Canadian Cardiovascular Society/Canadian Women's Heart Health Alliance Clinical Practice Update on Myocardial Infarction With No Obstructive Coronary Artery Disease (MINOCA).

Myocardial infarction with no obstructive coronary artery disease (MINOCA) represents 6%-15% of all acute coronary syndromes, and women are disproportionately represented. MINOCA is an encompassing preliminary diagnosis, and emerging evidence supports a more expansive comprehensive diagnostic and therapeutic clinical approach. The current clinical practice update summarizes the latest evidence regarding the epidemiology, clinical presentation, and diagnostic evaluation of MINOCA. A cascaded approach to diagnostic workup is outlined for clinicians, for noninvasive and invasive diagnostic pathways, depending on clinical setting and local availability of diagnostic modalities. Evidence concerning the nonpharmacological and pharmacological treatment of MINOCA are presented and summarized according to underlying cause of MINOCA, with practical tips on the basis of expert opinion, outlining a real-life, evidence-based, comprehensive approach to management of this challenging condition.

Myosin Heavy Chain 7 (MYH7) Variant Associated Cardiovascular Disease: An Unusual Case of Heart Failure in a Young Male.

A 37-year-old male with type two diabetes presented to the hospital with new-onset heart failure and renal dysfunction. His left ventricular (LV) ejection fraction was less than 10%. Transthoracic echocardiography and cardiovascular magnetic resonance (CMR) imaging also revealed severe bicuspid aortic valve stenosis, dilated cardiomyopathy with LV hypertrophy, prominent LV trabeculations, and features suggestive of mild myocarditis with active inflammation. While myocarditis was suspected on CMR imaging, his mild degree of myocardial involvement did not explain the entirety of his clinical presentation, degree of LV dysfunction, or other structural abnormalities. An extensive work-up for his LV dysfunction was unremarkable for ischemic, metabolic, infiltrative, infectious, toxic, oncologic, connective tissue, and autoimmune etiologies. Genetic testing was positive for a myosin heavy chain 7 (MYH7) variant, which was deemed likely to be a unifying etiology underlying his presentation. The MYH7 sarcomere gene allows beta-myosin expression in heart ventricles, with variants associated with hypertrophic and dilated cardiomyopathies, congenital heart diseases, myocarditis, and excessive trabeculation (formerly known as left ventricular noncompaction). This case highlights the diverse array of cardiac pathologies that can present with MYH7 gene variants and reviews an extensive work-up for this unusual presentation of heart failure in a young patient.

Heterogeneity of coronary vascular function and myocardial oxygenation in women with angina and non-obstructive coronary artery disease.

AIMS: Women with angina and non-obstructive coronary artery disease (ANOCA) have a heightened risk for cardiovascular events, and the pathophysiology for ischaemic symptoms may be related to alterations in microvascular structure and function. We examined the use of breathing-enhanced oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) using vasoactive breathing manoeuvres to assess myocardial oxygenation in women with ANOCA. METHODS AND RESULTS: We recruited women (aged 40-65 years) from two sites in Canada who presented to healthcare with persistent retrosternal chest pain and found to have ANOCA, or without a history of cardiovascular disease. All participants were scanned using a clinical 3T MRI scanner, and OS-CMR images were acquired over a breath hold following paced hyperventilation to measure global and regional measurements of heterogeneity. Fifty-four women with ANOCA (age: 55 ± 6.2 years) and 48 healthy controls (age: 51.2 ± 4.8 years) were recruited. There was no significant difference in volume, function, mass, or global myocardial oxygenation between the two groups [mean %Δ in signal intensity (SI): 4.9 (±7.3) vs. 4.5 (±10.1), P = 0.82]. Women with ANOCA had higher regional variations in myocardial oxygenation in circumferential [median %Δ in SI: 5.1 (2.0-7.6) vs. 2.2 (1.4-3.5), P = 0.0004] and longitudinal directions [median %Δ in SI: 11.4 (5.4-16.7) vs. 6.0 (3.0-7.0), P = 0.001], which remained present in a multivariate model. CONCLUSION: Heterogeneous myocardial oxygenation may explain ischaemic symptoms without any associated epicardial obstructive coronary artery disease. Regional variations in myocardial oxygenation on OS-CMR could serve as an important diagnostic marker for microvascular dysfunction in women with ANOCA.

