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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Coronary functional testing to formally diagnose coronary microvascular dysfunction (CMD) reduces cardiovascular events and alleviates angina. This study aims to investigate the extensive and complex journey that patients with CMD undergo, from the onset of chest pain to eventual diagnosis. Data from the Coronary Microvascular Disease Registry (CMDR) were analyzed, including information on the date of first documentation of chest pain, number of non-invasive and invasive tests the patient underwent, emergency department visits, and hospitalizations. In addition, we estimated the total cost per patient. A total of 61 patients with CMD diagnosis were included in this analysis. Most patients in our cohort were older than 50 years of age. The median time from initial chest pain symptoms to diagnosis was 0.62 (interquartile range [IQR]: 0.06–2.96) years. During this period, patients visited the emergency department a median of 1.0 (IQR: 0.0–2.0) times. Diagnostic tests included 3.0 (IQR: 2.0–6.0) electrocardiograms, 3.0 (IQR: 0.0–6.0) high-sensitivity troponin tests, and 1.0 (IQR: 1.0–2.0) echocardiograms. Prior to diagnosis of CMD, 13 (21.3 %) patients had left heart catheterization without coronary functional testing. Non-invasive testing for ischemia was conducted in 43 (70.5 %) patients. Alternative non-cardiac diagnoses were given to 11 (18.0 %) patients during the diagnostic process, with referrals made to gastroenterology for 16 (26.2 %) and pulmonology for 10 (16.4 %) patients. The cost was almost $2000/patient. Timely identification of CMD offers promising opportunities for prompt symptom alleviation, accompanied by reduced visits to the emergency department, cardiovascular testing, invasive medical procedures, and consequently reduced healthcare expenses. • Angina pectoris impacting millions of individuals around the world • Coronary microvascular dysfunction (CMD) is a known etiology to cause angina. • This study reveals the journey of CMD patients from chest pain to diagnosis. • Healthcare providers must improve CMD awareness and understanding. • Further research is crucial to optimize CMD management. [ABSTRACT FROM AUTHOR]

Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug–drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A 60-year-old man with dermatomyositis who was taking 3 mg/day TAC contracted COVID-19. The patient started oral NMV/RTV therapy, and he was admitted to the hospital after 4 days because of chest pain and AKI. On day 5, his blood TAC level increased markedly to 119.8 ng/mL. RFP 600 mg was administered once daily for 3 days, and his blood TAC level decreased to the therapeutic range of 9.6 ng/mL on day 9, leading to AKI improvement. Transient complete atrioventricular block and nonsustained ventricular tachycardia were present during chest pain. In the coronary spasm provocation test, complete occlusion was observed in the right coronary artery, leading to a diagnosis of VSA. VSA and AKI are possible side effects of high blood TAC levels caused by DDI, and attention should be paid to cardiovascular side effects such as VSA and AKI associated with increased blood levels of TAC when it is used together with NMV/RTV. When blood levels of TAC increase, oral RFP can rapidly decrease TAC blood levels and potentially reduce its toxicity. [ABSTRACT FROM AUTHOR]

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology. • Angina pectoris may arise from obstructive CAD or in the absence of significant CAD. • Functional mechanisms may be involved in determining angina both in obstructive CAD and in ischemia with nonobstructed coronary arteries. • Revascularization and medical therapy play complementary roles in achieving optimal outcomes for patients with angina. • Management of angina is shifting toward a more personalized approach, moving away from the traditional one-size-fits-all strategy. [ABSTRACT FROM AUTHOR]

Administrative healthcare databases can be utilised for research. The accuracy of the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification (ICD-10-AM) coding of cardiovascular conditions in New Zealand is not known and requires validation. International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification coded discharges for acute coronary syndrome (ACS), heart failure (HF) and atrial fibrillation (AF), in both primary and secondary diagnostic positions, were identified from four district health boards between 1 January 2019 and 31 June 2019. A sample was randomly selected for retrospective clinician review for evidence of the coded diagnosis according to contemporary diagnostic criteria. Positive predictive values (PPVs) for ICD-10-AM coding vs clinician review were calculated. This study is also known as All of New Zealand, Acute Coronary Syndrome–Quality Improvement (ANZACS–QI) 77. A total of 600 cases (200 for each diagnosis, 5.0% of total identified cases) were reviewed. The PPV of ACS was 93% (95% confidence interval [CI] 89%–96%), HF was 93% (95% CI 89%–96%) and AF was 96% (95% CI 92%–98%). There were no differences in PPV between district health boards. PPV for ACS were lower in Māori vs non-Māori (72% vs 96%; p=0.004), discharge from non-Cardiology vs Cardiology services (89% vs 96%; p=0.048) and ICD-10-AM coding for unstable angina vs myocardial infarction (81% vs 95%; p=0.011). PPV for HF were higher in the primary vs secondary diagnostic position (100% vs 89%; p=0.001). The PPVs of ICD-10-AM coding for ACS, HF, and AF were high in this validation study. ICD-10-AM coding can be used to identify these diagnoses in administrative databases for the purposes of healthcare evaluation and research. [ABSTRACT FROM AUTHOR]

In stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in fact, angina. This study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI). ORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from −10 (placebo replicated the symptom more than balloon occlusion) to +10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI. Fifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95% credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95% credible interval: 0.71-1.99), Pr (difference) >99.9%. Similarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of Angina Assessment Before Revascularization [ORBITA-STAR]; NCT04280575) [Display omitted] [ABSTRACT FROM AUTHOR]

Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996–2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195). Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls. [ABSTRACT FROM AUTHOR]

