Metabolic-associated fatty liver disease is characterized by a post-oral glucose load hyperinsulinemia in individuals with mild metabolic alterations.

Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5-6.9 mmol/L, or glycated hemoglobin 5.7-5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic ß-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45-65) vs. 57 (44-63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (P < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic ß-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (P < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase ß-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D.NEW & NOTEWORTHY Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic ß-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes.

The Canadian Cardiovascular Society Classification of Acute Atherothrombotic Myocardial Infarction Based on Stages of Tissue Injury Severity: An Expert Consensus Statement.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.

Lay summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms. Aim/hypothesis: Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes. Methods: A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL). Results: Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001). Conclusion: In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

Associations of insulin-like growth factor binding protein-2 with metabolic profile and hepatic fat deposition in asymptomatic men and women.

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women. Three hundred thirty-three middle-aged Caucasian men and women apparently healthy and without cardiovascular symptoms were enrolled for a cross-sectional cardiometabolic imaging study. Individuals with BMI ≥ 40 kg/m2, cardiovascular disease, dyslipidemia, hypertension, and diabetes were excluded. Fasting glucose and lipid profiles were measured and an oral glucose tolerance test was performed. Liver fat content was assessed by magnetic resonance spectroscopy. Volume of visceral adipose tissue (VAT) was evaluated by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants with low IGFBP-2 levels were characterized by a higher body fat mass (P < 0.0001), insulin resistance (P < 0.0001), higher plasma triglyceride (TG) (P < 0.0001), and lower HDL-cholesterol levels (P < 0.0001) in a sex-independent manner. IGFBP-2 levels were inversely correlated with hepatic fat fraction in both men (r = -0.36, P < 0.0001) and women (r = -0.40, P < 0.0001). IGFBP-2 concentrations were negatively associated with hepatic fat fraction independently of age and VAT in both men (R2 = 0.23, P = 0.012) and women (R2 = 0.27, P = 0.028). In conclusion, our findings show that even in asymptomatic, apparently healthy individuals, low IGFBP-2 levels are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content in a VAT-independent manner. However, IGFBP-2 does not appear to influence the established sexual dimorphism observed for metabolic variables and hepatic fat fraction. Additional studies are required to better understand the relationships between IGFBP-2 and liver fat content.NEW & NOTEWORTHY Faced with a paucity of reliable clinical etiologic markers for fatty liver, this research article demonstrates, for the first time, that low blood levels of the protein IGFBP-2 are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content independently of visceral fat volume and sex, even in asymptomatic, apparently healthy individuals.

Chest Pain Evaluation: Diagnostic Testing.

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice.

La douleur ou la gêne thoracique sont des symptômes fréquents qui peuvent poser un dilemme diagnostique pour de nombreux médecins. Les erreurs de diagnostic d'une cause aiguë ou chronique progressive d'origine cardiaque peuvent d'ailleurs entraîner un risque considérable de morbidité et de mortalité. La présente synthèse porte sur les différentes options et modalités d'établissement du diagnostic et de la gravité d'une coronaropathie. Un algorithme efficace pour le choix des tests doit être adapté à chaque patient afin de maximiser l'exactitude diagnostique dans les plus brefs délais, de déterminer le pronostic à court et à long terme, et de permettre une mise en œuvre de traitements fondés sur des données probantes tout en tenant compte des coûts. Un algorithme décisionnel a donc été conjointement mis au point (www.chowmd.ca/cadtesting) et pourrait être largement adopté dans la pratique clinique.

Overweight, Obesity, and CVD Risk: a Focus on Visceral/Ectopic Fat.

PURPOSE OF REVIEW: Despite its prevalence and well-documented impact on population health, obesity has not emerged as a strong independent risk factor for cardiovascular disease after control for intermediate risk factors. The purpose of this brief narrative review is to highlight results from imaging studies that have not only documented the remarkable heterogeneity of body fat topography but also the importance of visceral adiposity as a key body fat depot associated with cardiovascular disease risk and type 2 diabetes. RECENT FINDINGS: Simple tools are also discussed in order to refine cardiometabolic risk assessment in persons with overweight/obesity. It is proposed that four lifestyle vital signs should be considered in clinical practice to improve discrimination of health risk in individuals with overweight/obesity: waist circumference as a simple marker of abdominal adiposity, cardiorespiratory fitness, overall diet quality, and level of reported physical activity. Heterogeneity of obesity is proposed as an example of a condition that would benefit from a precision lifestyle medicine approach.