Automated Data Transformation and Feature Extraction for Oxygenation-Sensitive Cardiovascular Magnetic Resonance Images.

Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) is a novel, powerful tool for assessing coronary function in vivo. The data extraction and analysis however are labor-intensive. The objective of this study was to provide an automated approach for the extraction, visualization, and biomarker selection of OS-CMR images. We created a Python-based tool to automate extraction and export of raw patient data, featuring 3336 attributes per participant, into a template compatible with common data analytics frameworks, including the functionality to select predictive features for the given disease state. Each analysis was completed in about 2 min. The features selected by both ANOVA and MIC significantly outperformed (p < 0.001) the null set and complete set of features in two datasets, with mean AUROC scores of 0.89eatures f 0.94lete set of features in two datasets, with mean AUROC scores that our tool is suitable for automated data extraction and analysis of OS-CMR images.

Oestradiol implants for gender-affirming hormone therapy: an observational study of serum oestradiol levels and consumer survey.

BACKGROUND: Custom-compounded subcutaneous implants are being used widely in Australia for gender-affirming hormone therapy. However, there is no published literature regarding their use for this purpose. METHODS: Electronic medical records were audited for consecutive clients who received oestradiol implants April 2019-November 2022 in gender clinics held within Hunter New England Health District in New South Wales, Australia. Serum oestradiol levels were analysed for implant doses 50-200mg, and predicted oestradiol level was modelled following 100mg implant insertion. An electronic consumer survey was sent to a convenience sample of implant recipients. RESULTS: A total of 38 clients received 88 implants, with 100mg oestradiol implants being the most frequently used (68%). The median interval between insertion procedures was 270 (IQR 186-399) days. The median serum oestradiol levels following implant insertion, for all implants combined, were within the target range of 250-600pmol/L at 1-, 3-, 6-, 9- and 12-month time points. Following insertion of a 100mg implant, the estimated time to reach a predicted serum oestradiol of ≤250pmol/L was 4months after an initial implant, and 13months after subsequent implants. Seventeen consumer surveys were received from 28 invitations. All respondents had previous experience of oral and/or transdermal oestradiol use. Oestradiol implants were preferred due to ease of use, perceived effectiveness, and the belief that other methods were less safe or associated with intolerance and side effects. CONCLUSIONS: Oestradiol implants are effective in achieving target serum oestradiol levels over a sustained period. Further research with larger cohorts could identify the optimal dosage regimen.

5-fluorouracil-induced coronary vasospasm: A cardiovascular magnetic resonance imaging case report.

We report the case of a 45-year old male with metastatic colon cancer who presented with chest pain and transient diffuse ST-segment elevation on electrocardiogram after his third cycle of FOLFOX (folinic acid, fluorouracil, oxaliplatin). Initial transthoracic echocardiogram showed reduced left ventricular ejection fraction of 35% with mildly elevated troponins. Further investigations with cardiovascular magnetic resonance imaging demonstrated recovery of left ventricular function with evidence suggestive of coronary vasospasm. This case report will review the utility of cardiovascular magnetic imaging in the evaluation of underlying etiologies for myocardial injury in patients with low likelihood of obstructive coronary artery disease.

Association of abnormal electrocardiography response on dobutamine stress echocardiogram with longer-term major adverse cardiovascular events in women with symptoms of ischemic heart disease.