The percutaneous management of chronic total occlusions (CTO) is a well-established sub-specialty of Interventional Cardiology, requiring specialist equipment, training, and techniques. The heterogeneity of approaches in CTO has led to the generation of multiple algorithms to guide operators in their management. The evidence base for management of CTOs has suffered from inconsistent descriptive and quantitative terminology in defining the nature of lesions and techniques utilised, as well as seemingly contradictory data about improvement in ventricular function, symptoms of angina, and mortality from large-scale registries and randomised controlled trials. Through this review, we explore the history of CTO management and its supporting evidence in detail, with an outline of limitations of CTO-percutaneous coronary intervention and a look at the future of this growing field within cardiology. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent assessment of myocardial perfusion and regional myocardial blood flow (MBF) of the left ventricle in absolute terms in milliliters per gram per minute (mL/g/min). The non-invasive quantification of MBF during pharmacologically induced hyperemia, at rest, and corresponding myocardial flow reserve (MFR) opens a new avenue for the identification and characterization of classical or endogen type of coronary microvascular dysfunction (CMD) as functional substrate for microvascular angina in patients with non-obstructive coronary artery disease (CAD) and/or no CAD at all. Further, PET-MBF quantification expands the scope of conventional myocardial perfusion imaging from the identification of advanced, and flow-limiting, epicardial CAD to early stages of atherosclerosis and/or CMD. Adding MBF assessment to myocardial perfusion may also reliably unravel diffuse ischemia owing to significant left main stenosis and/or multivessel CAD, commonly confirmed by peak stress transient ischemic cavity dilation of the left ventricle during maximal vasomotor stress compared to rest on gated PET images. Owing to high spatial and contrast resolution in conjunction with photon-attenuation free myocardial perfusion PET images, PET is preferentially used for CAD detection in advanced obesity and women with pronounced breast habitus. With increasing clinical use of cardiac PET perfusion and MBF assessment, individualized, and image-guided cardiovascular treatment decisions in CAD patients is likely to ensue, while its translation into improved cardiovascular outcome remains to be investigated. [ABSTRACT FROM AUTHOR]

The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients. The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making. One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status). Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making. In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522) [Display omitted] [ABSTRACT FROM AUTHOR]

Type 4a myocardial infarction (T4aMI), defined as myocardial injury associated with percutaneous coronary intervention (PCI), is associated with a poor prognosis and there is conflicting evidence regarding the effectiveness of remote ischaemic conditioning (RIC) in its prevention. This review aimed to determine the effect of RIC on stable and unstable angina patients. A systematic review was conducted in PubMed and Central database. Outcome measures were: changes in peak troponin, creatine kinase myocardial band (CKMB), C-reactive protein (CRP) level, incidence of T4aMI, and major adverse cardiovascular event (MACE). Data were meta-analysed and reported as standardised mean difference (SMD) and odds ratio (OR). Risk of bias was assessed with the Risk of Bias 2 (RoB2) tool. Fifteen studies with no significant risk of bias were included. Peak troponin level was reduced in the RIC group, particularly after excluding a study with low statin use, while CKMB and CRP levels resulted in a non-significant SMD between the groups. The incidence of T4aMI was significantly lower in the intervention group (OR 0.714; p=0.026); this finding was also seen in subgroups of elective PCI, pre-conditioning, and high statin use. Incidence of MACE also only reached statistically significant protective effects with OR <1 in similar subgroups. No substantial heterogeneity was found and the funnel plot did not show publication bias. Remote ischaemic conditioning in elective PCI patients has been proven to be potentially beneficial in reducing peak troponin levels and risk of T4aMI and MACE. [ABSTRACT FROM AUTHOR]

A 34-year-old man with a history of Kawasaki disease had been experiencing chest pain at rest since middle school. Multidetector-row computed tomography showed no aneurysm formation; however, the right coronary artery had an anomalous origin with moderate stenosis. Invasive coronary angiography revealed moderate right coronary artery stenosis with a fractional flow reserve of 0.97. Finally, with a positive acetylcholine provocation test and elevated index of microvascular resistance, the patient was diagnosed with microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries. This is the first reported case of both microvascular and epicardial vasospastic angina after Kawasaki disease. In patients with a history of Kawasaki disease, even those without cardiac sequelae, coronary endothelial and microvascular dysfunctions should be taken into consideration. We report the first case of both microvascular and epicardial vasospastic angina in the endotypes of ischemia with nonobstructive coronary arteries after Kawasaki disease. Coronary endothelial and microvascular dysfunctions should be taken into consideration in patients with a history of Kawasaki disease, even those without cardiac sequelae. [ABSTRACT FROM AUTHOR]

The optimal surveillance strategy after percutaneous coronary intervention (PCI) for high-risk patients with multivessel or left main coronary artery disease (CAD) remains uncertain. This study aims to determine the prognostic role of routine functional testing in patients with multivessel or left main CAD who underwent PCI. The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial randomized high-risk PCI patients to routine functional testing at 1 year or standard care alone during follow-up. This analysis focused on participants with multivessel or left main CAD. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Among 1,706 initially randomized patients, 1,192 patients with multivessel (n = 833) or left main (n = 359) were identified, with 589 in the functional testing group and 603 in the standard care group. Two-year incidences of primary outcome were similar between the functional testing group and the standard care group (6.2% vs 5.7%, respectively; HR: 1.09; 95% CI: 0.68-1.74; P = 0.73). This trend persisted in both groups of multivessel (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.62-1.89; P = 0.78) and left main disease (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.46-2.56; P = 0.85) (P for interaction = 0.90). Routine surveillance functional testing was associated with increased rates of invasive angiography and repeat revascularization beyond 1 year. In high-risk patients with multivessel or left main CAD who underwent PCI, there was no incremental clinical benefit from routine surveillance functional-testing compared with standard care alone during follow-up. (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention [POST-PCI]; NCT03217877) [Display omitted] [ABSTRACT FROM AUTHOR]

In FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), during a median follow-up of 2.2 years, risk reduction for major adverse cardiovascular event with evolocumab was greater in patients with multivessel disease (MVD). The FOURIER Open-Label Extension (FOURIER-OLE) provides an additional median follow-up of 5 years. The purpose of this study was to assess the long-term benefit of evolocumab in patients with and without MVD. FOURIER randomized 27,564 patients to evolocumab vs placebo; 6,635 entered FOURIER-OLE. Patients with coronary artery disease were categorized based on the presence of MVD (≥40% stenosis in ≥2 large vessels). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; the key secondary endpoint was cardiovascular death, myocardial infarction, or stroke. Of 23,656 patients in FOURIER with coronary artery disease, 25.4% had MVD; 5,887 patients continued into FOURIER-OLE. The risk reduction with initial allocation to evolocumab tended to be greater in patients with MVD than in those without: 23% (HR: 0.77 [95% CI: 0.68-0.87]) vs 11% (HR: 0.89 [95% CI: 0.82-0.96]) for the primary and 31% (HR: 0.69 [95% CI: 0.59-0.81]) vs 15% (HR: 0.85 [95% CI: 0.77-0.94]) for the key secondary endpoints (P interaction = 0.062 and P interaction = 0.031, respectively). The magnitude of benefit tended to grow during the first several years, reaching 37% to 38% reductions in risk in patients with MVD and 23% to 28% reductions in risk in patients without MVD. Evolocumab reduced the rate of major adverse cardiovascular event in patients with and without MVD. The benefit tended to occur earlier and was larger in patients with MVD. However, the magnitude grew over time in both groups. These data support early initiation of intensive low-density lipoprotein cholesterol lowering both in patients with and without MVD. [Display omitted] [ABSTRACT FROM AUTHOR]

