Importance Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy.

Importance:Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective:To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants:A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures:Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures:The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results:Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance:These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration:ClinicalTrials.gov Identifier: NCT01915615.

Physiology assessment of coronary lesion prepercutaneous coronary intervention (PCI) using hyperemic and nonhyperemic pressure ratios is useful to determine if a lesion requires treatment. Whether the physiology after PCI is superior to angiography guidance only is unknown. The study sought to investigate whether post-PCI physiology improves clinical outcomes compared with standard angiographic guidance. All-comers patients referred for diagnostic angiography and possible PCI were recruited in a high-volume tertiary care hospital. After uncomplicated PCI, patients were randomized to angiography guidance or target vessel physiology, including nonhyperemic pressure ratio (resting distal coronary pressure to aortic pressure ratio and diastolic pressure ratio) and fractional flow reserve. The primary outcome was the rate of target vessel failure, including cardiac death, myocardial infarction, and target vessel revascularization at 18 months post-PCI. Angina score, medications, and quality of life were also assessed. Two hundred twenty-one patients were randomized in the angiography group (110 patients, 166 lesions) and the physiology group (111 patients, 159 lesions). Immediate post-PCI physiology results were deemed suboptimal in 22 (17%) cases, and operators performed further optimization steps. Final post-PCI results were resting distal coronary pressure to aortic pressure ratio of 0.95±0.04, the diastolic pressure ratio of 0.94±0.06, and the fractional flow reserve of 0.90±0.07. Ultimately, 9 lesions (7%) remained with fractional flow reserve values ≤0.80. At 18-month follow-up, target vessel failure was 17.4% in the angiography group and 18% in the physiology group (P=0.88). Rates of cardiac death (1% versus 0%; P=0.32), myocardial infarction (13% versus 11%; P=0.66), and target vessel revascularization (4% versus 7%; P=0.24) remained similar in both groups. No difference in angina score, medication, or quality of life was found. In all-comers patients undergoing uncomplicated PCI, routine post-PCI physiology assessment was not associated with clinical benefit compared with standard angiographic guidance. Further study is required to determine how post-PCI physiology guidance can be helpful in selected lesions. URL: https://clinicaltrials.gov/; Unique identifier: NCT04929496.

Visceral adipose tissue (VAT) and hepatic fat (HF) contribute to multiple health risks, including diabetes, hypertension, cardiovascular disease, cognitive decline, and cancer. The objective of this study is to determine whether VAT and HF are associated with carotid atherosclerosis beyond traditional cardiovascular risk factors. Participants in the Canadian Alliance of Healthy Hearts and Minds (CAHHM) cohort study (n = 6760; average age= 57.1; 54.9

Background The role of advanced (cardiac magnetic resonance [CMR] or positron emission tomography [PET]) vs single-photon emission computerized tomography (SPECT) ischemia imaging to guide management remains unclear in patients with ischemic heart failure (IHF). The primary aim was to determine the effect of imaging modality on a composite cardiovascular endpoint and cardiac death in patients with IHF who require ischemia assessment. Methods Patients with IHF were randomized to advanced or SPECT imaging. A parallel registry also was performed. The primary endpoint was the composite of cardiac death, infarction, arrest, and cardiac rehospitalization. The key secondary endpoint was cardiac death. Results Patients in the randomized population (advanced imaging [PET or CMR; n = 64] or SPECT [n = 56]) had a cumulative incidence rate (CIR) for the primary endpoint of 33.1% and 33.0%, respectively (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.49, 1.80, P = 0.853). CIRs for cardiac death were 13.8% and 25.1%, respectively (HR 0.62, 95% CI 0.25, 1.80, P = 0.296).In the parallel registry (n = 336 advanced; n = 216 SPECT), the primary endpoint CIRs were 31.2% and 35.3%, respectively (HR 0.81, 95% CI 0.56, 1.19, P = 0.284). CIRs for cardiac death were 11.0% and 16.6%, respectively (HR 0.53, 95% CI 0.27, 1.04, P = 0.066). Patients were followed for a median (interquartile range) of 24.1 (11.6, 27.5) months.Pooled analysis from the randomized and registry populations revealed a significant benefit of advanced imaging for reduction of cardiac death (HR 0.56, 95% CI 0.33, 0.96, P = 0.04) with minimal heterogeneity (I2 = 0%). Conclusion Among IHF patients assessed for ischemia, advanced imaging (PET or CMR) was not associated with reduced composite cardiac events, compared to SPECT. Clinical Trial Registration NCT01288560.