Evaluation of Adiposity and Cognitive Function in Adults.

Importance: Excess adipose tissue increases other cardiovascular risk factors, which may be associated with vascular brain injury and cognitive impairment. However, the extent to which the amount and distribution of adipose tissue may be associated with lower cognitive scores, independent of its association with cardiovascular risk factors, is not well characterized. Objective: To investigate the association of adiposity on vascular brain injury and cognitive scores. Design, Setting, and Participants: A total of 9189 participants from the Canadian Alliance for Healthy Hearts and Minds (CAHHM) and the Prospective Urban Rural Epidemiological-Mind (PURE-MIND) cohort studies were included in this cross-sectional analysis. Of these adults, 9166 underwent bioelectrical impedance analysis to assess body fat (BF) percentage, and 6773 underwent magnetic resonance imaging to assess vascular brain injury and measure visceral adipose tissue (VAT) volume. Participants from CAHHM were recruited from January 1, 2014, to December 31, 2018, and PURE-MIND participants were recruited from January 1, 2010, to December 31, 2018. Both CAHHM and PURE-MIND comprise multisite, population-based cohorts. Participants from CAHHM are from Canada, and PURE-MIND participants are from Canada or Poland. Data analysis was performed from May 3 to November 24, 2021. Exposures: The percentage of BF and VAT were modeled as sex-specific quartiles. Vascular brain injury was defined as high white matter hyperintensities or silent brain infarction. Multivariable mixed models were used to examine factors associated with reduced cognitive scores. Main Outcomes and Measures: Cognitive function was assessed using the Digital Symbol Substitution Test (DSST; scores range from 0 to 133, with lower scores indicating lower cognitive function) and Montreal Cognitive Assessment (scores range from 0 to 30, with a score of ≥26 denoting normal cognitive function). Reduced cognition was defined as a DSST score less than 1 SD below the mean. Cardiovascular risk was assessed using the INTERHEART Risk Score (IHRS; scores range from 0 to 48; low risk is defined as a score of 0 to 9, moderate risk as 10 to 16, and high risk as 17 or higher). Results: A total of 9189 adults (mean [SD] age, 57.8 [8.8] years; 5179 [56.4%] women; and 1013 [11.0%] East and Southeast Asian; 295 [3.2%] South Asian; 7702 [83.8%] White European; and 179 [1.9%] other, including Black, Indigenous, mixed, and unknown ethnicity) participated in the study. Visceral adipose tissue was highly correlated with body adiposity measured by BF percentage (r = 0.76 in women; r = 0.70 in men). Cardiovascular risk factors increased with increasing BF percentage with the fourth quartile IHRS at 13.8 (95% CI, 13.5-14.0; P < .001 for trend) and with VAT with the fourth quartile IHRS at 13.3 (95% CI, 13.0-13.5; P < .001 for trend). Vascular brain injury increased with increasing BF percentage with the fourth quartile value at 8.6% (95% CI, 7.5%-9.8%; P = .007 for trend) and with increasing VAT with fourth quartile value at 7.2% (95% CI, 6.0-8.4; P = .05 for trend). Cognitive scores were lower with increasing BF percentage with the fourth quartile score of 70.9 (95% CI, 70.4-71.5; P < .001 for trend) and for VAT with the fourth quartile score of 72.8 (95% CI, 72.1-73.4; P < .001 for trend). For every 1-SD increase in BF percentage (9.2%) or VAT (36 mL), the DSST score was lower by 0.8 points (95% CI, 0.4-1.1; P < .001) for BF percentage and lower by 0.8 points (95% CI, 0.4-1.2; P < .001) for VAT, adjusted for cardiovascular risk factors and vascular brain injury. The population attributable risk for reduced DSST score for higher BF percentage was 20.5% (95% CI, 7.0%-33.2%) and for VAT was 19.6% (95% CI, 2.0%-36.0%). Higher BF percentage and VAT were not associated with Montreal Cognitive Assessment scores. Conclusions and Relevance: In this cross-sectional study, generalized and visceral adiposity were associated with reduced cognitive scores, after adjustment for cardiovascular risk factors, educational level, and vascular brain injury. These results suggest that strategies to prevent or reduce adiposity may preserve cognitive function.

