Protocol Variation in Functional Coronary Angiography Among Patients With Suspected Angina With Non-Obstructive Coronary Arteries: A Nationwide Snapshot of Current Practice Within Australia and New Zealand.

BACKGROUND: Functional coronary angiography (FCA) for endotype characterisation (vasospastic angina [VSA], coronary microvascular disease [CMD], or mixed) is recommended among patients with angina with non-obstructive coronary arteries. Whilst clear diagnostic criteria for VSA and CMD exist, there is no standardised FCA protocol. Variations in testing protocol may limit the widespread uptake of testing, generalisability of results, and expansion of collaborative research. At present, there are no data describing protocol variation across an entire geographic region. Therefore, we aimed to capture current practice variations in the approach to FCA to improve access and standardisation for diagnosis of coronary vasomotor disorders in Australia and New Zealand. METHOD: Between July 2022 and July 2023, we conducted a national survey across all centres in Australia and New Zealand with an active FCA program. The survey captured attitudes towards FCA and protocols used for diagnosis of coronary vasomotor disorders at 33 hospitals across Australia and New Zealand. RESULTS: Survey responses were received from 39 clinicians from 33 centres, with representation from centres within all Australian states and territories and both North and South Islands of New Zealand. A total of 21 centres were identified as having an active FCA program. In general, respondents agreed that comprehensive physiology testing helped inform clinical management. Barriers to program expansion included cost, additional catheter laboratory time, and the absence of an agreed-upon national protocol. Across the clinical sites, there were significant variations in testing protocol, including the technique used (Doppler vs thermodilution), order of testing (hyperaemia resistance indices first vs vasomotor function testing first), rate and dose of acetylcholine administration, routine use of temporary pacing wire, and routine single vs multivessel testing. Overall, testing was performed relatively infrequently, with very little follow-on FCA performed, despite nearly all respondents believing this would be clinically useful. CONCLUSIONS: This survey demonstrates, for the first time, variations in FCA protocol among testing centres across two entire countries. Furthermore, whilst FCA was deemed clinically important, testing was performed relatively infrequently with little or no follow-on testing. Development and adoption of a standardised national FCA protocol may help improve patient access to testing and facilitate further collaborative research within Australia and New Zealand.

How to Use Cardiac Magnetic Resonance Imaging in Myocardial Infarction With Nonobstructive Coronary Arteries.

The working diagnosis Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA) is being increasingly recognized with the common use of high-sensitivity troponins and coronary angiography, accounting for 5% to 10% of all acute myocardial infarction presentations. Cardiac magnetic resonance (CMR) imaging is pivotal in patients presenting with suspected MINOCA, mainly to delineate those with a nonischemic cause, for example, myocarditis and Takotsubo syndrome, from those with true ischemic myocardial infarction, that is, MINOCA. The optimal timing for CMR imaging in patients with suspected MINOCA has been uncertain and, until recently, not been examined prospectively. Previous retrospective studies have indicated that the diagnostic yield decreases with time from the acute event. The SMINC studies (Stockholm Myocardial Infarction with Normal Coronaries) show that CMR should be performed early in all patients with the working diagnosis of MINOCA, with the possible exception of patients who are clearly identified as having Takotsubo syndrome as determined by echocardiography. In addition to CMR imaging, other investigations of importance in selected patients may be pulmonary artery computed tomography to exclude pulmonary embolism, optical coherence tomography to identify plaque disruption, and acetylcholine provocation to identify coronary artery spasm. Imaging of patients with the working diagnosis MINOCA, which is centered on CMR together with supplemental investigations, results in a clear diagnosis in approximately three-quarters of the patients. This is a good example of personalized medicine, because a correct diagnosis will not only increase the satisfaction of the individual patient but also result in optimizing treatment without harming the patient.

Tandem lesions associate with angiographic progression of coronary artery stenoses.

Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56-73) and the median interval between angiograms was 2.1 years (IQR 1.2-3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04-4.63, p < 0.001) and circumflex artery stenosis location (OR 1.81, 95 % CI 1.21-2.7, p = 0.004) were associated with progressor status. Other lesion characteristics did not significantly impact progressor status or change in stenosis severity. Conclusion: Coronary lesions which have a downstream stenosis may be at increased risk of stenosis progression. Further research into the mechanistic basis of this finding is required, along with its implications for plaque vulnerability and clinical outcomes.

Anti-Anginal Efficacy of Zibotentan in the Coronary Slow-Flow Phenomenon.

BACKGROUND: Patients with coronary microvascular disorders often experience recurrent angina for which there are limited evidence-based therapies. These patients have been found to exhibit increased plasma levels of endothelin; thus, selective endothelin-A (Et-A) receptor blockers such as zibotentan may be an effective anti-anginal therapy in these patients. The study evaluated the impact of a 10 mg daily dose of zibotentan on spontaneous angina episodes in patients with the coronary slow-flow phenomenon who had refractory angina (i.e., experiencing angina at least three times/week despite current anti-anginal therapy). METHODS: Using a randomized, double-blind, placebo-controlled, crossover trial design with 4-week treatment periods, 18 patients (63.2 ± 9.9 years, 33% females) were recruited. The primary endpoint was angina frequency as measured by an angina diary, with secondary endpoints including nitrate consumption, angina duration/severity and the Seattle Angina Questionnaire (SAQ) domains. RESULTS: During the 4 weeks of therapy, angina frequency significantly improved with zibotentan therapy (placebo 41.4 (58.5) vs. zibotentan 29.2 (31.6), p < 0.05), and sublingual nitrate consumption significantly reduced (placebo 11.8 (15.2) vs. zibotentan 8.8 (12.9), p < 0.05. CONCLUSIONS: Zibotentan improved the frequency of spontaneous angina episodes and reduced sublingual nitrate consumption in patients unresponsive to standard anti-anginal therapy.

Angina and Non-Obstructive Coronary Artery (ANOCA) Patients with Coronary Vasomotor Disorders.

Angina and Non-Obstructive Coronary Artery (ANOCA) patients often lack a clear explanation for their symptoms, and are frequently discharged with the label of "unspecified chest pain", despite the availability of functional coronary angiography (provocative spasm and microvascular function testing) to identify potential underlying coronary vasomotor disorders. This study compared the outcomes of ANOCA patients with a coronary vasomotor disorder diagnosis post elective coronary angiography to patients discharged with unspecified chest pain. Using the CADOSA (Coronary Angiogram Database of South Australia) registry, consecutive symptomatic patients (n = 7555) from 2012 to 2018 underwent elective angiography; 30% had ANOCA (stenosis <50%). Of this cohort, 9% had documented coronary vasomotor disorders diagnosed, and 91% had unspecified chest pain. Patients with coronary vasomotor disorders were younger and had a similar female prevalence compared with those with unspecified chest pain. New prescriptions of calcium channel blockers and long-acting nitrates were more common for the coronary vasomotor cohort at discharge. In the 3 years following angiography, both groups had similar all-cause mortality rates. However, those with coronary vasomotor disorders had higher rates of emergency department visits for chest pain (39% vs. 15%, p < 0.001) and readmissions for chest pain (30% vs. 10%, p < 0.001) compared with those with unspecified chest pain. This real-world study emphasizes the importance of identifying high-risk ANOCA patients for personalized management to effectively address their symptoms.

Do Chest Pain Characteristics in Patients with Acute Myocardial Infarction Differ between Those with and without Obstructive Coronary Artery Disease?

