Pregnancy related changes in Doppler gradients and left ventricular mechanics in women with sub-valvular or valvular aortic stenosis.

BACKGROUND: The aim of our study was to characterize echocardiographic changes during pregnancy in women with known LVOT obstruction or AS compared to the healthy pregnancy controls, and to assess the relationship with pregnancy outcomes. METHODS: We retrospectively studied 34 pregnant patients with congenital LVOT obstruction or AS with healthy age-matched pregnant controls. Patients with other significant valvular lesions, structural heart disease (LVEF < 40%), or prior valve surgery were excluded. All LVOTO/AS patients underwent a minimum of two consecutive echocardiograms between 1 year pre-conception and 1 year postpartum, with at least two studies during the pregnancy. Comprehensive echocardiographic evaluation was performed including speckle-tracking LV global longitudinal strain. RESULTS: A total of 83 echocardiograms from the study group and 34 echocardiograms from the control group were evaluated. Over the range of LVOTO/AS, a significantly greater increase in the AV gradients and LV and LA volumes were observed as compared with the controls. In the sub-group of LVOTO/AS pregnant women with ≥ moderate (n = 8) versus < moderate LVOTO/AS (n = 26), averaged 2nd /3rd trimester LVEF was lower (51 ± 12)% versus (58 ± 4)%, (p = 0.02) and GLS was lower (-19.5 ± 2.8) versus (21.2 ± 2.4), (p = 0.06). Pregnancy was well tolerated despite these changes. CONCLUSION: Among pregnant women with even milder forms of LVOTO/AS, increases in cardiac volumes and AV gradients can be expected over the course of pregnancy. Significant decreases in LV function and mechanics were only observed in women with moderate or greater LVOTO/AS, although still remained in normal range.

Changes to the electrocardiogram during exercise in anorexia nervosa.

BACKGROUND: Anorexia Nervosa (AN) is an eating disorder characterized by low body weight, distorted body image, and an intense fear of gaining weight. Electrocardiogram (ECG) changes, particularly in the QT interval, have been implicated in AN-associated sudden death but not well defined. OBJECTIVES: To characterize QT interval changes during exercise in anorexia nervosa. METHODS: The QT interval was evaluated in a prospective cohort undergoing structured exercise. Patients from the St. Paul's Hospital Provincial Adult Tertiary Eating Disorders Program underwent a 6-minute modified exercise test protocol. A single lead ECG patch recording device was used to record a Lead I equivalent, due to challenges applying standard ECG monitoring in subjects with low body mass. Heart rate (HR) and QT interval were assessed. RESULTS: Eighteen eating disorder patients (16 female) completed testing (age 31 ± 12 years, BMI 16.5 ± 3.8 kg/m2). Patients were compared to age- and sex-matched healthy controls. HR was similar between patients and controls (baseline: 65 (55-70)bpm vs. 69 (53-73)bpm, p = 0.83; maximum: 110 (94-139) bpm vs. 108 (93-141) bpm, p = 0.96; end recovery: 62 (54-68) bpm vs. 66 (55-75) bpm, p = 0.39). QTc intervals were similar between groups at baseline (381 ± 17 ms vs. 381 ± 46 ms, p = 0.93) and end recovery (397 ± 42 ms vs 398 ± 42 ms, p = 0.91). However, AN patients demonstrated QTc prolongation while controls showed QTc shortening at maximum HR (426 ± 70 ms vs. 345 ± 59 ms, p = 0.001). CONCLUSION: Low level exercise HR increases are similar between AN patients and controls, but the QTc interval fails to shorten, which may explain the increased arrhythmic risk in AN.

Changes on the electrocardiogram in anorexia nervosa: A case control study.

PURPOSE: Anorexia nervosa is a complex psychiatric condition with increased mortality. The electrocardiogram (ECG) may show repolarization changes which may associate with an increased risk of sudden death. Up to 80% of patients may be prescribed psychopharmacotherapies which alter the ECG, potentially compounding arrhythmic risk. This study aimed to describe and improve understanding of ECG changes in eating disorders and assess the effect of psychopharmacotherapies. METHODS: Adolescent patients diagnosed with anorexia nervosa were reviewed. ECGs were reviewed by blinded expert reviewers, and repolarization parameters were compared to healthy controls. Patients on and off psychopharmacotherapies were compared. RESULTS: Thirty-eight anorexia nervosa patients off psychopharmacotherapies were age matched to 53 healthy controls. Heart rate was lower in anorexia nervosa patients (56 vs. 74 bpm, p < 0.001). The absolute QT interval was longer in patients compared to controls (408 vs. 383 ms, p < 0.001), but the QTc by Hodges' formula was similar between groups (401 vs. 408 ms, p = 0.16). The prevalence of T-wave flattening and inversion was also similar between groups (13% vs. 4%, p = 0.12) and T-peak to T-end interval (Tpe) was shorter in patients compared to controls (p < 0.01). ECG parameters were similar between patients on and off psychopharmacotherapies aside from off-drug patients showing lower HR (56 vs. 65, p = 0.04). CONCLUSIONS: Autonomic and repolarization changes are evident on the ECG of anorexia nervosa patients, though the QTc interval was in fact similar between groups. Changes in T-wave morphology and duration may be promising metrics of repolarization effects of anorexia nervosa.