In the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous coronary intervention (PCI) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization and a conservative (CON) strategy of initial medical therapy. The authors analyzed separately the outcomes of INV patients treated with PCI or CABG. Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) was used. Among INV-CABG patients, primary outcome events occurred in 84 of 512 (16.4%) at a median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs. Among INV-PCI patients, primary outcome events occurred in 147 of 1,500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) occurred within 30 days after PCI, including 24 procedural MIs. In comparison, 352 of 2,591 CON patients (13.6%) had primary outcome events at a median follow-up of 3.2 years, 22 of which (6.3%) occurred within 30 days of randomization. The adjusted primary outcome risks were higher after both CABG and PCI within 30 days (HR: 16.25 [95% CI: 11.44-23.07] and HR: 2.99 [95% CI: 1.97-4.53]) and lower thereafter (0.63 [95% CI: 0.44-0.89] and 0.66 [95% CI: 0.53-0.82]). In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, owing to protocol-defined procedural MIs. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 ± 2.77 ng/100 mg tissue, n = 8 vs 0.24 ± 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry–positive area percentage: 2.88 ± 0.53 %, n = 22 vs 0.67 ± 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry–positive area percentage than those who would develop restenosis (n = 12) (2.32 ± 0.49 % vs 0.49 ± 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects. [Display omitted] • Intraplaque CRP is known to promote atherosclerosis, but pentraxin 3 may not. • Pentraxin 3 in plaque increases as atherosclerosis progresses. • Pentraxin 3 inhibited SMC proliferation and migration in vitro. • Flow chamber system study showed pentraxin 3 inhibits thrombus formation. • Intraplaque pentraxin 3 might have atheroprotective effects. [ABSTRACT FROM AUTHOR]

There is limited data comparing Coronary Computed Tomography Angiography (CCTA) versus the usual Standard of care (SOC) in patients with suspected stable coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis to compare CCTA versus SOC in patients with stable CAD. We searched multiple databases for randomized controlled trials (RCTs) comparing CCTA with SOC, which included various functional testing approaches for evaluating stable CAD. We used a random-effects model to calculate risk ratios (RRs) with 95 % confidence intervals (CIs). Outcomes included all-cause mortality, myocardial infarction (MI), hospitalization for unstable angina (UA), invasive angiography, revascularization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). We identified 6 RCTs with 19,881 patients with stable CAD, of which 9995 underwent CCTA, and 9886 underwent SOC. There were no significant differences between CCTA and SOC in terms of all-cause mortality (RR: 0.91; 95 % CI: 0.70–1.19; p = 0.50), MI (RR: 0.78; 95 % CI: 0.58–1.05; p = 0.11), hospitalizations for UA (RR: 1.20; 95 % CI: 0.95–1.51;p = 0.12), invasive angiography (RR: 0.71; 95 % CI: 0.32–1.61; p = 0.42), revascularization (RR:1.25; 95 % CI: 0.83–1.89; p = 0.29), PCI (RR: 1.20; 95 % CI: 0.78–1.85; p = 0.40), and CABG rates (RR: 0.89; 95 % CI: 0.530–1.49; p = 0.65). In patients with stable CAD, CCTA is associated with similar outcomes compared to the usual Standard of care. Given its potential to quickly rule out severe obstructive disease, its ability to provide non-invasive physiology and identify non-obstructive CAD with plaque information makes it an attractive addition to the available armamentarium to evaluate chest pain. • In patients with stable angina, CCTA was associated with similar rates of all-cause mortality, MI, CABG, hospitalization for UA, PCI, invasive angiography, and revascularization compared to standard of care. • Subgroup analyses comparing only CCTA vs stress testing were included, there was an increase in rates of CABG, downstream invasive angiography, PCIs, and revascularizations. However, an overall decrease in rates was seen when only CCTA and invasive angiography RCTs were subgroup analyzed. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

The prognostic significance of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS) according to prior myocardial infarction (MI) remains unclear. We aimed to investigate the association between OSA and long-term cardiovascular outcomes in ACS patients with or without prior MI. We prospectively recruited eligible 2160 ACS patients with portable sleep monitoring in Beijing Anzhen Hospital between June 2015 and January 2020. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/hour. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Among 1927 patients enrolled, 1014 (52.6%) had OSA and 316 (16.4%) had prior MI. During 2.9 (1.5, 3.6) years of follow-up, multivariate analysis showed that OSA was associated with 1.7 times the risk of MACCE in patients with prior MI (50 events [28.2%] vs 24 events [17.3%]; adjusted HR = 1.74, 95%CI 1.04–2.90, P = 0.034), but not in patients without prior MI group (177 events [21.1%] vs 138 events [17.8%]; adjusted HR = 1.19, 95%CI 0.94–1.51, P = 0.15). There was no significant interaction between prior MI and OSA for MACCE (interaction P = 0.14). OSA was independently associated with an increased risk of MACCE among ACS patients, particularly among ACS patients with prior MI. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS characterized by prior MI are warranted. [Display omitted] • This was a large prospective cohort study designed to determine the relationship between OSA and prognosis in ACS. • This study enrolled 1927 hospitalized patients, and with a mean follow-up up to 2.9 years (1.5, 3.6). • OSA was independently associated with an increased risk of MACCE among ACS patients, particularly among those with prior MI. [ABSTRACT FROM AUTHOR]

Refractory Angina (RA) is an increasingly common clinical diagnosis, in which patients unsuitable for further percutaneous or surgical procedures experience anginal symptoms, despite receiving optimal medical therapy. This clinical condition challenges the everyday activities and diminishes the quality of life of these patients. A wide variety of novel therapies for this type of angina are being investigated for clinical use. One of them is coronary sinus narrowing, which is performed as a percutaneous interventional procedure using catheter-delivered device, the Reducer. The device is implanted in the coronary sinus creating a physical narrowing and a pressure gradient in the sinus. This intervention improves the impaired blood flow in the ischemic regions of the heart leading to the relief of the anginal symptoms and, therefore, the overall clinical improvement of these patients. Several clinical trials have established both the safety and efficacy of the coronary sinus Reducer, while ongoing trials are aiming to further establish the procedure's safety and efficiency in both RA and other cardiovascular diseases, such as coronary microvascular dysfunction. This review aims to discuss the pathophysiology and the role of the coronary sinus Reducer in RA, the clinical trials documenting its safety and efficacy, as well as the future perspectives of this procedure among cardiovascular diseases. [Display omitted] • Coronary sinus narrowing is an interventional procedure creating a pressure gradient in the sinus • The increased blood backflow in the coronary system results to angina symptoms relief • Safety and efficay of Reducer in refractory angina is established. • Further research is needed in the settings of coronary microvascular dysfunction and heart failure. [ABSTRACT FROM AUTHOR]

