John F. Beltrame

Background: In patients undergoing invasive coronary angiography for the investigation of angina, the management pathways for obstructive coronary artery disease (CAD) are well described, whereas the clinical and diagnostic journey of patients with ANOCA has largely been inferred, as there is limited quantitative data. Objective: To compare the journey of patients with ANOCA versus Obstructive CAD, particularly in relation to (i) clinical presentation and (ii) diagnostic assessment, (iii) 12 month patient-reported outcome measures (PROMs) and (iv) three year composite MACE. Methods: A total of 2,285 ANOCA and 4,087 Obstructive CAD consecutive patients were included from the CADOSA (Coronary Angiogram Database of South Australia) registry between 2012-2018. Results: At presentation for elective invasive angiography, the chest pain features and non-invasive ischemic markers were indistinguishable between patients with Obstructive CAD and ANOCA, although the latter were younger (67±11 vs. 61 ± 11 years, p<0.001), more likely to be female (27% vs. 58%, p<0.001) and have fewer traditional cardiac risk factors. However, following angiography (compared to those with Obstructive CAD) patients with ANOCA were less likely to attain a cardiac discharge diagnosis (100% vs. 22%) or receive anti-anginal therapy (76% vs. 57%), despite the same prevalence of persistent angina (weekly angina: 10% vs 11% over 12 months). Conclusions: Although the pre-angiography journey (symptoms & non-invasive ischemic investigations) of patients with Obstructive CAD and ANOCA is indistinguishable, the post-angiography journey is portrayed by a vast diagnostic and treatment gap in those with ANOCA, which needs to be addressed.

Background: Intracoronary acetylcholine provocative testing is the gold standard method for the assessment of epicardial and/or microvascular spasm, with the latter diagnosed when there is ACh-induced chest pain and ischaemic ECG changes in the absence of epicardial spasm. Whilst epicardial spasm can be visualised, microvascular spasm cannot and remains a presumed diagnosis. Methods: This paper describes a hydrodynamic model developed to calculate the epicardial and microvascular resistances for both pre- and post-ACh administration. The model is based on the concept of two resistances (epicardial and microvascular) located in a series arrangement. The epicardial resistance is obtained as a hydraulic resistance accounting for the friction resistance between the coronary blood flow and the arterial walls. The microvascular resistance is calculated by subtracting the epicardial resistance from the ratio of the pressure and flow measured using coronary guidewire-based techniques. Conclusions: This novel methodology provides key insights into the physiological characteristics of epicardial and microvascular spasm during ACh provocation testing. Further clinical validation is required to explore the clinical utility of this methodology.

Objectives: The diagnosis of coronary artery spasm (CAS) frequently requires invasive provocation testing, typically utilising acetylcholine (ACh). Although the left coronary artery (LCA) is routinely assessed as a part of the testing protocol, assessment of the right coronary artery (RCA) is often avoided since it requires the insertion of a temporary pacing wire. We sought to compare the prevalence of inducible CAS in the LCA and RCA, among patients with CAS undergoing multivessel spasm provocation testing with ACh. Methods: A local multi-institutional ANOCA (angina and non-obstructive coronary arteries) database was analysed, which included 316 patients with angina and suspected CAS who underwent provocation testing (single vessel n = 266, multivessel n = 50) with incremental bolus doses of intracoronary ACh (25, 50, 100 μg in the LCA; 25, 50 μg in the RCA). CAS was defined as >90% constriction of the epicardial coronary artery as assessed visually on coronary angiography. Results: In the 50 patients (55 ± 10 years, 77% female) who underwent multivessel spasm provocation testing, CAS was induced in 20 patients (40%), with ACh provoking CAS only in the LCA system in 45%, only in the RCA system in 35%, and both LCA/RCA in 20%. Conclusions: These findings demonstrate that assessing only the LCA may miss up to one-third of CAS cases. Therefore, it is essential to routinely evaluate the RCA, particularly when no inducible spasm is detected in the LCA.

Patients with angina and non-obstructive coronary arteries (ANOCA) or myocardial ischaemia with non-obstructive coronary arteries (INOCA) comprise a relatively large subgroup within those with ischaemic heart disease. Advances in the understanding of disease mechanisms, diagnostic tests and multidisciplinary care are improving awareness of the needs of affected individuals. However, practice variations and suboptimal management promulgate the health burden and increase health care resource consumption. Clinical standards represent a limited number of quality statements that describe the care patients should be offered by health professionals and providers for a specific clinical condition or defined clinical pathway in line with current best evidence. Clinical standards should address implementation of this evidence along with education of patients and healthcare professionals, multidisciplinary care networks, and research. In this consensus statement, we highlight contemporary evidence and stakeholder views, including clinicians and patients, to provide an international perspective for developing clinical standards for services involving ANOCA/INOCA patients. A clinical service for ANOCA/INOCA should "consider the whole patient" and provide a multidisciplinary, patient-centred service.

Background: Refractory vasospastic angina (VSA) includes patients with disabling angina despite maximally tolerated calcium channel blocker and nitrate therapy. Randomised clinical trial evidence confirms the efficacy of cilostazol in refractory VSA, yet its use in real-world clinical practice is limited. This study evaluated the impact of cilostazol therapy on patient-reported outcomes in patients with refractory VSA. Methods: Between June 2016 and May 2022, 15 consecutive refractory VSA patients were initiated on cilostazol (50 mg twice daily), with baseline and 3-month responses assessed via the Seattle Angina Questionnaire (SAQ). The primary outcome was a clinically significant reduction in angina frequency (i.e., >10-point improvement in SAQ angina frequency score) at 3 months. Results: A clinically significant reduction in angina frequency was reported in 13 patients (86%) at 3 months, with 3 (20%) becoming angina free. Moreover, over 3 months, median SAQ scores improved for angina frequency (25 [IQR 15, 46] to 75 [30, 82]), physical limitation (53 [44, 67] to 83 [56, 92]), and quality of life (17 [4, 29] to 50 [35, 58]). Additionally, a 54% reduction in angina-related emergency department presentations and 50% reduction in angina-related hospital admissions were noted. Minor medication-related adverse effects were experienced by 3 patients, with no serious adverse effects noted. Cilostazol was continued in 14 patients (93%) beyond the 3-month follow-up period. Conclusions: In patients with refractory VSA, cilostazol is well tolerated, improves patient-reported outcomes, reduces healthcare utilisation, and thus is an effective therapy in real-world clinical practice.