Management of Inherited Arrhythmia Syndromes: A HiRO Consensus Handbook on Process of Care.

Inherited arrhythmia syndromes are rare genetic conditions that predispose seemingly healthy individuals to sudden cardiac arrest and death. The Hearts in Rhythm Organization is a multidisciplinary Canadian network of clinicians, researchers, patients, and families that aims to improve care for patients and families with inherited cardiac conditions, focused on those that confer predisposition to arrhythmia and sudden cardiac arrest and/or death. The field is rapidly evolving as research discoveries increase. A streamlined, practical guide for providers to diagnose and follow pediatric and adult patients with inherited cardiac conditions represents a useful tool to improve health system utilization, clinical management, and research related to these conditions. This review provides consensus care pathways for 7 conditions, including the 4 most common inherited cardiac conditions that confer predisposition to arrhythmia, with scenarios to guide investigation, diagnosis, risk stratification, and management. These conditions include Brugada syndrome, long QT syndrome, arrhythmogenic right ventricular cardiomyopathy and related arrhythmogenic cardiomyopathies, and catecholaminergic polymorphic ventricular tachycardia. In addition, an approach to investigating and managing sudden cardiac arrest, sudden unexpected death, and first-degree family members of affected individuals is provided. Referral to specialized cardiogenetic clinics should be considered in most cases. The intention of this review is to offer a framework for the process of care that is useful for both experts and nonexperts, and related allied disciplines such as hospital management, diagnostic services, coroners, and pathologists, in order to provide high-quality, multidisciplinary, standardized care.

Les syndromes d'arythmie héréditaires sont des troubles génétiques rares qui prédisposent des personnes en apparence en bonne santé à un arrêt cardiaque soudain et à la mort. L'organisation Hearts in Rhythm Organization est un réseau multidisciplinaire canadien qui regroupe des cliniciens, des chercheurs ainsi que des patients et leurs proches dans le but d'améliorer les soins prodigués aux patients atteints de maladies cardiaques héréditaires et à leur famille, en particulier dans le cas des maladies qui entraînent une prédisposition à l'arythmie et à un arrêt cardiaque soudain et/ou à la mort. Puisque ce champ de recherche évolue rapidement, la mise au point d'un guide pratique et simple à l'intention des professionnels de la santé pour le diagnostic et le suivi des patients enfants et adultes présentant une maladie cardiaque héréditaire serait donc un outil intéressant pour améliorer l'utilisation du système de santé et la prise en charge clinique de ces maladies tout en orientant la recherche à ce propos. La présente synthèse expose les trajectoires de soins faisant l'objet d'un consensus pour sept maladies, dont les quatre maladies cardiaques héréditaires les plus courantes qui prédisposent à l'arythmie. Elle présente aussi des scénarios pour orienter les examens, le diagnostic, la stratification du risque et la prise en charge des patients. Ces maladies sont le syndrome de Brugada, le syndrome du QT long, la cardiomyopathie arythmogénique du ventricule droit et les cardiomyopathies arythmogènes associées, et la tachycardie ventriculaire polymorphe catécholaminergique. En outre, une approche pour la prise en charge de l'arrêt cardiaque soudain, de mort subite inattendue et des membres de la famille immédiate de la personne touchée est proposée. L'orientation vers des cliniques spécialisées en cardiogénétique doit être envisagée dans la plupart des cas. L'objectif est d'établir un cadre de soins qui soit utile pour les experts et les non-experts ainsi que pour les professionnels des domaines connexes, par exemple le personnel de l'administration hospitalière et des services diagnostiques, les coroners et les pathologistes, en vue d'offrir des soins multidisciplinaires normalisés de grande qualité.

Two-Dimensional Strain Echocardiographic Parameters and Clinical Outcomes Associated with Significant Atrioventricular Regurgitation in a Single-Center Adult Fontan Population.