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Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials. [Display omitted] • Comprehensive CFT is important to identify underlying causes of ANOCA. • Close follow-up is critical to monitor ANOCA symptoms, titrate medications, and modify other therapies. • Multicenter registries encourage standardization and collaboration and can advance our understanding of ANOCA. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-33 and its soluble receptor ST2 (sST2) play a crucial role in the immune response. sST2 has been approved by the Food and Drug Administration as a prognostic biomarker of mortality in chronic heart failure patients, however, the role of IL-33 and sST2 in atherosclerotic cardiovascular disease remains unclear. The aim of this study was to measure serum level of IL-33 and sST2 of patients at the onset of acute coronary syndrome (ACS) and 3 months after primary percutaneous revascularization. Forty patients were divided into ST segment elevation myocardial infarction (STEMI) group, non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) group. IL-33 and sST2 level were measured with ELISA. Additionally, IL-33 expression in peripheral blood mononuclear cells (PBMCs), was evaluated. All ACS patients had a significantly lower level of sST2 3 months after ACS as compared to the baseline (p ​< ​0.039). The STEMI patients had higher serum levels of IL-33 at the moment of ACS as compared to 3 months after the event, with an average decrease of 17.87 ​pg/ml (p ​< ​0.007). Conversely, sST2 serum levels were still high after 3 months following an ACS in STEMI patients. ROC curve demonstrated that increased IL-33 serum level could be STEMI predictor. The assessment of the baseline and dynamics of changes in IL-33 and sST2 concentrations in patients with ACS may be important for the diagnostic process and may help in understanding of how the immune mechanisms work at the moment of an ACS event. [Display omitted] [ABSTRACT FROM AUTHOR]

Intracoronary brachytherapy (ICB) has mainly been used to treat in-stent restenosis following percutaneous coronary intervention and was virtually abandoned about 20 years ago. However, patients treated with this strategy are still alive and some teams continue to perform this therapy. We aimed to investigate the very long-term clinical outcome of patients treated with ICB. A total of 173 consecutive patients who had been treated with ICB at a large tertiary referral centre between 1998 and 2003 were included. The primary endpoint of the study was all-cause mortality. The secondary endpoints were as follows: occurrence of major adverse cardiac events (MACE, defined as all-cause death, non-fatal myocardial infarction, or target vessel revascularization), cardiac death, and presence of angina at the end of follow-up. Patients' mean age at the time of ICB was 64 ± 10 years and 77 % were male. Restenosis (bare metal stent vs. balloon angioplasty) was the only indication for ICB. Unstable angina was present in 34 % of the patients. Follow-up was available for 166 patients. After a mean follow-up of 20 ± 1.3 years, 66 % of the patients had died (including 74 patients (67 %) with cardiac death). Cumulative MACE rate at 20 years was 96 %. Very long-term follow-up of patients with in-stent restenosis treated with ICB confirmed a high all-cause mortality rate mainly due to cardiac causes and MACEs. • A mean follow-up of 20 years is the longest assessed for intracoronary brachytherapy (ICB). • Long term high all-cause mortality after ICB was mainly due to cardiac death. • A high cumulative major adverse cardiac event (MACE) of 96 % was found at 20 years of follow up after ICB. [ABSTRACT FROM AUTHOR]

Diagnosis of acute myocardial infarction (AMI) requires a combination of elevated cardiac troponins, and clinical or echocardiographic evidence of coronary ischaemia. Identification of patients with a high likelihood of coronary plaque rupture (Type 1 myocardial infarction [MI]) is crucial as it is these patients for whom coronary intervention has been well-established to provide benefit and reduce subsequent coronary ischemic events. However, high-sensitivity cardiac troponin (hs-cTn) assays have increasingly identified patients with hs-cTn elevations not due to Type 1 MI where recommendations for ongoing care are currently limited. Understanding the profile and clinical outcomes for these patients may inform the development of an emerging evidence-base. Using two previously published studies (hs-cTnT study n=1,937, RAPID-TnT study n=3,270) and the Fourth Universal Definition of MI, index presentations of patients to South Australian emergency departments with suspected AMI, defined by high sensitivity cardiac troponin T (hs-cTnT) greater than the upper reference limit (14 ng/L) and without obvious corresponding ischaemia on electrocardiogram (ECG), were classified as either Type 1 MI (T1MI), Type 2 MI (T2MI), acute myocardial injury (AI), or chronic myocardial injury (CI). Patients with non-elevated hs-cTnT (defined as <14 ng/L) were excluded. Outcomes assessed included death, MI, unstable angina, and non-coronary cardiovascular events within 12 months. In total, 1,192 patients comprising 164 (13.8%) T1MI, 173 (14.5%) T2MI/AI, and 855 (71.7%) CI were included. The rate of death or recurrent acute coronary syndrome was greatest in patients with T1MI, but also occurred with moderate frequency in Type 2 MI/AI and CI (T1MI: 32/164 [19.5%]; T2MI/AI: 24/173 [13.1%]; CI:116/885 [13.6%]; p=0.008). Of all the deaths observed, 74% occurred among those with an initial index diagnostic classification of CI. After adjusting for age, gender and baseline comorbidities, the relative hazard ratios for non-coronary cardiovascular readmissions were similar across all groups: Type 2 MI/AI: 1.30 (95% confidence interval 0.99–1.72, p=0.062); CI: 1.10 (95% confidence interval 0.61–2.00, p=0.75). Non-T1MI accounted for the majority of patients presenting with elevated hs-cTnT without ischaemia on ECG. Patients with T1MI had the highest rates of death or recurrent AMI; however patients with T2MI/AI and CI experienced a substantial rate of non-coronary cardiovascular re-hospitalisations. [ABSTRACT FROM AUTHOR]

