Inducible Myocardial Ischemia Research Articles

The prognostic impact of inducible ischemia in severe ischaemic cardiomyopathy: a randomised comparison of medical therapy and revascularisation

Abstract Background The presence of inducible myocardial ischaemia is used to select patients with stable coronary artery disease for revascularisation, based on observational data in patients with preserved left ventricular function. It is unclear if identification of a substrate for ischaemia is prognostic in patients with severe ischaemic left ventricular systolic dysfunction (LVSD). Purpose To determine if the extent of inducible ischaemia by stress perfusion CMR relates to clinical outcomes and/or the response to revascularisation in patients with ischaemic LVSD. Methods Patients enrolled in the REVIVED-BCIS2 randomised trial were eligible for inclusion if they had undergone stress perfusion CMR prior to randomisation (1). Visual assessment of myocardial perfusion and late gadolinium enhancement (LGE) was performed by an independent core laboratory, by consensus of two expert readers who were blinded to trial-group assignment and clinical or outcome data. For this analysis, segmental ischaemia was classified in a binary manner and the overall volume of ischaemia is expressed in relation to total LV mass, defined as [number of ischaemic segments]/16 * 100. The primary composite outcome was all-cause death or aborted sudden death. Secondary outcomes included left ventricular ejection fraction change at 6 and 12-months, cardiovascular death and sustained ventricular arrhythmias. Data are presented as median [IQR] or mean ± standard deviation. Results Of 700 participants enrolled, stress perfusion CMR was acquired in 200, 181 of whom had scans of sufficient quality for core laboratory analysis (91 randomised to percutaneous coronary intervention and 90 to optimal medical therapy; age 69±8 years, 86% male, 40% diabetic, baseline jeopardy score 10 [8-12]). On CMR, LVEF was 28±8%, scar burden was 18% [9-26] and ischaemic burden was 31% [13-56]. There was no association between ischaemic burden and the primary outcome (HR 1.0, p=0.997, CI 0.92-1.09) or any of the secondary outcomes (Figure 1). There was no relationship between ischaemia and randomised treatment group (Figure 2). Conclusion The REVIVED-BCIS2 trial incudes the largest cohort to date of stress perfusion CMR in severe LVSD, randomised to relief of ischaemia or medical therapy alone. In this study, ischaemic burden was not associated with clinical outcomes or the outcome following revascularisation.Figure 1 – HRs for 10% ischaemic burdenFigure 2 - KM plots for primary outcome

Basal and post-stress ceramide-based risk score CERT1 predicts all-cause mortality and nonfatal myocardial infarction in patients with suspected or established coronary artery disease undergoing stress myocardial perfusion scintigraphy

Background and aimWe examined whether a plasma ceramide-based risk score (CERT1 score), a newly proposed tool for cardiovascular risk prediction, is associated with an increased risk of all-cause mortality and nonfatal myocardial infarction in patients with suspected or known coronary artery disease (CAD). Methods and resultsWe studied 167 ambulatory patients who consecutively underwent stress myocardial perfusion scintigraphy (MPS) for clinical reasons in 2017 (at baseline) and then followed for a median of 6 years (inter-quartile range: 4.7–6.6 years). For the calculation of the CERT1 score, both before and after stress MPS, we measured three specific plasma ceramide concentrations [Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1)] and their ratio to Cer(d18:1/24:0) using a targeted liquid chromatography-tandem mass spectrometry assay. The primary outcome of the study was a composite of all-cause mortality or nonfatal myocardial infarction. During a median of 6 years, a total of 50 events occurred (26 all-cause deaths and 24 nonfatal myocardial infarctions). There was a significant association between pre-stress CERT1 risk categories (high vs. low risk) at baseline and the risk of developing the primary composite outcome (unadjusted HR 1.78, 95% CI 1.02–3.14). This risk remained significant after adjustment for age, sex, smoking, diabetes, pre-existing CAD, left ventricular ejection fraction, and stress-induced inducible myocardial ischemia on MPS (adjusted HR 2.28, 95% CI 1.17–4.41, p = 0.015). Almost identical results were observed for post-stress CERT1 risk categories. ConclusionsPre-stress and post-stress CERT1 high-risk categories at baseline were strongly associated with an increased long-term risk of all-cause mortality or nonfatal myocardial infarction in patients with suspected or established CAD.