Ambiguous and Incomplete: Natural Language Processing Reveals Problematic Reporting Styles in Thyroid Ultrasound Reports.

OBJECTIVE: Natural language processing (NLP) systems convert unstructured text into analyzable data. Here, we describe the performance measures of NLP to capture granular details on nodules from thyroid ultrasound (US) reports and reveal critical issues with reporting language. METHODS: We iteratively developed NLP tools using clinical Text Analysis and Knowledge Extraction System (cTAKES) and thyroid US reports from 2007 to 2013. We incorporated nine nodule features for NLP extraction. Next, we evaluated the precision, recall, and accuracy of our NLP tools using a separate set of US reports from an academic medical center (A) and a regional health care system (B) during the same period. Two physicians manually annotated each test-set report. A third physician then adjudicated discrepancies. The adjudicated "gold standard" was then used to evaluate NLP performance on the test-set. RESULTS: A total of 243 thyroid US reports contained 6,405 data elements. Inter-annotator agreement for all elements was 91.3%. Compared with the gold standard, overall recall of the NLP tool was 90%. NLP recall for thyroid lobe or isthmus characteristics was: laterality 96% and size 95%. NLP accuracy for nodule characteristics was: laterality 92%, size 92%, calcifications 76%, vascularity 65%, echogenicity 62%, contents 76%, and borders 40%. NLP recall for presence or absence of lymphadenopathy was 61%. Reporting style accounted for 18% errors. For example, the word "heterogeneous" interchangeably referred to nodule contents or echogenicity. While nodule dimensions and laterality were often described, US reports only described contents, echogenicity, vascularity, calcifications, borders, and lymphadenopathy, 46, 41, 17, 15, 9, and 41% of the time, respectively. Most nodule characteristics were equally likely to be described at hospital A compared with hospital B. CONCLUSIONS: NLP can automate extraction of critical information from thyroid US reports. However, ambiguous and incomplete reporting language hinders performance of NLP systems regardless of institutional setting. Standardized or synoptic thyroid US reports could improve NLP performance.

Normal sex and age-specific parameters in a multi-ethnic population: a cardiovascular magnetic resonance study of the Canadian Alliance for Healthy Hearts and Minds cohort.

BACKGROUND: Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. METHODS AND RESULTS: Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p < 0.001). Ventricular ejection fraction was significantly diminished in males as compared to females (p < 0.001). Indexed left ventricular (LV) end-systolic, end-diastolic volumes, mass and right ventricular (RV) parameters significantly decreased as age increased for both sexes (p < 0.001). For females, but not men, mean LV and RVEF significantly increased with age (p < 0.001). CONCLUSION: Using anatomically correct contouring methodology, we provide accurate sex and age-specific normal reference values for CMR parameters derived from the largest, multi-ethnic population free of CVD to date. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02220582. Registered 20 August 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02220582 .

Accuracy of stroke volume measurement with phase-contrast cardiovascular magnetic resonance in patients with aortic stenosis.

BACKGROUND: Phase contrast (PC) cardiovascular magnetic resonance (CMR) in the ascending aorta (AAo) is widely used to calculate left ventricular (LV) stroke volume (SV). The accuracy of PC CMR may be altered by turbulent flow. Measurement of SV at another site is suggested in the presence of aortic stenosis, but very few data validates the accuracy or inaccuracy of PC in that setting. Our objective is to compare flow measurements obtained in the AAo and LV outflow tract (LVOT) in patients with aortic stenosis. METHODS: Retrospective analysis of patients with aortic stenosis who had CMR and echocardiography. Patients with mitral regurgitation were excluded. PC in the AAo and LVOT were acquired to derive SV. LV SV from end-systolic and end-diastolic tracings was used as the reference measure. A difference ≥ 10% between the volumetric method and PC derived SVs was considered discordant. Metrics of turbulence and jet eccentricity were assessed to explore the predictors of discordant measurements. RESULTS: We included 88 patients, 41% with bicuspid aortic valve. LVOT SV was concordant with the volumetric method in 79 (90%) patients vs 52 (59%) patients for AAo SV (p = 0.015). In multivariate analysis, aortic stenosis flow jet angle was a strong predictor of discordant measurement in the AAo (p = 0.003). Mathematical correction for the jet angle improved the concordance from 59 to 91%. Concordance was comparable in patients with bicuspid and trileaflet valves (57% and 62% concordance respectively; p = 0.11). Accuracy of SV measured in the LVOT was not influenced by jet eccentricity. For aortic regurgitation quantification, PC in the AAo had better correlation to volumetric assessments than LVOT PC. CONCLUSION: LVOT PC SV in patients with aortic stenosis and eccentric jet might be more accurate compared to the AAo SV. Mathematical correction for the jet angle in the AAo might be another alternative to improve accuracy.