BACKGROUND:In the EASY-PREDICT Study, patients were randomized to angiography-guidance or post-percutaneous coronary intervention (PCI) physiology-guidance. Discordance between resting and hyperemic physiology post-PCI might have a different relationship with clinical outcomes. AIMS:The EASY-PREDICT study showed that routine post-PCI physiology assessment was not associated with improved outcomes compared to angiography-guidance only. We aimed to assess whether resting and hyperemic post-PCI physiology had a different clinical impact. METHODS:All-comer patients referred for diagnostic angiography and possible PCI were recruited in a high-volume university hospital and randomized after uncomplicated PCI to angiography-only or target vessel physiology. We studied the concordance and discordance between resting (dPR) and hyperemic (FFR) physiologic parameters post-PCI using ischemic thresholds (dPR ≤ 0.89 and FFR ≤ 0.80) and clinical outcomes up to 18 months post-PCI. RESULTS:A total of 221 patients (325 lesions) with successful PCI were randomized to either group, 219 of which were included in the per protocol analysis. In the physiology group, 132 lesions with available post-PCI physiology were included and 109 (82.6%) had final concordant physiology results post-PCI. Discordance was observed in 15.15% of lesions, 2.3% FFR ischemic (dPR-|FFR+) and 12.9% dPR ischemic (dPR+|FFR-) respectively. At 18 months clinical follow-up, Target Vessel Failure (TVF) was 12.3% in the concordant sub-group whereas TVF was 40.0% in the discordant subgroup. CONCLUSIONS:After PCI, physiology discordance between dPR and FFR occurred in ~15% of the cases. Patients with discordant physiology results post-PCI appeared to have higher TVF rates compared to concordant physiology sub-groups.

Excess liver fat (LF) is associated with low cardiorespiratory fitness (CRF), low physical activity, and a deteriorated cardiometabolic health profile including increased visceral adipose tissue (VAT). Whether the association between LF and CRF is mediated by visceral adiposity is unknown. We studied the contribution of VAT to the relationship between CRF and LF in asymptomatic women and men. The sample included 320 participants (43% women) who underwent LF quantification by magnetic resonance spectroscopy. VAT was measured by magnetic resonance imaging, CRF using maximal cardiorespiratory exercise testing, and moderate-to-vigorous intensity physical activity (MVPA) using a 3-day journal. Mean age was 50.3 ± 8.6 years, waist circumference was 89.3 ± 11.4 cm, and LF content was 4.3 ± 5.7%. LF was inversely correlated with CRF (p < 0.0001), MVPA (p < 0.05) and cardiometabolic health score (p < 0.0001), and positively related with VAT (p < 0.0001) in both sexes. Significantly higher levels of VAT (p < 0.0001) and subcutaneous adipose tissue (p < 0.0001) and a worsening cardiometabolic health score (p < 0.05) and CRF (p = 0.0001) were found across increasing sex-specific tertiles of LF levels. Lower levels of LF (p < 0.01) and VAT (p < 0.0001) and a higher cardiometabolic health score (p < 0.0001) and MVPA (p < 0.05) were noted across increasing sex-specific CRF tertiles. Multivariable regression analyses showed that visceral adiposity explained the majority of the variance in LF in both sexes (p < 0.0001). Finally, serial mediation analyses revealed that VAT but not body fat percentage was a mediator in the relationship between CRF and LF in both sexes. Thus, visceral adiposity appears to be an important mediator in the relationship between CRF and LF, even after controlling for total adiposity.

Background: Maple syrup, a minimally transformed sweetener rich in polyphenols, can exert a action and improve metabolic parameters in animal models. However, no randomized clinical trial has investigated this. Objectives: This study aims to determine whether replacing refined sugars with an equivalent quantity of maple syrup could decrease key cardiometabolic risk factors in individuals with mild metabolic alterations. Methods: In a randomized, double-blind, controlled crossover trial with 42 overweight adults with mild cardiometabolic alterations, participants were instructed to substitute 5% of their total caloric intake from added sugars with either maple syrup or an artificially flavored sucrose syrup for 8 wk. The primary outcome included changes in glucose homeostasis, whereas secondary outcomes were changes in other cardiometabolic risk factors such as blood pressure, anthropometric indices, and blood lipid profiles. Exploratory outcomes involved analyzing changes in gut microbiota composition. Results: Replacing refined sugars with maple syrup over 8 wk decreased the glucose area under the curve when compared with substituting refined sugars with sucrose syrup, as determined during the oral glucose tolerance test, leading to a significant difference between the intervention arms (-50.59 +/- 201.92 compared with 29.93 +/- 154.90; P < 0.047). Substituting refined sugar with maple syrup also significantly decreased android fat mass (-7.83 +/- 175.05 g compared with 67.61 +/- 206.71 g; P = 0.02) and systolic blood pressure (-2.72 +/- 8.73 mm Hg compared with 0.87 +/- 8.99 mm Hg; P = 0.03). No changes in the blood lipid profile were observed. As an exploratory outcome, we further observed that substituting refined sugars with maple syrup promoted selective taxonomic changes in the gut microbiota such as a significant reduction in the abundance of Klebsiella species and decreased microbial functions associated with bacterial-induced cytokine response, when compared with substitution with sucrose syrup. Conclusions: Substituting refined sugars with maple syrup in individuals with mild metabolic alterations result in a significantly greater reduction of key cardiometabolic risk factors compared with substitution with sucrose syrup, in association with specific changes in gut microbiota. The role of the gut microbiota in these effects remains to be further explored.