Role of myocardial strain imaging in diagnosing inducible myocardial ischemia with treadmill contrast-enhanced stress echocardiography

IntroductionThe aim of this study is to analyze the diagnostic value of global longitudinal strain (GLS) in detecting inducible myocardial ischemia in patients with chest pain undergoing treadmill contrast-enhanced stress echocardiography (SE).MethodsWe retrospectively enrolled all patients who underwent invasive coronary angiography after treadmill contrast-enhanced SE. Rest and peak-stress myocardial GLS, segmental LS, and LS of 4-chamber (CH), 2-CH, and 3-CH views were reported. Luminal stenosis of more than 70% or fractional flow reserve (FFR) of < 0.8 was considered significant.ResultsIn total 33 patients were included in the final analysis, among whom sixteen patients (48.4%) had significant coronary artery stenosis. Averaged GLS, 3-CH, and 4-CH LS were significantly lower in patients with critical coronary artery stenosis compared to those without significant stenosis (-17.1 ± 7.1 vs. -24.2 ± 7.2, p = 0.041), (-18.2 ± 8.9 vs. -24.6 ± 8.2, p = 0.045) and (-14.8 ± 6.2 vs. -22.8 ± 7.8, p = 0.009), respectively. Receiver operating characteristic (ROC) analysis of ischemic and non-ischemic segments demonstrated that a cut-off value of -20% of stress LS had 71% sensitivity and 60% specificity for ruling out inducible myocardial ischemia (Area under the curve was AUC = 0.72, P < 0.0001).ConclusionMyocardial LS measured with treadmill contrast-enhanced stress echocardiography demonstrates potential value in identifying patients with inducible myocardial ischemia.

WELLENS SYNDROME OR PNEUMONIA?

Abstract Background Wellens syndrome, also known as "left anterior descending coronary syndrome," is characterized by the appearance of T–wave changes recorded on the ECG and it is an ECG manifestation of critical proximal left anterior descending artery stenosis. Case Report A 65–year–old man from Bangladesh with a history of chronic ischemic heart disease and trivessel coronary artery disease following surgical revascularization (CABG 2007). Recent admission for NSTEMI (June 2022) with unchanged coronary angiography compared to the previous one. Comorbidities include peripheral arterial disease, type II diabetes with organ damage, and COPD with recent exacerbations. Last myocardial scintigraphy (2021) was positive for inducible myocardial ischemia in the posterolateral region. Admission due to fever, productive cough, and severe chest pain. Initial instrumental assessments revealed ST–segment alterations in inferior leads and V1–V2 with negative/isodiphasic T–waves, not present in previous ECG tracings. A slight troponin elevation with ischemic curve (101 → 303 → 277 → 155 pg/dl, normal range &amp;lt; 50 pg/dl) led to the diagnosis of NSTEMI. Echocardiogram showed concentric remodeling of the left ventricle with normal global systolic function and hypokinesia of the mid–basal inferior wall (noted). Additionally, chest CT revealed pulmonary consolidations in the right middle lobe and upper left lobe, prompting antibiotic therapy and bronchodilator inhalation. Arterial blood gas analysis: pH 7.45, pO2 83, Lactate 0.8, HCO3– 24, P/F 360. Coronary angiography showed an unchanged picture compared to the previous one (patent AMIS and AMID, good run–off in native branches, no distal stenosis at the anastomosis). Clinical symptoms, inflammatory indices, and myocardial damage markers clinically improved during hospitalization. Discharged after optimization of anti–ischemic therapy with DAPT and diagnosis of NSTEMI. However, ECG abnormalities persisted at discharge (negative T–waves in DI–aVL–V1–V2). Post–discharge cardiac MRI was requested. Conclusions Diagnostic hypotheses include, primarily, a possible type II myocardial infarction due to an ongoing pneumonia (although hypoxia/hypovolemia/hypotension sufficient to cause MI was never documented during hospitalization), MINOCA, or microcirculatory disease (functional tests such as iFR/FFR, ACh, IMR were not performed during coronary angiography), or a possible myocarditic outcome (pending MRI).