Background: Significant atrioventricular valve regurgitation (AVVR) is prevalent in Fontan adults. Two-dimensional speckle-tracking echocardiography allows for evaluation of subclinical myocardial dysfunction and offers technical benefits. We aimed to evaluate the association of AVVR with echocardiographic parameters and adverse outcomes. Materials and Methods: Fontan adults (≥18 years) with lateral tunnel or extracardiac connection actively followed at our institution were retrospectively reviewed. Patients with AVVR on most recent transthoracic echocardiogram (≥grade 2 as per American Society of Echocardiography guidelines) were matched with Fontan controls. Echocardiographic parameters, including global longitudinal strain (GLS), were measured. The composite outcome of Fontan failure included Fontan conversion, protein losing enteropathy, plastic bronchitis, and New York Heart Association Class III/IV. Results: Sixteen patients (14%, mean age 28.4 ± 7.0 years) with predominantly moderate AVVR (81%) were identified. The mean duration of AVVR was 8.1 ± 5.8 months. There was no significant reduction in ejection fraction (EF) (51.2% ± 11.7% vs. 54.7% ± 10.9%, P = 0.39) or GLS (-16.0% ± 5.2% vs. -16.0% ± 3.5%, P = 0.98) associated with AVVR. Larger atrial volumes and longer deceleration time (DT) were observed in the AVVR group. Patients with AVVR and a worse GLS (≥-16%) had higher E velocity, DT, and medial E/E' ratio. The incidence of Fontan failure did not differ from controls (38% vs. 25%, P = 0.45). Patients with worse GLS (≥-16%) demonstrated a marked trend toward a higher incidence of Fontan failure (67% vs. 20%, P = 0.09). Conclusions: In Fontan adults, a short duration of AVVR did not influence EF or GLS but was associated with larger atrial volumes and those with worse GLS demonstrated some differences in diastolic parameters. Larger multicenter studies throughout its disease course are warranted.

Psychological Distress in Adults With Congenital Heart Disease Over the COVID-19 Pandemic.

Background This study sought to better understand the experiences of adults with congenital heart disease throughout the pandemic. Objectives were to determine (1) psychological distress before and throughout the pandemic; (2) changes in day-to-day functioning; and (3) the percentage of adults with congenital heart disease who experienced COVID-19 related symptoms, underwent testing, and tested positive. Methods and Results This was a cross-sectional study paired with retrospective chart review. A web-based survey was distributed to patients between December 2020 and January 2021. Patients reported on psychological distress across 5 categories (Screening Tool for Psychological Distress; depression, anxiety, stress, anger, and lack of social support), whether they experienced symptoms of COVID-19 and/or sought testing, and changes to their work and social behavior. Five hundred seventy-nine survey responses were received, of which 555 were linked to clinical data. Patients were aged 45±15 years. The proportion of patients reporting above-threshold values for all Screening Tool for Psychological Distress items significantly increased during the early pandemic compared with before the pandemic. Stress returned to baseline in December 2020/January 2021, whereas all others remained elevated. Psychological distress decreased with age, and women reported persistently elevated stress and anxiety compared with men during the pandemic. A consistent trend was not observed with regard to American College of Cardiology/American Heart Association anatomic and physiologic classification. Fifty (9%) patients lost employment because of a COVID-19-related reason. COVID-19 symptoms were reported by 145 (25%) patients, 182 (31%) sought testing, and 10 (2%) tested positive. Conclusions A substantial proportion of adults with congenital heart disease reported clinically significant psychological distress during the pandemic.

Trending Cardiac Biomarkers During Pregnancy in Women With Cardiovascular Disease.

BACKGROUND: Clinical utility of cardiac biomarker testing during pregnancy in women with preexisting cardiac disease is not well known. We studied the levels and temporal trends of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-cTnI (high-sensitivity cardiac troponin I) throughout pregnancy in women with preexisting cardiac disease and sought to assess the association between NT-proBNP and hs-cTnI and pregnancy outcomes. METHODS: Three hundred seven pregnant women with preexisting cardiac disease were prospectively recruited. Mixed-effects linear regression analysis was used to compare the NT-proBNP and hs-cTnI levels between time periods and subgroups. Logistic regression analysis adjusted for maternal age and CARPREG II (Cardiac Disease in Pregnancy) risk score assessed the association between NT-proBNP levels and adverse events. RESULTS: Geometric mean NT-proBNP (95% CI) was stable through pregnancy with a transient significant increase with labor and delivery (101.4 pg/mL [87.1-118.1], 90.2 pg/mL [78.5-103.6], 153.6 pg/mL [126.8-186.1], and 112.2 pg/mL [94.2-133.7] for first/second trimester, third trimester, labor/delivery and postpartum, respectively). We observed a statistically significant difference in the NT-proBNP between women with preserved versus decreased systemic ventricular function, structurally normal versus abnormal heart, modified World Health Organization class 1, 2 versus modified World Health Organization class 3, 4 and no congenital heart disease versus congenital heart disease. Compared to those without events, median (interquartile range) NT-proBNP levels were significantly higher in those who had heart failure (204 pg/mL [51-450] versus 55 pg/mL [31-97]; P=0.001) and preeclampsia (98 pg/mL [40-319] versus 55 pg/mL [31-99]; P=0.027). NT-proBNP, adjusted for age and CARPREG II risk score, was significantly associated with combined heart failure and preeclampsia (adjusted odds ratio, 2.14 [95% CI, 1.48-3.10] per log NT-proBNP increase; P<0.001). NT-proBNP <200 pg/mL had a specificity of 91% and negative predictive value of 95% in predicting combined heart failure and preeclampsia. CONCLUSIONS: NT-proBNP remains steady over the course of pregnancy with a transient increase during labor and delivery with higher levels in subgroups of stable cardiac patients. NT-proBNP level of 200 pg/mL can be used in the diagnosis of heart failure/preeclampsia in the pregnant cardiac population.