The impact of reporting magnetic resonance imaging incidental findings in the Canadian alliance for healthy hearts and minds cohort.

BACKGROUND: In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. METHODS: Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. RESULTS: Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7-8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. CONCLUSION: The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .

Incidental detection of myocardial clefts in a patient with acute inferior ST-segment elevation myocardial infarction: a very unusual and potentially ominous association-a case-report.

BACKGROUND: The crescent availability of high-resolution cardiac imaging allows detection of myocardial structural variations. Differentiate these entities from others with different clinical significance can be challenging. Clinicians should be familiar with myocardial clefts to avoid erroneous diagnosis. CASE SUMMARY: A 63-year-old smoker man alerted the emergency medical system for sudden chest pain. The electrocardiogram showed Pardee wave in inferior leads. Coronary angiography evidenced a 100% occlusion of right coronary artery that was treated by angioplasty and drug-eluting stent implantation with optimal angiographic result. At ventriculography, two fissure-like protrusion were observed in the inferior wall. Urgent transthoracic echocardiogram (TTE) demonstrated two deep fissures on the mid-inferior wall, contained by a thin sub-epicardial layer, with sub-total obliteration during systole. A diagnosis of myocardial clefts was suspected and after Heart Team discussion, a conservative strategy was proposed. Early cardiac magnetic resonance (CMR) confirmed two myocardial crypts on the mid-inferior wall. Stability of myocardial fissures and absence of left ventricular remodelling was confirmed by TTE, in a 2 years of follow-up period. DISCUSSION: Myocardial cleft should always be considered in the differential diagnosis of myocardial wall defects. In a patient presenting with an acute myocardial infarction, the main differential diagnosis is pseudoaneurysm. In this setting modified TTE views and meticulous analysis of CMR sequences are recommended to confirm the diagnosis and estimate the risk of myocardial rupture.

Left ventricular asymmetric remodeling and subclinical left ventricular dysfunction in patients with calcific aortic valve stenosis - Results from a subanalysis of the PROGRESSA study.

BACKGROUND: LV asymmetric remodeling (LVAR) is a feature commonly found in AS patients and it is presumed to be mainly related to the severity of valve stenosis. The aim of this study was to determine the associated factors and impact on left ventricular (LV) systolic function of LVAR in patients with mild and moderate aortic valve stenosis (AS). METHODS: Clinical, Doppler-echocardiographic and computed-tomographic data of 155 AS patients with preserved LV ejection fraction (≥50%) prospectively recruited in the PROGRESSA study (NCT01679431) were analyzed. LVAR was defined as a septal wall thickness ≥ 13 mm and a ratio of septal/posterior wall thickness > 1.5. LV global longitudinal strain (LV-GLS) was available in 129 patients. Plasma levels of N-terminal natriuretic B-type peptides (Nt-proBNP) were also measured. RESULTS: Mean age was 63 ± 15 years (70% men). LVAR was present in 21% (n = 33) of patients. A series of nested multivariate analysis revealed that age was the only factor associated with LVAR (all p ≤ 0.03). Additionally, these patients had higher baseline Nt-proBNP ratio (median [25-75 percentiles]: 1.04 [0.66-2.41] vs. 0.65 [0.33-1.19], p = 0.02), and significantly reduced LV-GLS (17.9[16.6-19.5] vs. 19.3[17.4-20.7] |%|, p = 0.04). A 1:1 matched analysis showed a significant association of LVAR with reduced LV-GLS (17.9[16.6-19.5] vs. 19.8[18.1-20.7] |%|, p = 0.02) and elevated Nt-proBNP (134[86-348] vs. 83[50-179]pg/ml, p = 0.03). Multivariable analysis also revealed that LVAR remains significantly associated with reduced LV-GLS (p = 0.03) and elevated Nt-proBNP (p = 0.001). LVAR was significantly associated with increased risk of major adverse cardiac events and death (Hazard ratio [95% confidence interval]: 2.32[1.28-4.22], p = 0.006). CONCLUSIONS: LVAR was found in ~20% of patients with mild or moderate AS and was not related to the degree of AS severity or concomitant comorbidities, but rather to older age. LVAR was significantly associated with reduced LV longitudinal systolic function, increased Nt-proBNP levels, and higher risk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature.