This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared with 86 healthy males in the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, P < 0.0001) and lower subcutaneous (-56.2 mL, P < 0.05) and liver (-3.3%, P < 0.05) fat compared with the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (-0.8 ± 0.9 kg, P < 0.05) and body mass index (-0.3 ± 0.3 kg/m2, P < 0.05). Loss of fat mass (-1.5 ± 1.0 kg, P < 0.001) and a trend toward an increased lean mass (+0.8 ± 1.2 kg, P < 0.07) were observed. Visceral adiposity (-14.1 ± 14.2 mL, P < 0.01) and waist circumference (-3.2 ± 1.7 cm, P < 0.0001) decreased, whereas subcutaneous (-2.7 ± 5.1 mL, NS), liver (-0.5 ± 0.9%, NS), and cardiac (-0.3 ± 2.3 mL, NS) fat remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss.NEW & NOTEWORTHY Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males.

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.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population with no effective drug treatments available. Previous animal studies reported that a polyphenol-rich extract from the Amazonian berry camu-camu (CC) prevented hepatic steatosis in a mouse model of diet-induced obesity. This study aims to determine the impact of CC on hepatic steatosis (primary outcome) and evaluate changes in metabolic and gut microbiota profiles (exploratory outcomes). A randomized, double-blind, placebo- controlled crossover trial is conducted on 30 adults with overweight and hypertriglyceridemia, who consume 1.5 g of CC capsules or placebo daily for 12 weeks. CC treatment decreases liver fat by 7.43%, while it increases by 8.42% during the placebo intervention, showing a significant difference of 15.85%. CC decreases plasma aspartate and alanine aminotransferases levels and promotes changes in gut microbiota composition. These findings support that polyphenol-rich prebiotic may reduce liver fat in adults with overweight, reducing the risk of developing NAFLD.

Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 +/- 8.6 years) and 131 women (51.8 +/- 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat >5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations (p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD.

BACKGROUND AND AIMS:Epicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored. Our purpose was to investigate the contribution of VAT in the relationships between CRF, physical activity (PA) and epicardial adipose tissue (EAT) in asymptomatic women and men. METHODS AND RESULTS:We examined the associations between EAT and VAT measured by magnetic resonance imaging, CRF measured by cardiopulmonary exercise testing, and PA assessed using pedometers and a 3-day PA journal in 239 apparently healthy adults (43 % women). Participants were compared according to EAT tertiles and CRF level in both sexes. Participants with the highest EAT level presented more VAT (p < 0.001), lower CRF (p < 0.01), and a more deteriorated cardiometabolic health score (p < 0.01) than those with the lowest EAT level. CRF was negatively associated with EAT in both sexes (p < 0.01). No significant relationship was found with PA (p = NS). Stepwise multivariable regression analyses showed that VAT explained most of the variance in EAT in women and men. Mediation analyses confirmed that VAT was a mediator of the association between CRF and EAT in both sexes. CONCLUSION:In women and men, VAT appears as a major mediator of the association between CRF and EAT thereby suggesting that managing VAT by improving CRF could help in the prevention of cardiometabolic disorders related to excess EAT.

Background: Patients with ischemic heart failure (IHF) often undergo myocardial viability assessment to help determine the appropriate treatment strategy, whether revascularization or medical therapy. However, there is a lack of evidence regarding the optimal imaging modality for this purpose. The present study aimed to compare the clinical outcomes of IHF patients undergoing cardiac magnetic resonance (CMR) versus positron emission tomography (PET) for myocardial viability assessment. Methods: We enrolled patients >18 years with IHF and ejection fraction (EF) < 45% needing viability assessment. Exclusions included those with cardiac devices, significant medical conditions, recent ST segment myocardial infarction (<4 weeks), unsuitability for revascularization, or needing emergency revascularization/valve surgery. Patients were randomized to PET or CMR for viability detection. The primary endpoint was the composite of cardiac death, myocardial infarction, cardiac arrest, or cardiac re-hospitalization. Secondary endpoints evaluated the effect of imaging strategies on each composite component, including cardiac death. Results: Total of 116 patients were randomized to either the CMR group (n=60) or the PET group (n=56) at sites where both modalities were available. There were no significant differences between the CMR and PET groups in terms of average age (63.7±9.6 vs. 63.9±10.2), prevalence of male patients (90% vs. 89%), or NYHA class III or IV (40% vs. 38%). The mean EF was 25.5±7.9 in the CMR and 26.6±8.3 in the PET group, with a standardized difference of 0.264.Over a median (IQR) of 25.0 (15.3,29.6) months, the cumulative incidence rate (CIR) for the primary endpoint was 25.0% for CMR and 32.6% for PET (HR 0.74,CI 0.37-1.49,p=0.402).The CIR for cardiac death was 13.9% for CMR vs. 13.2% for PET (HR 1.12 (0.41,3.06,p=0.822)).(Fig.1) Conclusion: The result of this randomized cohort showed that among IHF patients who required a definition of viability, there were no significant differences in the incidence of important cardiac endpoints when either CMR or PET were used. Larger randomized clinical trials should be considered to confirm the current results.

Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic β-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.

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.

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.

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.