The impact of complete revascularization (CR) on angina-related health status (symptoms, function, quality of life) in chronic coronary disease (CCD) has not been well studied. Among patients with CCD randomized to invasive (INV) vs conservative (CON) management in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), we compared the following: 1) the impact of anatomic and functional CR on health status compared with incomplete revascularization (ICR); and 2) the predicted impact of achieving CR in all INV patients compared with CON. Multivariable regression adjusting for patient characteristics was used to compare 12-month health status after independent core laboratory-defined CR vs ICR in INV patients who underwent revascularization. Propensity-weighted modeling was then performed to estimate the treatment effect had CR or ICR been achieved in all INV patients, compared with CON. Anatomic and functional CR were achieved in 43.3% and 57.8% of 1,641 INV patients, respectively. Among revascularized patients, CR was associated with improved Seattle Angina Questionnaire Angina Frequency compared with ICR after adjustment for baseline differences. After modeling CR and ICR in all INV patients, patients with CR and ICR each had greater improvements in health status than CON, with better health status with CR than ICR. The projected benefits of CR were most pronounced in patients with baseline daily/weekly angina and not seen in those with no angina. Among patients with CCD in ISCHEMIA, health status improved more with CR compared with ICR or CON, particularly in those with frequent angina. Anatomic and functional CR provided comparable improvements in quality of life. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522) [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify whether the association of gait speed with the incidence of cardiovascular disease depends on baseline glycemic status. This retrospective observational cohort study used the Japan Medical Data Center Claims Database between 2005 and 2021 and analyzed 3,090,048 participants without a cardiovascular disease history. The median (IQR) age was 44 (37–53) years, and 1,755,205 of the participants (56.8%) were men. Information on gait speed was obtained from self-reported questionnaires in health checkups. Study participants were categorized according to HbA1c levels (<5.7%, 5.7–6.4%, and ≥6.5%). The primary endpoint was defined as a composite cardiovascular disease outcome that consists of heart failure, myocardial infarction, angina pectoris, and stroke. During the mean follow-up period of 1,120±857 days, 116,678 composite cardiovascular disease outcomes were documented. Self-reported fast gait speed was related to a lower risk of developing cardiovascular disease; this relationship was more pronounced with increasing HbA1c levels. Compared with slow gait speed, the hazard ratio (95% CI) of self-reported fast gait speed for cardiovascular disease was 0.935 (0.921–0.949) in participants with an HbA1c <5.7%, 0.911 (0.891–0.932) in participants with an HbA1c of 5.7–6.4%, and 0.846 (0.811–0.883) in participants with HbA1c ≥6.5% (p -value for interaction<0.001). The relationship of subjective gait speed with the risk of cardiovascular disease was amplified in individuals with prediabetes or diabetes mellitus, suggesting that maintaining exercise capacity could be more important in individuals with impaired glucose tolerance for preventing cardiovascular disease. [ABSTRACT FROM AUTHOR]

The Seattle Angina Questionnaire (SAQ-7) quantifies the impact of angina on patient functionality and quality of life. There is scarce data on the impact of social determinants and comorbidities on SAQ-7 in patients undergoing percutaneous coronary intervention (PCI) with planned staged PCI. Patients completed a SAQ-7 before each PCI. Multivariable regression analysis was performed to study the impact of social determinants, comorbidities, and procedural characteristics on SAQ-7 scores at index PCI and at the time of the staged PCI. 531 patients were studied. Female sex, non-White race, coronary artery bypass graft history (CABG), and chronic lung disease were associated with lower baseline SAQ-7 scores. Overall, SAQ-7 increased between index procedure and staged PCI (11.9 ± 23.4). Body mass index (BMI) and the treatment of bifurcation lesions were independently associated with improvement of SAQ-7 between PCIs. Post-intervention, neither sex nor race was independently associated with changes in SAQ-7 scores. Different disparities and comorbid factors affect SAQ-7 before and after PCI. After revascularization, sex and race were not independent predictors of SAQ-7 improvement. [Display omitted] • Different disparities and comorbid factors affect SAQ-7 before and after PCI. • Intervention of birfurcation lesions resulted in higher likelihood of improvement of the SAQ-7 score at the time of staged intervention. • After revascularization, sex and race were not independent predictors of SAQ-7 improvement. [ABSTRACT FROM AUTHOR]

Invasive assessments of microvascular function are rapidly becoming an integral part of physiological assessment in chronic coronary syndromes. We aimed to establish a reference range for Doppler flow velocity-derived hyperaemic microvascular resistance index (HMR) in a cohort of angina with no significant epicardial coronary obstruction (ANOCA) patients with no structural pathophysiological alterations in the coronary circulation. The reference population consisted of ANOCA patients undergoing invasive coronary vasomotor function assessment who had a coronary flow reserve (CFR) >2.5, and had either (1) tested negatively for spasm provocation (n = 12) or (2) tested positively with only angina at rest (n = 29). A reference range for HMR was established using a non-parametric method and correlations with clinical characteristics were determined using a spearman rank correlation analysis. In 41 patients median HMR amounted to 1.6 mmHg/cm/s [Q1, Q3: 1.3, 2.2 mmHg/cm/s]. The reference range for HMR that is applicable to 95% of the population was 0.8 mmHg/cm/s (90% CI: 0.8–1.0 mmHg/cm/s) to 2.7 mmHg/cm/s (90% CI: 2.6–2.7 mmHg/cm/s). No significant correlations were found between HMR and clinical characteristics. In this reference population undergoing invasive coronary vasomotor function testing, the 90% confidence interval of the HMR upper limit of normal ranges from 2.6 to 2.7 mmHg/cm/s. A > 2.5 mmHg/cm/s HMR threshold can be used to identify abnormal microvascular resistance in daily clinical practice. [Display omitted] • Increased HMR in the absence of epicardial stenoses is considered a surrogate marker of coronary microvascular pathology. • There was excellent correlation between HMR measurements obtained with or without a microcatheter. • A >2.5 mmHg/cm/s HMR threshold can be used to identify abnormal microvascular resistance in daily clinical practice. [ABSTRACT FROM AUTHOR]