Correlates of Coronary Artery Calcification Prevalence and Severity in Patients With Heterozygous Familial Hypercholesterolemia.

BACKGROUND: Determinants of coronary artery calcification (CAC) prevalence and severity in heterozygous familial hypercholesterolemia (HeFH) remain understudied. The objective of this cross-sectional study was to investigate correlates of CAC in patients with HeFH. METHODS: A CAC score was calculated by a noncontrast computed tomography scan in women (n = 68) and men (n = 78) with genetically defined HeFH. We classified CAC prevalence and severity using 3 categories: CAC score = 0 Agatston Unit (AU), CAC score = 1-100 AU, and CAC score > 100 AU. Information on potential correlates of CAC including familial and personal health history, cardiovascular risk factors, lipid-lowering medication, and lifestyle habits was collected. RESULTS: A total of 95 patients had prevalent CAC. Independent correlates of CAC prevalence and severity included age (odds ratio [OR] per 10 years: 5.06, 95% confidence interval [CI]: 3.19, 7.93, P < 0.0001), family history of premature cardiovascular disease (OR: 3.88, 95% CI: 1.71, 8.81, P = 0.001), male sex (OR: 3.40, 95% CI: 1.49, 7.78, P = 0.004), statin use (OR: 15.5, 95% CI: 1.89, 126, P = 0.01), diet quality assessed with the Alternative Healthy Eating Index score (OR per 1 standard deviation: 0.59, 95% CI: 0.39, 0.90, P = 0.01), ever smoking (OR: 3.06, 95% CI: 1.20, 7.81, P = 0.02), receptor-negative genotype (OR: 3.17, 95% CI: 1.16, 8.66, P = 0.02), lipoprotein(a) year-score (OR per 1 standard deviation of log-transformed year-score: 1.53, 95% CI: 0.99, 2.36, P = 0.05). CONCLUSIONS: In individuals with HeFH, age, family history of premature cardiovascular disease, sex, statin use, diet quality, smoking status, the LDLR genotype, and lipoprotein(a) concentrations were independently associated with CAC prevalence and severity.

