Search

Understanding the true burden of tobacco smoking on adverse pregnancy outcomes is critical in generating appropriate interventions to improve outcomes. Self-reporting of human behaviour that is associated with stigma is associated with underreporting in general and may bias the impact of smoking in studies; however, self-reporting is frequently the most practical method of gleaning this information. The objective of this study was to evaluate concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts. A total of 100 pregnant women (76 living with HIV [LWH] and 24 negative controls) in their third trimester, and 100 men and non-pregnant women (43 LWH and 57 negative controls) were included. Among all participants, 43 pregnant women (49% LWH and 25% negative controls) and 50 men and non-pregnant women (58% LWH and 44% negative controls) were self-reported smokers. The odds of discordance between self-reported smoking and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others, but were significantly increased, regardless of self-reported status, among people LWH compared to negative controls. The overall concordance between plasma cotinine and self-reported data among all participants was 94% with a sensitivity and specificity of 90% and 96%, respectively. Taken together, these data demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report smoking data among both persons LWH and not, including in the context of pregnancy., (© 2023. The Author(s).)

Background: In the randomized phase 3 VALOR-HCM study (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) of patients with obstructive hypertrophic cardiomyopathy, mavacamten reduced the need for septal reduction therapy. Because mavacamten improves ventricular compliance, this sub-study examined the effects of treatment with this cardiac myosin inhibitor on diastolic function., Methods: Symptomatic obstructive hypertrophic cardiomyopathy patients on maximally tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. At baseline and week 16, a resting and stress echocardiogram was performed with interpretation by a core laboratory. In this exploratory substudy, the principal end point was the change in parameters used to define the grade of diastolic function in patients treated with mavacamten and placebo. A related objective was to assess the proportion of patients with an improvement in diastolic function grade. A secondary aim was to assess for correlation between diastolic function parameters and the secondary end points from VALOR-HCM: New York Heart Association class, quality of life, and cardiac biomarkers., Results: Diastolic dysfunction grade was evaluable in 98 patients at baseline and week 16. Among patients treated with mavacamten, 29.4% (15 of 51) demonstrated improvement in diastolic function grade compared with 12.8% (6 of 47) patients with placebo ( P =0.05). Average E/e' ratio decreased significantly in patients treated with mavacamten (-3.4±5.3) compared with placebo (0.57±3.5; P <0.001). Indexed left atrial volumes (mL/m 2 ) also decreased significantly in patients who received mavacamten (-5.2±7.8) compared with placebo (-0.51±8.1; P =0.005). After adjustment for change in left ventricular outflow tract gradient and mitral regurgitation, mavacamten was significantly associated with a decrease in average E/e' ratio and indexed left atrial volumes. Change in average E/e' ratio was significantly correlated with the secondary end points from VALOR-HCM., Conclusions: In this exploratory substudy, after 16 weeks of therapy, mavacamten improved diastolic function, and this change correlated with improvement in clinical and biomarker end points., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04349072.