The universal definition of acute myocardial infarction (MI) requires both evidence of myocardial injury and myocardial ischaemia. In MINOCA (MI with non-obstructive coronary arteries), patients must fulfil this MI criteria, but is their chest pain similar to those who have MI with obstructive CAD (MICAD)? This study compares prospectively collected chest pain features between patients with MINOCA and MICAD. Utilising the Coronary Angiogram Database of South Australia (CADOSA), consecutive MI patients were categorized as MINOCA or MICAD based on angiographic findings. Chest pain data were collected via direct patient interviews by trained staff members. Of 6811 consecutive patients fulfilling a clinical MI diagnosis, 411 (6.0%) were MINOCA, and 5948 MICAD. The MINOCA patients were younger, more often female and had less cardiovascular risk factors than those with MICAD. There were no significant differences in chest pain characteristics between the MINOCA and MICAD cohorts in relation to pain location, quality, associated symptoms, or duration. In conclusion, MINOCA patients have chest pain characteristics that are indistinguishable from MICAD patients, suggesting that their pain is ischaemic in nature. Thus, in the presence of positive myocardial injury markers, ischaemic chest pain fulfils the universal criteria for MI, despite the absence of obstructive coronary artery disease.

Coronary Spasm: Ethnic and Sex Differences.

Coronary spasm (CS), which may occur at the epicardial (focal or diffuse spasm) and/or microvascular (microvascular spasm) level, is a well-established cause of myocardial ischaemia, in particular in patients with anginal chest pain despite unobstructed coronary arteries. The diagnosis of CS can be confirmed during coronary angiography by an additional provocation test with vasoactive substances such as acetylcholine. Due to partially inconsistent data from large clinical studies, especially between Asian and white CS patients, ethnic differences concerning the prevalence and angiographic patterns of CS seem to exist. Furthermore, several studies in patients with coronary vasomotor disorders pointed towards differences among male and female CS patients. This article gives an overview of ethnic- and sex-related differences in patients with CS.

The Adelaide Score: An artificial intelligence measure of readiness for discharge after general surgery.

BACKGROUND: This study aimed to examine the performance of machine learning algorithms for the prediction of discharge within 12 and 24 h to produce a measure of readiness for discharge after general surgery. METHODS: Consecutive general surgery patients at two tertiary hospitals, over a 2-year period, were included. Observation and laboratory parameter data were stratified into training, testing and validation datasets. Random forest, XGBoost and logistic regression models were evaluated. Each ward round note time was taken as a different event. Primary outcome was classification accuracy of the algorithmic model able to predict discharge within the next 12 h on the validation data set. RESULTS: 42 572 ward round note timings were included from 8826 general surgery patients. Discharge occurred within 12 h for 8800 times (20.7%), and within 24 h for 9885 (23.2%). For predicting discharge within 12 h, model classification accuracies for derivation and validation data sets were: 0.84 and 0.85 random forest, 0.84 and 0.83 XGBoost, 0.80 and 0.81 logistic regression. For predicting discharge within 24 h, model classification accuracies for derivation and validation data sets were: 0.83 and 0.84 random forest, 0.82 and 0.81 XGBoost, 0.78 and 0.79 logistic regression. Algorithms generated a continuous number between 0 and 1 (or 0 and 100), representing readiness for discharge after general surgery. CONCLUSIONS: A derived artificial intelligence measure (the Adelaide Score) successfully predicts discharge within the next 12 and 24 h in general surgery patients. This may be useful for both treating teams and allied health staff within surgical systems.

Sex differences in treatment and outcomes amongst myocardial infarction patients presenting with and without obstructive coronary arteries: a prospective multicentre study.