CONTEXTE: Les déterminants de la prévalence et de la sévérité de la calcification des artères coronaires (CAC) dans l'hypercholestérolémie familiale hétérozygote (HFHe) demeurent peu étudiés. L'objectif de cette étude transversale était d'identifier les corrélats de la CAC chez des patients atteints d'HFHe. MÉTHODOLOGIE: Un score calcique coronarien (SCC) a été calculé par un examen de tomodensitométrie sans contraste chez des femmes (n = 68) et des hommes (n = 78) avec HFHe génétiquement définie. Nous avons classé la prévalence et la gravité de la CAC en trois catégories : SCC = 0 unité d'Agatston (UA), SCC = 1 à 100 UA et SCC > 100 UA. Des renseignements ont été recueillis sur des corrélats potentiels de la CAC, dont les antécédents médicaux familiaux et personnels, les facteurs de risque cardiovasculaire, les médicaments hypolipidémiants et les habitudes de vie. RÉSULTATS: Au total, 95 patients présentaient une CAC. Les corrélats indépendants de la prévalence et de la gravité de la CAC comprenaient l'âge (rapport de cotes [RC] par tranche de 10 ans : 5,06; intervalle de confiance [IC] à 95 % : 3,19 à 7,93; p < 0,0001), des antécédents familiaux de maladie cardiovasculaire précoce (RC : 3,88; IC à 95 % : 1,71 à 8,81; p = 0,001), le sexe masculin (RC : 3,40; IC à 95 % : 1,49 à 7,78; p = 0,004), l'emploi de statines (RC : 15,5; IC à 95 % : 1,89 à 126; p = 0,01), la qualité du régime alimentaire évaluée selon le score AHEI (Alternative Healthy Eating Index) (RC par écart-type : 0,59; IC à 95 % : 0,39 à 0,90; p = 0,01), le tabagisme (RC : 3,06; IC à 95 % : 1,20 à 7,81; p = 0,02), le génotype récepteur-négatif (RC : 3,17; IC à 95 % : 1,16 à 8,66; p = 0,02) et le score lipoprotéine(a)-année (RC par écart-type du score-année transformé en logarithme : 1,53; IC à 95 % : 0,99 à 2,36; p = 0,05). CONCLUSIONS: Chez les personnes atteintes d'HFHe, l'âge, les antécédents familiaux de maladie cardiovasculaire précoce, le sexe, l'emploi de statines, la qualité du régime alimentaire, le statut de tabagisme, le génotype du LDLR et les concentrations de lipoprotéine(a) ont été associés de façon indépendante à la prévalence et à la gravité de la CAC.

Effect of Regional Upper Septal Hypertrophy on Echocardiographic Assessment of Left Ventricular Mass and Remodeling in Aortic Stenosis.

BACKGROUND: Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). METHODS: One hundred six patients (mean age, 63 ± 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ≥ 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. RESULTS: The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 ± 31 g; BSB, +59 ± 32 g; ML, +54 ± 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10 ± 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB). CONCLUSIONS: Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.

Novel Z Scores to Correct Biases Due to Ventricular Volume Indexing to Body Surface Area in Adolescents and Young Adults.

BACKGROUND: Reference values for cardiac magnetic resonance imaging (cMRI) in children and young adults are scarce. This leads to risk stratification of patients with congenital heart diseases being based on volumes indexed to body surface area (BSA). We aimed to produce cMRI Z score equations for ventricular volumes in children and young adults and to test whether indexing to BSA resulted in an incorrect assessment of ventricular dilation according to sex, body composition, and growth. METHODS: We retrospectively included 372 subjects aged < 26 years with either normal hearts or conditions with no impact on ventricular volumes (reference group), and 205 subjects with repaired tetralogy of Fallot (TOF) aged < 26 years. We generated Z score equations by means of multivariable regression modelling. Right ventricular dilation was assessed with the use of Z scores and compared with indexing to BSA in TOF subjects. RESULTS: Ventricular volume Z scores were independent from age, sex, and anthropometric measurements, although volumes indexed to BSA showed significant residual association with sex and body size. In TOF subjects, indexing overestimated dilation in growing children and underestimated dilation in female compared with male subjects, and in overweight compared with lean subjects. CONCLUSIONS: Indexed ventricular volumes measured with cMRI did not completely adjust for body size and resulted in a differential error in the assessment of ventricular dilation according to sex and body size. Our proposed Z score equations solved this problem. Future studies should evaluate if ventricular volumes expressed as Z scores have a better prognostic value than volumes indexed to BSA.

Computed tomography coronary angiography for patients with heart failure (CTA-HF): a randomized controlled trial (IMAGE-HF 1C).

AIMS: This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. Invasive coronary angiography (ICA) is used to investigate HF patients. CCTA may be a non-invasive cost-effective alternative to ICA. This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. METHODS AND RESULTS: This multicentre, international trial enrolled patients with HF of unknown aetiology. The primary outcome was the cost of CCTA vs. ICA strategies at 12 months. Clinical outcomes were also collected. An 'intention-to-diagnose' analysis was performed and a secondary 'as-tested' analysis was based on the modality received. Two hundred and forty-six patients were randomized (age = 57.8 ± 11.0 years, ejection fraction = 30.1 ± 10.1%). The severity of coronary artery disease was similar in both groups. In the 121 CCTA patients, 93 avoided ICA. Rates of downstream ischaemia and viability testing were similar for both arms. There were no significant differences in the composite clinical outcomes or quality of life measures. The cost of CCTA trended lower than ICA [CDN -$871 (confidence interval, CI -$4116 to $3028)]. Using an 'as-tested' analysis, CCTA was associated with a decrease in healthcare costs (CDN -$2932, 95% CI -$6248 to $746). CONCLUSION: In patients with HF of unknown aetiology, costs were not statistically different between the CCTA and ICA strategies. CLINICAL TRIALS.GOV: NCT01283659.

