardiac events (MACE) and hypertensive disorders (pregnancy-induced hypertension, (pre-)eclampsia or haemolysis, elevated liver enzymes and low platelets syndrome) were analysed.

Results: Of 303 pregnancies (mean age 30 years, pregnancy duration 39 weeks), 9.6% involved unrepaired CoA and 27.1% were in women with pre-existing hypertension. No maternal deaths or aortic dissections occurred. MACE occurred in 13 pregnancies (4.3%), of which 10 cases were of heart failure (3.3%). Univariable associations with MACE included prepregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8 to 147.7), left ventricular ejection fraction <40% (OR 10.4, 95% CI 1.8 to 59.5), New York Heart Association class >1 (OR 11.4, 95% CI 3.6 to 36.3) and cardiac medication use (OR 4.9, 95% CI 1.3 to 18.3). Hypertensive disorders of pregnancy occurred in 16 (5.3%), cardiac medication use being their only predictor (OR 3.2, 95% CI 1.1 to 9.6). Premature births were 9.1%, caesarean section was performed in 49.7% of pregnancies. Of 4 neonatal deaths, 3 were after spontaneous extreme preterm birth.

Conclusions: The ROPAC data show low MACE and hypertensive disorder rates during pregnancy in women with CoA, suggesting pregnancy to be more safe and better tolerated than previously appreciated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-317513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873427PMC
October 2020

Prognostic value of C-reactive protein in adults with congenital heart disease.

Heart 2020 Oct 15. Epub 2020 Oct 15.

Cardiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: High-sensitivity C reactive protein (hs-CRP) has been associated with outcomes in adult congenital heart disease (ACHD). However, its prognostic value beyond N-terminal pro B type natriuretic peptide (NT-proBNP) or troponin T remains unknown. We studied the temporal evolution of hs-CRP, as well as the relation between hs-CRP and adverse clinical outcomes independent of NT-proBNP and troponin T in patients with ACHD.

Methods: In this prospective cohort study, we enrolled 602 patients with ACHD (2011-2013) who underwent baseline and thereafter annual blood sampling during 4 years. Hs-CRP, hs-troponin T and NT-proBNP were measured. The primary endpoint was composed of death or heart failure (HF). Cox regression and Joint Modelling was used to relate 2log hs-CRP levels with the endpoint, with adjustment for baseline characteristics and (repeated) hs-troponin T and NT-proBNP measurements.

Results: Hs-CRP was measured at baseline in 591 patients, median age 33 years, 58% men, 90% New York Heart Association I with an average of 4.3 measurements per patient. Median follow-up was 5.9 (IQR 5.3-6.3) years (99.2% complete) and 69 patients met the endpoint. Higher baseline hs-CRP was independently associated with higher risk of death or HF (HR 1.36, 95% CI 1.19 to 1.55). Hs-CRP increased over time prior to death or HF, and repeated hs-CRP measurements were associated with the endpoint, independent of repeated NT-proBNP and hs-troponin T (HR 1.54, 95% CI 1.24 to 1.98).

Conclusions: Hs-CRP carries incremental prognostic value for the risk of death or HF, beyond NT-proBNP and hs-troponin T. Hs-CRP increased prior to the occurrence of HF or death, supporting the role of inflammation in the clinical deterioration of patients with ACHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-316813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925816PMC
October 2020

Health-related quality of life and lived experiences in males and females with thoracic aortic disease and their partners.

Open Heart 2020 10;7(2)

Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands

Objective: Thoracic aortic disease (TAD) may have substantial impact on health-related quality of life (HRQOL). We described HRQOL in patients with TAD, cardiovascular screening participants and their partners; identified factors associated with HRQOL; and explored lived experiences and feelings of anxiety or depression using a mixed methods design.

Methods: For this cross-sectional study, all consecutive patients visiting the TAD outpatient clinic (2017-2019) at our centre were asked to complete three questionnaires: the Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HADS) and the Rotterdam Disease Specific Questionnaire (RDSQ). A subsample was invited for in-depth interviews.

Results: In total, 261 participants were included: 147 patients with TAD (thoracic aortic diameter ≥40 mm; 54 females, 36.7%), 114 screening participants (cardiovascular family screening; 71 females, 62.3%) and 66 partners. Compared with the general population, patients with TAD showed markedly lower HRQOL, whereas screening participants' HRQOL was less impaired. Female and younger participants scored significantly lower on the SF-36 and HADS compared with male and older participants. Smaller aortic diameter was associated with better RDSQ score, and previous aortic surgery was associated with higher HADS depression scores. Furthermore, partners scored significantly lower on 2/8 SF-36 subdomains when compared with the general population. From 11 interviewees, determinants of psychological distress included coping strategies, impact on social and professional life, disease-related knowledge, state of aortic diameters and physical symptoms.

Conclusions: Healthcare professionals must be aware of HRQOL impairments in patients with TAD, particularly in younger females. Moreover, attention for partners is needed. Coping strategies and communication within the family were found to be important factors influencing psychological distress, and might be valuable leads for counselling and HRQOL improvement in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2020-001419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545641PMC
October 2020

Repetitive out of hospital cardiac arrests following pregnancy: a case report of an unfortunate presentation of mitral annular disjunction.

Eur Heart J Case Rep 2020 Aug 26;4(4):1-7. Epub 2020 May 26.

Department of Cardiology, Erasmus Medical Centre, Congenital heart disease RG4, PO Box 2040, 3000 CA, Rotterdam, the Netherlands.

Background: Mitral annular disjunction (MAD) is an under-recognized cause of arrhythmic sudden cardiac death, especially in young women. The relation between MAD and the occurrence of arrhythmia during pregnancy has not yet been explored. We would like to stress the importance of careful echocardiographic examination and the vulnerable peripartum period.

Case Summary: A 29-year-old woman survived an out of hospital cardiac arrest 4 months after delivery of her first child. The diagnosis was not clear and an implantable cardioverter-defibrillator (ICD) as secondary prevention was implanted. Her second pregnancy and delivery were uneventful. The 12-lead electrocardiogram demonstrated sinus rhythm with right bundle branch block, ventricular extra systoles (premature ventricular contractions), and a right superior axis, i.e. origin in the inferolateral basal left ventricle. Transthoracic 2D echocardiography showed myxomatous mitral valve disease with moderate mitral valve insufficiency with normal left and right heart dimensions and function. However, 4 weeks after delivery she experienced a sudden syncope at home. Implantable cardioverter-defibrillator reading revealed primary ventricular fibrillation, induced by a ventricular premature beat (VPB), terminated with a successful ICD shock. A frame-by-frame echocardiographic analysis of the mitral valve using biplane echocardiographic analysis allowed diagnosis of MAD with detachment of the root of the annulus from the posterolateral ventricular myocardium during systole.

Conclusion: Mitral annular disjunction is an under-recognized cause of arrhythmic sudden cardiac death. Biplane echocardiographic analysis of the mitral annulus can identify MAD and as such may help for risk stratification and sudden cardiac death prevention. Careful follow-up is necessary especially during pregnancy and the postpartum period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjcr/ytaa135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501944PMC
August 2020
-->