Cost Analysis of Patients Referred for Inherited Heart Rhythm Disorder Evaluation.

BACKGROUND: Inherited heart rhythm disorders (IHRDs) are complex and uncommon arrhythmogenic conditions that can lead to sudden unexpected death in seemingly healthy individuals. Multidisciplinary programs can assist in the diagnostic testing of potentially affected individuals and their family members. METHODS: Patients evaluated in a specialized adult and pediatric IHRD clinic between April 2013 and February 2015 were characterized. The total costs per evaluation and diagnosis were calculated. Patients were divided according to referral indication (primary referral or family member). RESULTS: A total of 618 patients were evaluated (age 36 ± 21 years; 52% male), of which 274 (44%) were primary referrals and 344 (56%) were family members referred for cascade screening. Overall, 47% had at least 1 follow-up visit. Patients had a median of 3 tests; primary referrals required more tests (4 vs 2; P < 0.01). The median cost per patient was $1340 CAD. Evaluation of the primary referrals was costlier than family members ($3096 vs $983; P < 0.01). A definite or probable diagnosis was determined in 464 patients (77%), with no difference according to patient type (P = 0.18). The total cost per diagnosis was $4021 in primary referrals compared with $1277 in family members (P < 0.01). CONCLUSIONS: Clinical evaluation of patients with suspected IHRD results in a high diagnostic yield and costs aligned with other complex disorders involving multidisciplinary clinics. Evaluation costs are expectedly higher in primary referrals compared with targeted family screening.

Cardiac Abnormalities in First-Degree Relatives of Unexplained Cardiac Arrest Victims: A Report From the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry.

BACKGROUND: Unexplained cardiac arrest (UCA) may be explained by inherited arrhythmia syndromes. The Cardiac Arrest Survivors With Preserved Ejection Fraction Registry prospectively assessed first-degree relatives of UCA or sudden unexplained death victims to screen for cardiac abnormalities. METHODS AND RESULTS: Around 398 first-degree family members (186 UCA, 212 sudden unexplained death victims' relatives; mean age, 44±17 years) underwent extensive cardiac workup, including ECG, signal averaged ECG, exercise testing, cardiac imaging, Holter-monitoring, and selective provocative drug testing with epinephrine or procainamide. Genetic testing was performed when a mutation was identified in the UCA survivor or when the diagnostic workup revealed a phenotype suggestive of a specific inherited arrhythmia syndrome. The diagnostic strength was classified as definite, probable, or possible based on previously published definitions. Cardiac abnormalities were detected in 120 of 398 patients (30.2%) with 67 of 398 having a definite or probable diagnosis (17%), including Long-QT syndrome (13%), catecholaminergic polymorphic ventricular tachycardia (4%), arrhythmogenic right ventricular cardiomyopathy (4%), and Brugada syndrome (3%). The detection yield was similar for family members of UCA and sudden unexplained death victims (31% versus 27%; P=0.59). Genetic testing was performed more often in family members of UCA patients (29% versus 20%; P=0.03). Disease-causing mutations were identified in 20 of 398 relatives (5%). The most common pathogenic mutations were RyR2 (2%), SCN5A (1%), and KNCQ1 (0.8%). CONCLUSIONS: Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.

Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry.

BACKGROUND: The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent. METHODS AND RESULTS: The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.6±14.7 years, 41% female). Patients were free of evidence of coronary artery disease, left ventricular dysfunction, or evident repolarization syndromes. Advanced testing determined a diagnosis in 34% of patients at baseline, with a diagnosis emerging during follow-up in 7% of patients. Of those who were diagnosed, 28 (35%) had an underlying structural condition and 53 (65%) had a primary electric disease. During a mean follow-up of 3.15±2.34 years, 23% of patients had either a shock or an appropriate antitachycardia pacing from their implantable cardioverter defibrillator, or both. The implantable cardioverter defibrillator appropriate intervention rate was 8.4% at 1 year and 18.1% at 3 years, with no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a primary electric versus structural pathogenesis. CONCLUSIONS: Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate implantable cardioverter defibrillator therapy during medium-term follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032.