Ventricular Arrhythmia in Septal and Apical Hypertrophic Cardiomyopathy: The French-Canadian Experience.

Background: Apical hypertrophic cardiomyopathy (aHCM) is thought to have a more benign clinical course compared to septal HCM (sHCM), but most data have been derived from Asian cohorts. Comparative data on clinical outcome in Caucasian aHCM cohorts are scarce, and the results are conflicting. The aim of this study was to estimate the prevalence and outcome of aHCM in French-Canadians of Caucasian descent. Methods and results: We conducted a retrospective, single-center cohort study. The primary endpoint was a composite of documented sustained ventricular arrhythmia (VA), appropriate ICD therapy, arrhythmogenic syncope, cardiac arrest, or all-cause mortality. A total of 301 HCM patients (65% males) were enrolled including 80/301 (27%) with aHCM and 221/301 (73%) with sHCM. Maximal wall thickness was similar in both groups. Left ventricular apical aneurysm was significantly more common in aHCM (10 vs. 0.5%; p < 0.001). The proportion of patients with myocardial fibrosis ≥ 15% of the left ventricular mass was similar between aHCM and sHCM (21 vs. 24%; p = 0.68). Secondary prevention ICDs were more often implanted in aHCM patients (16 vs. 7%; p = 0.02). The primary endpoint occurred in 26% of aHCM and 10.4% of sHCM patients (p = 0.001) and was driven by an increased incidence of sustained VA (10 vs. 2.3%; p = 0.01). Multivariate analysis identified apical aneurysm and a phenotype of aHCM as independent predictors of the primary endpoint and the occurrence of sustained ventricular tachycardia. Unexplained syncope and a family history of sudden cardiac death were additional predictors for sustained VA. Apical HCM was associated with an increased risk of ventricular arrhythmia even when excluding patients with apical aneurysm. Conclusions: The phenotype of apical HCM is much more common in French-Canadians (27%) of Caucasian descent compared to other Caucasian HCM populations. Apical HCM in French-Canadians is associated with an increased risk for ventricular arrhythmia.

Hemodynamic performance of the balloon-expandable SAPIEN 3 valve as assessed by cardiac magnetic resonance.

BACKGROUND: Scarce data exist on transcatheter heart valve (THV) performance evaluated by cardiac magnetic resonance (CMR) in newer generation THV patients. Furthermore, it has been suggested that echocardiographic evaluation after TAVR may inaccurately assess residual AR in some patients. This study aimed to determine the incidence and severity of aortic regurgitation (AR) assessed by CMR in patients undergoing TAVR with the SAPIEN 3 valve, and evaluate the agreement between CMR and transthoracic echocardiography (TTE) on the assessment of AR severity in such patients. METHODS: This multicentric observational study included 146 SAPIEN 3 patients with TTE and CMR within the month following their procedure. According to the CMR regurgitation fraction (RF), AR was considered mild and moderate-severe if the RF was 15-<30% and ≥ 30%, respectively. TTE exams followed VARC-2 recommendations. RESULTS: By CMR, SAPIEN 3 recipients displayed a mean RF of 5.0 ± 6.1%, and mild and moderate-severe AR rates of 3.4% and 0.7%, respectively. The agreement between CMR-TTE was modest (weighted κ = 0.2640, p<0.001), due to an overestimation of AR severity by TTE. A historical cohort of 139 SAPIEN XT patients with a post-procedure CMR, displayed a mean RF of 9.6 ± 10.7% and mild and moderate-severe AR rates of 18.7% and 3.6%, respectively (p < .001 vs. SAPIEN 3 group). CONCLUSIONS: SAPIEN 3 recipients exhibited very low rates of residual AR by CMR, suggesting a surgical-like performance regarding AR with this newer generation THV. TTE tended to overestimate the severity of AR, particularly among mild AR patients.