Coronary endothelial dysfunction and vasospasm are potential causes of ischemia in patients without obstructive coronary stenoses (INOCA). To evaluate the prevalence of endothelial dysfunction and the clinical profile of patients with INOCA in Spain, as well as to identify the predictors and the prognostic impact of endothelial dysfunction in this scenario. A total of 438 consecutive patients with INOCA in whom the acetylcholine test was performed were prospectively enrolled. Patients were followed up at 1 and 2 years. Mean age was 62 ± 11 years with 60% female. Clinical presentation comprised 52.6% angina at rest, 61.2% exertional angina, and 31.7% dyspnea. There were no major complications of the acetylcholine test. Endothelial dysfunction was observed in 198 (45%) of patients, with severe vasoconstriction (defined as over 70% constriction), being observed in 101 (23%). Multivariable regression analysis showed that endothelial dysfunction was predicted by the presence of exertional angina (OR 2.2; CI95%1.01–2.55; p = 0.02), prior coronary disease (OR 2.46; CI95% 1.57–3.89; p < 0.01), and coronary intramyocardial bridging (2.35; CI95% 1.02–5.60; p = 0.04). Patients with endothelial dysfunction presented with worsening angina compared to those without endothelial dysfunction (25.6% vs. 12.8%) and also presented with increased levels of minimal effort angina (40% vs. 26,7%, p = 0.03) more frequently during the follow up than those without endothelial dysfunction. Endothelial dysfunction was also an independent predictor of the occurrence of myocardial infarction or unstable angina at one year (OR 2.85, CI 95% 1.01–9.25; p = 0.03). Endothelial dysfunction is present in almost half of patients with INOCA and is associated with worsening symptoms, as well as with a higher rate of adverse events. [Display omitted] • Almost half of patients with INOCA have coronary endothelial dysfunction. • Exertional angina is a predictor of coronary endothelial dysfunction in INOCA. • Coronary endothelial dysfunction is a predictor of cardiovascular events in patients with INOCA. [ABSTRACT FROM AUTHOR]

• Plasma levels of miR-143 and miR-145 were significantly decreased in ACS patients. • Plasma miR-143 and miR-145 may be important factors in the prevention of acute coronary events. • Both miR-143 and miR-145 can be used to evaluate the degree of coronary artery stenosis. • MiR-143 and miR-145 are expected to be biomarkers of the degree of coronary artery stenosis. Multiple studies have provided evidence that miR-143 and miR-145 play a crucial role in the pathogenesis and progression of atherosclerosis. In the present study, we aim to investigate the expression of plasma miR-143 and miR-145 in patients with acute coronary syndrome (ACS) and their association with the severity of coronary artery stenosis. The study enrolled 279 patients with ACS, including 201 patients with unstable angina (UA) and 78 patients with acute myocardial infarction (AMI), and 65 matched subjects as the control group. The plasma levels of miR-143 and miR-145 were detected by quantitative real-time PCR (qRT-PCR). Gensini score was applied to evaluate the severity of coronary artery stenosis. Plasma levels of miR-143 and miR-145 in patients with ACS were both decreased compared with the control group (p < 0.001). Plasma levels of miR-143 and miR-145 were negatively correlated with Gensini score (miR-143: r = −0.246, p < 0.001; miR-145: r = −0.222, p < 0.001). Logistic regression analysis showed that miR-143 and miR-145 were protective factors for the onset of ACS, UA, or AMI separately. MiR-143 (AUC: 0.786, p < 0.001) and miR-145 (AUC: 0.793, p < 0.001) were able to predict the degree of coronary artery stenosis greater than 50 %. The plasma levels of miR-143 and miR-145 were significantly decreased in ACS patients and were negatively correlated with coronary stenosis. In conclusion, plasma miR-143 and miR-145 levels can be used as noninvasive biomarkers for evaluating coronary artery stenosis. [ABSTRACT FROM AUTHOR]

• As the first study to investigate kinesiophobia in patients with AP of CAD, we have refocused on the effect of "fear of pain" on kinesiophobia in individuals with CAD. • This study provides new insights into the application of kinesiophobia in patients with CAD, which can improve the attention of kinesiophobia in patients with AP of CAD. • We also reviewed the status quo, identified factors related to kinesiophobia and provided guidance for reducing kinesiophobia in patients with AP of CAD. In the field of chronic pain research, kinesiophobia is defined as avoidance behavior due to fear of pain, but this perspective seems to be neglected in the field of coronary artery disease (CAD). To investigate the status quo of angina pectoris (AP) and kinesiophobia and factors associated with kinesiophobia in patients with AP of CAD. This was a cross-sectional study. Participants were recruited by convenience sampling, and patients with AP of CAD in four wards of the Cardiology Department of a hospital were enrolled in this study. Participants completed questionnaires and scales face-to-face with researchers. Most patients with AP of CAD suffered from at least moderate pain episodes (60.2%) of at least 5 minutes per episode (53.8%), but less than 1/3 of patients reached 5 instances of pain per week (29.1%). The total score of kinesiophobia in patients was 40.80±6.65, and the vast majority of patients had moderate to high levels of kinesiophobia (75.7%). The results of multiple linear stepwise regression analysis showed that personal monthly income, New York Heart Function Assessment (NYHA) classification, pain intensity, and pain resilience were independent factors associated with kinesiophobia, and these factors explained 30.2% of the variation in total scores of kinesiophobia. The symptoms of AP were prominent in terms of pain intensity and duration of pain. The level of kinesiophobia was moderate, and this was affected by multiple factors. Health care providers and researchers seldom pay attention to the kinesiophobia of patients with AP of CAD. This study refocused on the effect of "fear of pain" in kinesiophobia in patients with CAD. It opens up new horizons for the application of fear-avoidance models in CAD patients and helps to raise awareness of kinesiophobia in AP patients with CAD and provides guidance for reducing the level of kinesiophobia in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

66-year-old Bengali male with past medical history of hypertension, hyperlipidemia, and diabetes mellitus type 2 was referred to the cardiology clinic for the evaluation and management of angina pectoris. The patient's symptoms were characterized as exertional chest pressure, which worsened with minimal activity (walking for 5 minutes) and relieved with rest (after 10 minutes) and had been ongoing for the past 4-5 months. His existing medications included atenolol, valsartan, and empagliflozin. Based on his clinical history and his risk factors for ischemic heart disease, he had a high pre-test probability for ischemic heart disease. Coronary computed tomographic angiography (CCTA) is an accurate test for the identification of atherosclerotic coronary artery disease (CAD) in patients initially presenting for the evaluation of suspected CAD, especially in those individuals with a high pre-test probability of ischemic heart disease. An initial electrocardiogram demonstrated sinus bradycardia with no ischemic changes. Lipid panel demonstrated total cholesterol of 99 mg/dL, LDL of 35 mg/dL, HDL of 45 mg/dL, and triglycerides of 95 mg/dL. He was referred for CCTA to evaluate the extent and severity of atherosclerotic CAD. CCTA demonstrated moderate calcified coronary plaque with coronary artery calcium Agatston score of 155 and triple vessel disease with severe luminal stenosis as follows: • 50-70% distal left main stenosis comprised of predominantly noncalcified plaque (Image 1). • Diffuse narrowing of the proximal left anterior descending artery comprised of predominantly noncalcified plaque, stenosis quantification could not be done due to absence of a normal reference area (Image 1 & 2). • Subtotal occlusion of the moderately large second diagonal branch secondary to noncalcified plaque (Image 3). • >75% proximal OM1 plaque secondary to noncalcified plaque. • Subtotal occlusion of ostial OM3, followed by 70% stenosis of mid and distal OM3 secondary to noncalcified plaque (Image 4). • Subtotal occlusion of proximal/mid RCA secondary to noncalcified plaque with high-risk features of positive remodeling and low attenuation (Image 5A & 5B). CCTA cardiac functional analysis demonstrated normal ejection fraction, wall motion and chamber size. The patient was started on aspirin and high intensity rosuvastatin. He was referred for coronary angiography which confirmed the CCTA findings of severe triple vessel disease. He was referred for CABG. Post CABG, the patient is feeling well, and his activity level has improved. CCTA is an excellent noninvasive modality for the management of chest pain in patients with high pre-test probability. It is a readily available tool that can identify the severity and extent of CAD, and guide downstream preventative medical management such as aspirin and lipid lowering therapy, as well as invasive management such as coronary catheterization and CABG. When used as an initial gatekeeper modality it can identify those patients who would most benefit most from invasive workup of ischemic heart disease. No [ABSTRACT FROM AUTHOR]