Background: Prior work demonstrates patients with positive (+) electrocardiogram (ECG) but negative (-) echocardiogram wall motion abnormalities (WMAs) on dobutamine stress echocardiography (DSE) testing have an elevated of major adverse cardiovascular events (MACEs). In this study, we aimed to evaluate the long-term prognosis of women with suspected ischemia with no obstructive coronary artery (INOCA) disease by utilizing core lab read DSE, specifically focusing on those with + ECG findings. Methods: Among women with signs and symptoms of myocardial ischemia undergoing clinically indicated coronary angiography enrolled in the Women's Ischemia Syndrome Evaluation (WISE) [1997-2001], a prospective cohort study, 99 underwent standardized DSE by site design. Women with positive DSE (n=17), defined as an increase in score based on wall motion scoring index were excluded except for akinetic to dyskinetic (n=10), providing 82 patients in this analysis. ECG was assessed by core laboratory and (+) ECG was defined as >1 mm ST change. Non-obstructive coronary artery disease (CAD) was assessed by core laboratory quantitative coronary angiography and defined as <50% epicardial stenosis. All-cause death follow-up was an average of 8 years, while adjudicated MACE [all-cause mortality, nonfatal myocardial infarction (MI), nonfatal stroke, heart failure hospitalization] was an average of 5.5 years. Comparisons among subject groups [i.e., (+) ECG and (-) ECG] were made using chi-square or Fisher's exact tests for categorical variables and t-test or Wilcoxon rank-sum test for continuous variables. Results: Demographic profile included a mean age 59±10 years; 55% had hypertension (HTN), 29% diabetes mellitus (DM), and 72% non-obstructive CAD. Overall, 9/82 women (11%) had (+) ECG in the absence of WMAs. There were significant differences in family history of CAD (P=0.009) and vasodilator (P=0.042) use between the (+) ECG and (-) ECG groups, but otherwise had no significant demographic or clinical differences. At longer-term follow up, patients with (+) ECG had higher risk of MACE [unadjusted hazard ratio (HR): 4.91, 95% confidence interval (CI): 1.83, 13.19, P=0.002]. Conclusions: Abnormal stress ECG findings on dobutamine stress testing with a negative DSE should be viewed as an indicator of longer-term risk in women with signs and symptoms of ischemia.

Clinical Practice Variations in the Management of Ischemia With No Obstructive Coronary Artery Disease.

Background Ischemia with no obstructive coronary artery disease is a condition associated with major adverse cardiovascular outcomes. To date, there are no specific American Heart Association or American College of Cardiology guidelines. The objective of this survey is to better understand the clinical practice and knowledge gaps that exist nationally. Methods and Results Participant-specific links for a survey with 11 questions and 3 reminders were sent between September and October 2020 to the American College of Cardiology CardioSurve Panel. The panel consist of randomly selected cardiologists (n=437) who represent the current profile of the American College of Cardiology US membership. The survey received a 30% response rate. Of the 172 respondents, 130 (76%) indicated that they have treated patients with ischemia with no obstructive coronary artery disease. Although the majority (69%) are generally confident in their ability to manage this condition, 1 of 3 report lack of confidence or are neutral. The American College of Cardiology/American Heart Association Chronic Stable Angina Guidelines are the most commonly used reference for treating ischemia with no obstructive coronary artery disease (81%), with most cardiologists wanting additional clinical guidance, such as randomized controlled trials (61%). More than 4 of 5 cardiologists rarely or never order advanced imaging modalities to assess coronary flow reserve. Approximately 2 of 3 of respondents frequently prescribe statins (68%), aspirin (66%), calcium channel blockers (63%), and ß blockers or α/ß blockers (55%). However, nearly 70% never prescribe angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Conclusions This survey demonstrates heterogeneity in the management of ischemia with no obstructive coronary artery disease among US cardiologists, identifies support for guideline development, and outlines knowledge gaps for research and education in the therapeutic management of this condition.

A collaborative model aligning adult sexual health and endocrine gender health services.