Aims: Women have an increased prevalence of myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). Whether sex differences exist in the outcomes of patients with MI and obstructive coronary arteries (MIOCA) vs. MINOCA remains unclear. We describe sex-based differences in diagnosis, treatment, and clinical outcomes of patients with MINOCA vs. MIOCA. Methods and results: A large-scale cohort study of patients with ST/non-ST elevation MI undergoing coronary angiography (01/2015-12/2019). Patient demographics, diagnosis, prescribed discharge medications, in-hospital complications, and follow-up data were prospectively collected. A total of 13 202 participants were included (males 68.2% and females 31.8%). 10.9% were diagnosed with MINOCA. Median follow-up was 4.62 years. Females (44.8%) were as commonly diagnosed with MINOCA as males (55.2%), unlike the male preponderance in MIOCA (male, 69.8%; female, 30.2%). Less secondary prevention medications were prescribed at discharge for MINOCA than MIOCA. There was no difference in mortality risk between MINOCA and MIOCA [in-hospital: adjusted odds ratio (OR) 1.32, 95% confidence interval (CI) 0.74-2.35, P = 0.350; long term: adjusted hazard ratio (HR) 1.03, 95% CI 0.81-1.31, P = 0.813]. MINOCA patients had reduced mortality at long-term follow-up if prescribed secondary prevention medications (aHR 0.64, 95% CI 0.47-0.87, P = 0.004). Females diagnosed with MIOCA had greater odds of in-hospital and 1-year mortality than males (aOR 1.50, 95% CI 1.09-2.07, P = 0.014; aHR 1.18, 95% CI 1.01-1.38, P = 0.048). Conclusion: MINOCA patients have similar mortality rates as MIOCA patients. MINOCA patients were less likely than those with MIOCA to be discharged with guideline-recommended secondary prevention therapy; however, those with MINOCA who received secondary prevention survived longer. Females with MIOCA experienced higher mortality rates vs. males.

Role of Cardiac Magnetic Resonance Imaging and Troponin T in Definitive Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA).

BACKGROUND: It is unknown whether the degree of high-sensitivity troponin T (hsTropT) elevation in patients with suspected myocardial infarction without obstructive coronary arteries (MINOCA) presentations can help predict the likelihood of an abnormal cardiac magnetic resonance (CMR) scan. In this study we describe the diagnostic utility of CMR in patients with MINOCA and assesses the effect of peak hsTropT levels at presentation on CMR diagnostic yield. METHODS: Records of consecutive patients (n = 1407) referred for CMR at a tertiary referral hospital between January 2016 and September 2021 were reviewed. A total of 70 patients met the criteria of MINOCA including ischemic chest pain, elevated peak hsTropT, and nonobstructive coronary artery disease (< 50% stenosis). The peak hsTropT levels within 72 hours of admission were identified. CMR images were generated using a 3.0 T Siemens scanner. Predictors of having an abnormal CMR were evaluated. RESULTS: CMR established a diagnosis in 71% (n = 50) of patients, with the most common CMR diagnosis being myopericarditis (n = 27; 39%). Time to CMR was an independent predictor of a normal CMR scan (odds ratio, 0.98; 95% confidence interval, 0.97-0.999). Peak hsTropT had a high diagnostic accuracy for identifying patients with an abnormal CMR scan (area under the receiver operator characteristic curve, 0.81; P < 0.001). The optimal hsTropT cutoff was 166 ng/L, with 72% sensitivity and specificity. A troponin value ≥ 166 ng/L was independently predictive of an abnormal CMR scan (odds ratio, 4.76; 95% confidence interval, 1.32-17.11). CONCLUSIONS: HsTropT and early CMR imaging are independently predictive of an abnormal CMR scan in patients with MINOCA. Additionally, the use of a hsTropT cutoff provides incremental predictive value to clinical parameters and time to CMR scanning in determining an abnormal scan.

Lost in Translation: The Impact of Language Barriers on the Outcomes of Patients Receiving Coronary Artery Revascularization.