1. Participants will be able to understand the importance in palliative medicine of comprehensive assessments of physical, psychosocial, and spiritual symptoms and needs to most effectively palliate all forms of suffering. 2. Participants will be able to recognize the link between the use of inherently biased, "textbook" descriptions of various symptomatologies and diagnostic anchoring bias, particularly in the care of women and individuals from communities of color. A 64 year-old African American woman with multiple myeloma was admitted after 6 months of progressive failure to thrive characterized by fatigue, dyspnea, constipation, nausea/vomiting, and weight loss. Palliative care consult for symptom management revealed depressed mood in addition to physical suffering. Additional work-up ultimately demonstrated critical multivessel coronary disease, highlighting the dangerous relationship between biased symptomatologies and diagnostic anchoring. Guided by the National Consensus Project guidelines, palliative medicine providers are tasked with completing universal comprehensive assessments to address physical, psychosocial, and spiritual symptoms and needs [1]. In real-world situations, however, providers must often tailor assessments, typically focusing on acute symptoms and the reason for consultation [2], increasing the risk for anchoring bias. Ms. E is a 64 y/o African American woman with multiple myeloma complicated by multiple vertebral fractures on maintenance therapy and a history of coronary artery disease treated with right coronary stent placement 15 years ago. She was admitted from clinic for work-up of a 6-month history of progressive functional decline attributed to fear of ambulation from previous falls. Additionally, she had experienced progressive fatigue, decreased appetite with associated constipation, nausea and vomiting leading to an unintentional 15- pound weight loss in the preceding month. Palliative medicine was consulted primarily for symptom management and found she had severe depressed mood and an inability to discuss her feelings with loved ones. She was also noted to have significant exertional and resting dyspnea associated with her decreased function. She underwent an echocardiogram which was unrevealing. Subsequently, coronary arteriography demonstrated critical multivessel disease. She received two stents and had substantial improvement in all symptoms and functional status at 1 month follow-up. Ms. E presented with several months of unrecognized atypical symptoms of unstable angina leading to profound functional impairment highlighting the fact that "typical symptoms" are most often experienced by Caucasian men. Her underlying malignancy acted as a red herring and her depressed mood was an effect and not the cause of her symptoms, which could only be addressed with proper diagnosis of unstable angina. Addressing her underlying illness was paramount and critical in efforts to effectively palliate her concurrent psychosocial and spiritual suffering. Diversity, Equity, Inclusion, Belonging, Justice / Managing Suffering and Distress [ABSTRACT FROM AUTHOR]

Fractional flow reserve computed tomography (FFRct) allows for non-invasive assessment of hemodynamically significant coronary artery disease (CAD). Real-world data regarding the diagnostic performance of FFRct is scarce. We aim to validate the diagnostic performance of FFRct against invasive coronary angiography (ICA) in patients with stable angina and an abnormal single photon emission computed tomography (SPECT) study. This prospective, single-cohort, real-world study enrolled consecutive adult patients with stable angina and an abnormal SPECT study who were referred for ICA. Prior to ICA, FFRct analysis was performed. Sensitivity and specificity of FFRct were evaluated at the patient and vessel level against ICA. Physician intuition-based diagnosis of hemodynamically significant CAD was also documented prior to ICA. A total of 66 patients were enrolled; 10 were excluded due to protocol deviation or missing studies. FFRct achieved 95% sensitivity and 83% specificity at the patient level, and 78% sensitivity and 88% specificity at the vessel level. FFRct was most accurate in the left circumflex artery (sensitivity 83%, specificity 92%) and the least in the left anterior descending artery (80% sensitivity, 78% specificity). FFRct identified hemodynamically significant CAD more accurately than physician intuition (sensitivity 95% vs 84%; specificity 83% vs 46%). If physicians had been unblinded to FFRct, ICA may have been avoided in up to 53% of patients. We performed a real-world study to validate the diagnostic performance of FFRct against gold-standard invasive imaging. FFRct has high sensitivity and specificity for the diagnosis of hemodynamically significant CAD in intermediate-to-high risk patients. • The gold standard method to assess the functional impact of coronary artery disease (CAD) is invasive coronary angiography (ICA) • Non-invasive fractional flow reserve computed tomography (FFRct) identifies hemodynamically significant CAD • FFRct has a high sensitivity and specificity for predicting functional CAD among patients with abnormal SPECT studies relative to ICA • Addition of FFRct was safe and did not increase risk of MACE or mortality in a real-world setting • FFRct usage could potentially reduce the rate of unnecessary invasive imaging in intermediate-high risk patients with suspected CAD [ABSTRACT FROM AUTHOR]

