Angina Pectoris

BackgroundPercutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina.ResultsA total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; PConclusionsAmong patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.).

Ischemic heart disease remains one of the leading causes of death and disability worldwide. However, most patients referred for a noninvasive computed tomography coronary angiogram (CTA) or invasive coronary angiogram for the investigation of angina do not have obstructive coronary artery disease (CAD). Approximately two in five referred patients have coronary microvascular disease (CMD) as a primary diagnosis and, in addition, CMD also associates with CAD and myocardial disease (dual pathology). CMD underpins excess morbidity, impaired quality of life, significant health resource utilization, and adverse cardiovascular events. However, CMD often passes undiagnosed and the onward management of these patients is uncertain and heterogeneous. International standardized diagnostic criteria allow for the accurate diagnosis of CMD, ensuring an often overlooked patient population can be diagnosed and stratified for targeted medical therapy. Key to this is assessing coronary microvascular function-including coronary flow reserve, coronary microvascular resistance, and coronary microvascular spasm. This can be done by invasive methods (intracoronary temperature-pressure wire, intracoronary Doppler flow-pressure wire, intracoronary provocation testing) and non-invasive methods [positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), transthoracic Doppler echocardiography (TTDE), cardiac computed tomography (CT)]. Coronary CTA is insensitive for CMD. Functional coronary angiography represents the combination of CAD imaging and invasive diagnostic procedures.

BackgroundAngina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy.MethodsPatients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFRResultsEighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; PP=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549).ConclusionsAmong phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.

IntroductionClonal haematopoiesis of indeterminate potential (CHIP) has been reported to increase the risk of various diseases, including cardiovascular diseases (CVDs). In contrast, a newly published study suggests that CHIP itself may not directly contribute to the risks of CVDs or other age-related conditions. CHIP could also serve as a protective factor against certain diseases, such as Alzheimer's disease. However, protective effects of CHIP against CVDs have rarely been investigated.ObjectivesTo demonstrate the associations with CHIP and lower angina pectoris (AP) risk especially unstable angina pectoris (UAP), and explore potential mechanisms.MethodsThis study was carried out based on UK Biobank cohort. General linear models adjusted for covariates were used to detect associations between CHIP and AP. Propensity score matching models were used for validation. Mendelian randomization was utilized for causality inference. Mediation analysis was conducted to explore underlying mechanisms of cytokines level.ResultsIn covariate models, large overall CHIP was associated with reduced AP and UAP risk. Large TET2 CHIP reduced AP and UAP risk. Propensity score matching models confirmed that large TET2 CHIP protected against AP and UAP. Mendelian randomization supported the effects of large TET2 CHIP against UAP. Large TET2 CHIP was linked to increased IL-1β levels, with IL-1β mediating the protection against UAP.ConclusionsCHIP protected against AP, with large TET2 CHIP specifically protecting against UAP. Elevated IL-1β levels might mediate this effect via plaque stabilization.