INTRODUCTION: Clear and effective communication is vital in discussions regarding coronary revascularization. Language barriers may limit communication in healthcare settings. Previous studies on the influence of language barriers on the outcomes of patients receiving coronary revascularization have produced conflicting results. The aim of this systematic review was to evaluate and synthesise the existing evidence regarding the effects of language barrier on the outcomes of patients receiving coronary revascularization. METHODS: A systematic review was conducted, including a search of the PubMed, EMBASE, Cochrane, and Google Scholar databases on 01/10/2022. The review was conducted in accordance with PRISMA guidelines. This review was also prospectively registered on PROSPERO. RESULTS: Searches identified 3983 articles of which a total 12 studies were included in the review. Most studies describe that language barriers result in delayed presentation, but not delays in treatment following hospital arrival with respect to coronary revascularization. The findings with respect to the likelihood of receiving revascularization have varied significantly; however, some studies have indicated that those with language barriers may be less likely to receive revascularization. There have been some conflicting results with respect to the association between language barrier and mortality. However, most studies suggest that there is no association with increased mortality. In studies that evaluated length of stay variable results have been reported based on geographical location. Namely Australian studies have suggested no association between language barrier and length of stay, but Canadian studies support an association. Language barriers may also be associated with readmissions following discharge, and major adverse cardiovascular and cerebrovascular events (MACCE). CONCLUSION: This study demonstrates that patients with language barriers may have poorer outcomes from coronary revascularization. Future interventional studies will be required to consider the sociocultural context of patients with language barriers, and may be targeted at timepoints including prior to, during, or after hospitalisation for coronary revascularization. Further examination of the adverse health outcomes of those with language barriers in fields outside of coronary revascularization are required in view of the stark inequities identified in this field.

Regional differences in percutaneous coronary intervention outcomes in STEMI patients with diabetes: The Asia-Pacific evaluation of cardiovascular therapies (ASPECT) collaboration.

BACKGROUND: Diabetes is associated with poorer outcomes and increased complication rates in STEMI patients undergoing percutaneous coronary intervention (PCI). Data are notably lacking in the Asia-Pacific region. We report the overall association of Diabetes with clinical characteristics and outcomes in STEMI patients undergoing PCI across the Asia-Pacific, with a particular focus on regional differences. METHODOLOGY: The Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration consists of data from various PCI registries across Australia, Hong Kong, Singapore, Malaysia, Indonesia and Vietnam. Clinical characteristics, lesion characteristics, and outcomes were provided for STEMI patients. Key outcomes included 30-day overall mortality and major adverse cardiovascular events (MACE). RESULTS: A total of 12,144 STEMI patients (mean(SD) age 59.3(12.3)) were included, of which 3912 (32.2%) had diabetes. Patients with diabetes were likely to have a higher baseline risk profile, poorer clinical presentation, and more complex lesion patterns (all p < 0.05). Across all regions, patients with diabetes had a higher rate of 30-day mortality and MACE (all p < 0.05). After multivariable adjustment, diabetes was significantly associated with both increased 30-day mortality (9.6%vs 5.5%, OR 1.79 [95% CI 1.40-2.30]) and MACE (13.3% vs 8.6%, R 1.73 [1.44-2.08]). The association between diabetes and 30-day MACE varied by region (pinteraction = 0.041), with the association (OR) ranging from 1.34 [1.08-1.67] in Malaysia, to 2.39 [1.66-3.45] in Singapore. CONCLUSIONS: Diabetes portends poorer clinical outcomes in STEMI patients undergoing PCI in the Asia-Pacific with regional variations noted. The development of effective preventative measures and interventional strategies targetted at this high-risk group is crucial.

Prognostic association of plasma NT-proBNP levels in patients with microvascular angina -A report from the international cohort study by COVADIS.