Ginkgo biloba is a traditional Chinese medicine extracted from the Ginkgophyta and is commonly used in the treatment of cardiovascular diseases in China. Clinical trials have demonstrated the clinical benefits of Ginkgo biloba extract (GBE) preparations for patients with unstable angina pectoris (UAP). The efficacy of different GBE preparations in treating UAP may vary, leading to a lack of guidance for physicians when choosing GBE preparations. How to make choices among different GBE preparations is a topic worthy of investigation. In order to clarify the efficacy differences among different GBE preparations, provide a reference for their optimal use conditions, this study was conducted. This study included literature from eight databases from inception to November 2023. It included UAP patients, with the control group receiving conventional treatment and the treatment group receiving different GBE preparations in addition to conventional treatment. Angina efficacy, electrocardiogram (ECG) improvement, and frequency of angina were chosen as outcomes. This study employed a systematic review and Bayesian network meta-analysis, and the surface under the cumulative ranking (SUCRA) curve was used for estimating the efficacy ranking. A total of 98 studies involving 9513 patients and 9 interventions were included. Compared with conventional treatment, GBE preparations combined with conventional treatment had better efficacy in angina symptoms and ECG improvement. According to the SUCRA ranking, Shuxuening injection was most effective in improving angina symptoms and reducing the frequency of angina. Among oral GBE preparations, Ginkgo tablets had the best performance in improving angina symptoms and ECG manifestations, and reducing the frequency of angina. There was no significant difference in the incidence of adverse events between the treatment group and the control group, and all adverse events were mild and self-limiting. Compared with oral preparations, the incidence of adverse events for injections was higher. GBE preparations may alleviate angina symptoms and myocardial ischemia in the treatment of UAP with favorable safety. Shuxuening injection may be the most effective among all GBE preparations in improving angina symptoms, while Ginkgo tablets may perform best among oral formulations. The optimal use of GBE injection may be for rapidly alleviating angina symptoms and myocardial ischemia in patients with UAP, and oral formulation of GBE may be more suitable for the long-term treatment of patients with milder symptoms. https://www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42022361487 , ID: CRD42022361487. [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary sinus reducer implantation is a percutaneous technique creating a narrowing in the coronary sinus through the implantation of an hourglass-shaped endoprosthesis. It is proposed to reduce symptoms in patients suffering from refractory angina pectoris. This innovative treatment is experiencing a major craze among interventional cardiologists. It is associated with very high procedural success rates. Complications are rare and include coronary sinus dissection or perforation and migration of the device. This review exposes the device implantation technique, the potential anatomical difficulties, the tips and tricks to overcome challenging situations. It also focuses on the prevention and management of potential complications. [ABSTRACT FROM AUTHOR]

Individuals with or at high risk of cardiovascular disease (CVD) often receive long-term treatment with low-density lipoprotein cholesterol (LDL-C) lowering therapies, but whether the effects of LDL-C reduction remain stable over time is uncertain. This study aimed to establish the course of the effects of LDL-C reduction on cardiovascular risk over time. Randomized controlled trials (RCTs) of LDL-C lowering therapies were identified through a search in MEDLINE and EMBASE (1966–January 2023). The primary analyses were restricted to statins, ezetimibe, and proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors, with other therapies included in sensitivity analyses. Random-effects meta-analyses were performed to establish the hazard ratio (HR) for major vascular events (cardiovascular death, myocardial infarction, unstable angina, coronary revascularization, or stroke) per 1 mmol/L LDL-C reduction. Course of the effects over time was assessed using random-effects meta-regression analyses for the association between follow-up duration, age, and the HR for major vascular events per 1 mmol/L LDL-C reduction. Additionally, treatment-by-time interactions were evaluated in an individual participant data meta-analysis of six atorvastatin trials. A total of 60 RCTs were identified (408,959 participants, 51,425 major vascular events). The HR for major vascular events per 1 mmol/L LDL-C reduction was 0.78 (95 % confidence interval [CI] 0.75–0.81). Follow-up duration was not associated with a change in the HR for major vascular events (HR for change per year 0.994; 95 % CI 0.970–1.020; p = 0.66). The HR attenuated with increasing age in primary prevention (HR for change per 5 years 1.097; 95 % CI 1.031–1.168; p = 0.003), but not secondary prevention (HR for change per 5 years 0.987; 95 % CI 0.936–1.040; p = 0.63). Consistent results were found for statin trials only, and all trials combined. In the individual participant data meta-analysis (31,310 participants, 6734 major vascular events), the HR for major vascular events did not significantly change over follow-up time (HR for change per year 0.983; 95 % CI 0.943–1.025; p = 0.42), or age (HR for change per 5 years 1.022; 95 % CI 0.990–1.055; p = 0.18). Based on available RCT data with limited follow-up duration, the relative treatment effects of LDL-C reduction are stable over time in secondary prevention, but may attenuate with higher age in primary prevention. [Display omitted] • Based on all relevant RCTs of lipid-lowering therapies the HR for major vascular events per 1 mmol/L LDL-C reduction is 0.78. • The HR per 1 mmol/L LDL-C reduction is slightly more favourable in primary (0.74) as compared to secondary prevention (0.80). • In secondary prevention, the HR per 1 mmol/L LDL-C reduction is stable over follow-up time and age. • In primary prevention, the HR per 1 mmol/L LDL-C reduction may significantly attenuate with higher age. [ABSTRACT FROM AUTHOR]

• Metabolomic analysis identified significant differences in metabolites such as xylidine, hydroxycaproic acid, butylbenzenesulfonamide, octanetriol, phosphocholine, and medronic acid between myocardial infarction (MI) and unstable angina (UA) patients. • These differential metabolites demonstrated potential for diagnosing and distinguishing between MI and UA. • Pathway analysis linked these metabolites to cardiac hypertrophy, Wnt signaling, and fatty acid oxidation pathways. • The study suggests potential metabolite biomarkers and pathways that are differentially altered in MI compared to UA. • These findings offer new insights for early diagnosis and personalized treatment of acute coronary syndromes, potentially improving the differential diagnosis of MI versus UA. Myocardial infarction (MI) and unstable angina (UA) exhibit overlapping symptoms, yet they require distinct management approaches. Identifying the metabolic differences between MI and UA may facilitate more precise diagnosis and treatment. Metabolomic analysis was conducted on 95 patients, comprising 33 UA patients, 38 MI patients, and 24 normal controls. Serum metabolites were profiled using tandem mass spectrometry coupled with liquid chromatography. Metabolic analysis revealed notable differences in several metabolites, including xylidine, hydroxycaproic acid, butylbenzenesulfonamide, octanetriol, phosphocholine, and medronic acid, between MI and UA. These metabolites displayed promising diagnostic capabilities for distinguishing between MI and UA. Pathway analysis identified connections with cardiac hypertrophy, Wnt signaling, and fatty acid oxidation. Potential metabolite biomarkers and pathways differentially altered in MI compared to UA were identified in this metabolomics study. The results provide new insights into the metabolic signatures of these ischemic heart diseases. With further confirmation, improved early diagnosis and personalized treatment approaches could be facilitated. [ABSTRACT FROM AUTHOR]