BACKGROUND: The Hunter New England (HNE) endocrinology and sexual health service commenced a co-located gender community clinic in 2018. This paper describes this novel model of service delivery, including the sociodemographics, clinical characteristics, and STI screening rates of trans and gender diverse (TGD) adults attending for gender-affirming hormone treatment (GAHT) and identifies patients accessing the broader skill set of both specialty services in 2018-19. METHODS: This study was a retrospective audit of medical records of all patients with initial consultations for GAHT at the endocrine and sexual health gender clinics from 1 January 2018 to 31 December 2019. A further data set included any adult TGD patient with any attendance, initial or subsequent, between 1 January 2018 and 31 December 2019. Patients with dual attendance at the endocrine gender clinic and sexual health service were further explored. RESULTS: Baseline sociodemographic data of participants were comparable in both gender clinics attended. Endocrinologists were more likely to use spironolactone for androgen blockade than the sexual health physician (77.8% vs 43.8%, P =0.0096), but prescribing patterns were otherwise similar. STI screening was more frequently performed in patients accessing GAHT through sexual health than endocrine gender clinics (35% vs 0.9%, P =0.00). Twenty patients (8.0%) had an attendance at both the sexual health and endocrine services and accessed STI screening, contraception, cervical screening, HIV pre- or post-exposure prophylaxis and estradiol implants. CONCLUSIONS: Co-located gender clinics staffed by endocrinology and sexual health physicians provide care for a similar patient population and facilitate access to GAHT, estradiol implants, STI screening, contraception, and cervical screening for the TGD population.

The effect of zinc supplementation on glucose homeostasis: a randomised double-blind placebo-controlled trial.

AIMS: The burden and health costs of Type 2 Diabetes Mellitus continue to increase globally and prevention strategies in at-risk people need to be explored. Previous work, in both animal models and humans, supports the role of zinc in improving glucose homeostasis. We, therefore, aimed to test the effectiveness of zinc supplementation on glycaemic control in pre-diabetic adults. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across 10 General Practitioner (GP) practices in NSW, Australia. The trial is known as Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD)Study. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4%, 39-46 mmol/mol) men and women (N = 98) were all assigned to a free state government telephone health coaching service (New South Wales Get Healthy Information and Coaching Service) and then randomised to either daily 30 mg zinc gluconate or placebo. Blood tests were collected at baseline, 1, 6 and 12 months for the primary outcomes (HbA1c, fasting blood glucose (FBG)); secondary outcomes included Homeostasis Model Assessment 2 (HOMA 2) parameters, lipids, body weight, height, waist circumference, blood pressure and pulse. RESULTS: The baseline-adjusted mean group difference at 6 months, expressed as treatment-placebo, (95% CI) was -0.02 (-0.14, 0.11, p = 0.78) for HbA1c and 0.17 (-0.07, 0.42; p = 0.17) for FBG, neither of which were statistically significant. There were also no significant differences between groups in any of the secondary outcomes. Zinc was well tolerated, and compliance was high (88%). CONCLUSION: We believe our results are consistent with other Western clinical trial studies and do not support the use of supplemental zinc in populations with a Western diet. There may still be a role for supplemental zinc in the developing world where diets may be zinc deficient. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.

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 .

Using the AUSDRISK score to screen for pre-diabetes and diabetes in GP practices: a case-finding approach.

OBJECTIVE: To identify the optimal AUSDRISK threshold score to screen for pre-diabetes and diabetes. METHODS: A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre-diabetes (5.7-6.4% or 39-47 mmol/mol), or normal (<5.7% or 39 mmol/mol). RESULTS: Of these patients, 9 (2%) had undiagnosed diabetes and 60 (15%) had pre-diabetes. A Receiver Operator Characteristic (ROC) curve was constructed to predict the presence of pre-diabetes and diabetes; the area under the ROC curve was 0.72 (95%CI 0.65-0.78) indicating modest predictive ability. The optimal threshold cut point for AUSDRISK score was 17 (sensitivity 76%, specificity 61%, + likelihood ratio (LR) 1.96, - likelihood ratio of 0.39) while the accepted cut point of 12 performed less well (sensitivity 94%, specificity 23%, +LR=1.22 -LR+0.26). CONCLUSIONS: The AUSDRISK tool has the potential to be used as a screening tool for pre-diabetes/diabetes in GP practices. A cut point of ≥17 would potentially identify 75% of all people at risk and three in 10 sent for further testing would be positive for prediabetes or diabetes. IMPLICATIONS FOR PUBLIC HEALTH: Routine case-finding in high-risk patients will enable GPs to intervene early and prevent further public health burden from the sequelae of diabetes.