BackgroudThe aim of this study was to assess the prognostic association of plasma levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) with clinical outcomes of patients with microvascular angina (MVA). Methods: In this international prospective cohort study of MVA by the Coronary Vasomotor Disorders International Study (COVADIS) group, we examined the association between plasma NT-proBNP levels and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. Results: We examined a total of 226 MVA patients (M/F 66/160, 61.9 ± 10.2 [SD] yrs.) with both plasma NT-proBNP levels and echocardiography data available at the time of enrolment. The median level of NT-proBNP level was 94 pg/ml, while mean left ventricular ejection fraction was 69.2 ± 10.9 % and E/e' 10.7 ± 5.2. During follow-up period of a median of 365 days (IQR 365-482), 29 MACEs occurred. Receiver-operating characteristics curve analysis identified plasma NT-proBNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-proBNP level ≥ 78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95 % confidence interval (CI)] 3.11[1.14-8.49], P = 0.001). Accordingly, Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-proBNP ≥ 78 (log-rank test, P < 0.03). Finally, a significant positive correlation was observed between plasma NT-proBNP levels and E/e' (R = 0.445, P < 0.0001). Conclusions: These results indicate that plasma NT-proBNP levels may represent a novel prognostic biomarker for MVA patients.

Management of vasospastic angina.

Vasospastic angina is a well-established cause of chest pain that is caused by coronary artery spasm. It can be clinically diagnosed during a spontaneous episode by documenting nitrate-responsive rest angina with associated transient ischaemic ECG changes but more often requires provocative coronary spasm testing with acetylcholine during coronary angiography. Vasospastic angina may result in recurrent episodes of angina (including nocturnal angina), which can progress on to major adverse cardiac events. Calcium channel blockers are first-line therapy for this condition, given their anti-anginal and cardioprotective benefits. Despite an established diagnostic and therapeutic management pathway for vasospastic angina, this diagnosis is often overlooked in patients presenting with chest pain. Thus, there is need for increased clinical awareness of vasospastic angina to improve outcomes in affected patients.

Transdiagnostic Cognitive-Behavioral Therapy for Depression and Anxiety Disorders in Cardiovascular Disease Patients: Results From the CHAMPS Pilot-Feasibility Trial.

Objective: The aim of the Cardiovascular Health in Anxiety and Mood Problems Study (CHAMPS) is to pilot the Unified Protocol (UP) for the transdiagnostic treatment of depression and anxiety disorders in patients recently hospitalized for cardiovascular diseases (CVDs) and evaluate the feasibility. Methods: The present study is a controlled, block randomized pragmatic pilot-feasibility trial incorporating qualitative interview data, comparing UP (n = 9) with enhanced usual care (EUC, n = 10). Eligible trial participants had a recent CVD-cause admission and were above the severity threshold for depression or anxiety denoted by Patient Health Questionnaire (PHQ-9) total scores ≥10 and/or Generalized Anxiety Disorder (GAD-7) total scores ≥7 respectively on two occasions, and met criteria for one or more depression or anxiety disorders determined by structured clinical interview. Study outcomes were analyzed as intention-to-treat using linear mixed models and qualitative interview data were analyzed with content analysis. Results: Quantitative and qualitative measured indicated acceptability of the transdiagnostic CBT intervention for CVD patients with depression or anxiety disorders. Satisfaction with UP was comparable to antidepressant therapy and higher than general physician counseling. However, there were difficulties recruiting participants with current disorders and distress on two occasions. The UP was associated with a reduction in total number of disorders determined by blinded raters. Linear mixed models indicated that a significantly greater reduction in anxiety symptoms was evident in the UP group by comparison to the EUC group (GAD-7, p between groups = 0.011; Overall Anxiety Severity and Impairment Scale, p between groups = 0.013). Results favored the UP group by comparison to EUC for change over 6 months on measures of physical quality of life and harmful alcohol use. There was no difference between the two groups on changes in depression symptoms (PHQ-9), stress, metacognitive worry beliefs, physical activity, or adherence. Discussion: In conclusion, this feasibility trial indicates acceptability of transdiagnostic CBT intervention for CVD patients with depression or anxiety disorders that is tempered by difficulties with recruitment. Larger trials are required to clarify the efficacy of transdiagnostic depression and anxiety disorder CBT in populations with CVDs and depressive or anxiety disorders. Clinical Trial Registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12615000555550, identifier: ACTRN12615000555550.