Invasive Endotyping in Patients With Angina and No Obstructive Coronary Artery Disease: A Randomized Controlled Trial.

BACKGROUND: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries. METHODS: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 µg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes. RESULTS: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P<0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P<0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P=0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P=0.013). CONCLUSIONS: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890.

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study.

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). OBJECTIVES: Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. DESIGN: A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. VALUE: CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population.

Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

BACKGROUND: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. METHODS/DESIGN: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. DISCUSSION: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01149590.

Malignant vasovagal syncope.

UNLABELLED: We report the case of a 21-year-old male whose frequent episodes of loss of consciousness in the dental surgery culminated in the postponement of treatment, pending further investigation. The patient was referred to a cardiologist and submitted to head-up tilt testing, which evoked prolonged asystole, associated with loss of consciousness and mild generalized twitching, confirming a diagnosis of malignant vasovagal syncope. Before dental treatment could be completed, the patient was successfully treated with disopyramide and dual-chamber pacemaker implantation. CLINICAL RELEVANCE: Dentistry can predispose patients to fainting (syncope or vasovagal episode) owing to fear, pain, unusual sights and smells, anxiety, fatigue and fasting, so knowledge of extreme forms of this response are of relevance.

TIMI Risk Score predicts early readmission.

AIM: To assess if the TIMI Risk Score could predict early readmission. PARTICIPANTS: 869 consecutive admissions to a Scottish district general hospital with suspected acute coronary syndrome. METHODS: A computerised clinical information system was interrogated to verify readmission. Area under the receiver operator characteristic curve and chi-square test for trend between TIMI Risk Score and readmission rate were calculated. RESULTS: Median follow up was 73 days. There was a strong association between TIMI Risk Score and readmission rate (chi-square test for trend, p<0.001), with an area under the receiver operator characteristic curve of 0.60 (95% C.I. 0.55-0.65). CONCLUSION: The TIMI Risk Score can predict readmission. This study reinforces its utility as a tool for identifying patients more likely to benefit from aggressive intervention.

Age-dependent differences in presentation, risk factor profile, and outcome of suspected acute coronary syndrome.

OBJECTIVES: To compare the presenting complaint, risk factors, and outcome of suspected acute coronary syndrome (ACS) in those aged 65 and older with those of a younger cohort. DESIGN: Prospective observational cohort study. SETTING: A typical Scottish district general hospital covering a population of 150,000. PARTICIPANTS: Patients presenting with suspected ACS (N=869) over a 6-month period. MEASUREMENTS: Main presenting complaint and major risk factors including electrocardiogram (ECG) changes. Primary outcome measures were percutaneous coronary intervention, recurrent myocardial infarction, and death at 3-month follow-up. RESULTS: Four hundred seventy-seven (55%) were aged 65 and older. Older patients were less likely to present with chest pain and more likely to present with breathlessness or collapse. They had fewer major risk factors for heart disease. There was a higher proportion with ischemic ECG changes, elevated troponin, and major acute coronary events at follow-up. Older patients were less likely to be accepted for angiography even though they were more likely than the younger cohort to have significant coronary artery disease when angiography was performed (chi-square test, P<.01 for all above). CONCLUSION: Older patients with suspected ACS were more likely to present atypically and have worse outcomes than their younger counterparts, despite having fewer major risk factors. The results highlight the importance of age as a predictor of adverse outcome and suggest that clinicians need to ensure equitable access to angiography for older patients.

A randomised controlled trial of senior Lay Health Mentoring in older people with ischaemic heart disease: The Braveheart Project.

OBJECTIVE: to examine the effects and feasibility of educating and empowering older people with ischaemic heart disease using trained senior lay health mentors. DESIGN: randomised controlled trial with blinded evaluation. SETTING: Falkirk and District Royal Infirmary. PARTICIPANTS: inpatients and outpatients aged 60 or over attending secondary care with a diagnosis of angina or acute myocardial infarction. Three-hundred and nineteen entered and 289 completed exit assessments. The intervention group took part in mentoring groups for 1 year, meeting monthly for 2 hours, each led by two trained lay health mentors in addition to standard care. MAIN OUTCOME MEASURES: primary outcome measures were changes in coronary risk factors, medication usage and actual use of secondary care health services. Secondary outcomes were total and cardiovascular events; changes in medication compliance, non-medical support requirement, health status and psychological functioning, and social inclusion. RESULTS: there were significant improvements in a reported current exercise score (mean +0.33, +0.02 to +0.52), in the average time spent walking per week by 72 minutes (+1 to +137 minutes), and in the SF36 Physical Functioning Score (+6.1, +2.4 to +9.5). There was a 1.0% reduction in total fat (95% CI -3.0% to -0.6%) and a 0.6% reduction in saturated fat (95% CI -1.5% to -0.03%). The intervention group showed reduced outpatient attendance for coronary heart disease (-0.25 appointments, -0.61 to -0.08). Attendance rates were high. Socio-economic grouping did not affect participation. CONCLUSIONS: Lay Health Mentoring is feasible, practical and inclusive, positively influencing diet, physical activity, and health resource utilisation in older subjects with ischaemic heart disease without causing harm.