Cardiorespiratory fitness (as measured by peak oxygen consumption [VO 2peak ]) is an independent predictor of cardiovascular disease and all-cause mortality. Limited data exist on VO 2peak following repair for an acute type A aortic dissection (ATAAD) or proximal thoracic aortic aneurysm (pTAA). This study prospectively evaluated VO 2peak , functional capacity, and health-related quality of life (HR-QOL) following open repair. Participants with a history of an ATAAD (n = 21) or pTAA (n = 43) performed cardiopulmonary exercise testing (CPX), 6-minute walk testing, and HR-QOL at 3 (early) and 15 (late) months following open repair. The median age at time of surgery was 55-years-old and 60-years-old in the ATAAD and pTAA groups, respectively. Body mass index significantly increased between early and late timepoints for both ATAAD (p = 0.0245, 56% obese) and pTAA groups (p = 0.0045, 54% obese). VO 2peak modestly increased by 0.8 mLO2·kg-1·min-1 within the ATAAD group (p = 0.2312) while VO 2peak significantly increased by 2.2 mLO2·kg-1·min-1 within the pTAA group (p = 0.0003). Anxiety significantly decreased in the ATAAD group whereas functional capacity and HR-QOL metrics (social roles and activities, physical function) significantly improved in the pTAA group (p values < 0.05). There were no serious adverse events during CPX. Cardiorespiratory fitness among the ATAAD group remained 36% below predicted normative values >1 year after repair. CPX should be considered post-operatively to evaluate exercise tolerance and blood pressure response to determine whether mild-to-moderate aerobic exercise should be recommended to reduce future risk of morbidity and mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events., Methods and Results: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600)., Conclusions: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Variants in MYBPC3 causing loss of function are the most common cause of hypertrophic cardiomyopathy (HCM). However, a substantial number of patients carry missense variants of uncertain significance (VUS) in MYBPC3. We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will identify a subgroup of HCM patients with a MYBPC3 VUS associated with increased clinical risk., Methods: Among 7,963 patients in the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), 120 unique missense VUS in MYBPC3 were identified. Variants were evaluated for their effect on subdomain folding and a stratified time-to-event analysis for an overall composite endpoint (first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation, and stroke) was performed for patients with HCM and a MYBPC3 missense VUS., Results: We demonstrated that patients carrying a MYBPC3 VUS predicted to cause subdomain misfolding (STRUM+, ΔΔG ≤ -1.2 kcal/mol) exhibited a higher rate of adverse events compared with those with a STRUM- VUS (hazard ratio = 2.29, P = 0.0282). In silico saturation mutagenesis of MYBPC3 identified 4,943/23,427 (21%) missense variants that were predicted to cause subdomain misfolding., Conclusion: STRUM identifies patients with HCM and a MYBPC3 VUS who may be at higher clinical risk and provides supportive evidence for pathogenicity.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac condition and highly heterogeneous. Echocardiography and genetic and clinical screening have led to detection in women of childbearing age. Maternal and fetal outcomes among women with HCM are favorable. Genetic counseling is recommended. Prepregnancy clinical evaluation and risk assessment are paramount in ensuring optimal outcomes. Most women carry moderate risk of morbidity, have clinical evaluations and echocardiography each trimester, and deliver vaginally. Those who are symptomatic or have significant left ventricular outflow obstruction or recurrent arrhythmias prior to pregnancy are at higher risk and should be monitored at least monthly., Competing Interests: Disclosure The author has received honorarium and travel expense reimbursement for serving on an Advisory Board for MyoKardia, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder defined by left ventricular hypertrophy that cannot be explained by another cardiac or systemic disease. There is a general lack of knowledge about patients' perspectives on the symptoms and day-to-day limitations they experience as a result of HCM. We therefore sought an in-depth understanding of patients' experiences of obstructive (oHCM) and nonobstructive (nHCM) forms of the disease, including symptoms and their quality of life impacts, and to develop a conceptual model to capture them., Methods: Development of the HCM conceptual model involved a web-based survey to capture patients' insights, a targeted literature review (which included relevant guidelines and patient advocacy websites), one-to-one interviews with clinical experts, and one-to-one qualitative concept elicitation interviews with patients. Key symptoms and their impacts most important to patients' experiences were identified and used to develop a conceptual model of the patient experience with HCM., Results: The HCM symptoms reported by patient interviewees (n = 27) were largely consistent with findings from the patient web survey (n = 444), literature review, and interviews with three expert clinicians. The symptoms most commonly reported in patient interviews included tiredness (89%), shortness of breath (89%), shortness of breath with physical activity (89%), and dizziness/light-headedness (89%). Other symptoms commonly reported included chest pain (angina) (70%), chest pain (angina) with physical exertion (70%), and palpitations (fluttering or rapid heartbeat) (81%). The most commonly reported impacts of HCM symptoms on patients' lives included limitations to physical activities (78%), emotional impacts, including feeling anxious or depressed (78%), and impacts on work (63%). Symptoms and impacts were similar for both oHCM and nHCM., Conclusions: A conceptual model was developed, which identifies the core symptoms that patients with oHCM and nHCM reported as most frequent and most important: shortness of breath, palpitations, fatigue/tiredness, dizziness/light-headedness, and chest pain, as well as the impacts those symptoms have on patients' lives. This HCM conceptual model reflecting patients' experiences and perspectives was used in the development of a patient-reported outcomes instrument for use in clinical trials and it may also help inform the clinical management of HCM.

Purpose: There are limited data on cardiopulmonary exercise testing (CPX) and cardiorespiratory fitness (CRF), following open repair for a proximal thoracic aortic aneurysm or dissection. The aim was to evaluate serious adverse events, abnormal CPX event rate, CRF (peak oxygen uptake, (Equation is included in full-text article.)O2peak), and blood pressure., Methods: Patients were retrospectively identified from cardiac rehabilitation participation or prospectively enrolled in a research study and grouped by phenotype: (1) bicuspid aortic valve/thoracic aortic aneurysm, (2) tricuspid aortic valve/thoracic aortic aneurysm, and (3) acute type A aortic dissection., Results: Patients (n = 128) completed a CPX a median of 2.9 mo (interquartile range: 1.8, 3.5) following repair. No serious adverse events were reported, although 3 abnormal exercise tests (2% event rate) were observed. Eighty-one percent of CPX studies were considered peak effort (defined as respiratory exchange ratio of ≥1.05). Median measured (Equation is included in full-text article.)O2peak was <36% predicted normative values (19.2 mL·kgmin vs 29.3 mLkgmin, P < .0001); the most marked impairment in (Equation is included in full-text article.)O2peak was observed in the acute type A aortic dissection group (<40% normative values), which was significantly different from other groups (P < .05). Peak exercise systolic and diastolic blood pressures were 160 mm Hg (144, 172) and 70 mm Hg (62, 80), with no differences noted between groups., Conclusions: We observed no serious adverse events with an abnormal CPX event rate of only 2% 3 mo following repair for a proximal thoracic aortic aneurysm or dissection. (Equation is included in full-text article.)O2peak was reduced among all patient groups, especially the acute type A aortic dissection group, which may be clinically significant, given the well-established prognostic importance of reduced cardiorespiratory fitness.