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease

BackgroundThe endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD).AimTo investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD.MethodsA total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient.ResultsIn the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD.ConclusionIn this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.

Seeing is believing: pathway strategies for a personalised non-invasive diagnosis of coronary artery disease.

Coronary artery disease (CAD) diagnosis requires a precise assessment of patient profile and disease extension. While non-invasive imaging modalities offer an in-depth evaluation of CAD through differential approaches, this is based primarily on detecting coronary plaques or inducible myocardial ischaemia, thus eachoffering only a partial outlook of this condition. The improvement in appropriately identifying CAD patients at risk of developing major adverse cardiovascular events and guiding treatment outcomes will require developing a personalised diagnostic strategy for a value-based application of current technologies.

Myocardial perfusion in cardiac amyloidosis.

Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test.

Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2 , O2 pulse trajectory, and exercise ECG test. Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 to -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001). Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

Echocardiographic functional determinants of survival in heart failure with abnormal ejection fraction.

Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion and EF. In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66 ± 12 years, 1,035 men), with EF <50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability <10% for CFV measurement. Baseline CFV (abnormal value >31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. CFVR (abnormal value ≤2.0) was assessed with exercise (n = 99), dobutamine (n = 100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress > rest (cut-off Δ ≥ 0.12). LV contractile reserve (CR) was identified with WMSI stress < rest (cutoff Δ ≥ 0.25). Test response ranged from score 0 (EF > 30%, CFV ≥ 32 cm/s, CFVR > 2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only endpoint. Results. During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, p < 0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, p < 0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, p < 0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, p < 0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, p = 0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n = 61) and highest (31.9%) in patients with a score of 5 (n = 15, p < 0.001). High resting CFV is associated with worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.

Exercise-induced pulmonary congestion is a promising marker to diagnose early stage heart failure in patients referred to rule out myocardial ischemia

Abstract Backgrounds Pulmonary congestion assessed by B-lines using lung ultrasound (LUS) is a hallmark of heart failure (HF). Latent HF at rest can be unmasked during exercise but the diagnosis remains challenging. Exercise-induced B-lines could help diagnose HF with preserved left ventricular ejection fraction (LVEF) at an early stage. The patients in whom coronary artery disease is suspected are also at risk of HF. Objectives To assess exercise-induced pulmonary congestion in patients referred to rule out myocardial ischemia. Methods Data of stress echocardiography combined with LUS at rest and immediately after exercise in patients with LVEF≥50% referred for investigation of inducible myocardial ischemia in a tertiary center of cardiology, during a 3-years period of time, were retrospectively analyzed. Patients with induced myocardial ischemia, hypertrophic cardiomyopathy or moderate to severe valvular disease were excluded. B-lines were assessed by scanning 2 chest sites. Exercise-induced pulmonary congestion was defined as an increase of B-lines ≥ 2 between baseline and exercise. Results A total of 1114 patients were included. Mean age was 63±11 years, 54% of patients had hypertension and 27% diabetes. Exercise-induced pulmonary congestion was identified in 131 (12%) patients. Age, left atrial volume index (LAVi), resting and 20W septal E/e’&amp;gt;15 and peak tricuspid regurgitation velocity (TRV) were associated with exercise-induced B-lines. In a multivariate logistic regression analysis, LAVi (Odds ratio (OR) = 1.03; 95%confidence interval (CI): 1.01–1.06; p = 0.003) and peak TRV (OR = 3.8; 95%CI: 1.4–10.1; p = 0.009) were independent predictors of exercise-induced pulmonary congestion. Conclusion Exercise-induced pulmonary congestion could be diagnosed in patients with preserved LVEF referred to rule out inducible myocardial ischemia. Exercise B-lines are linked with left ventricular diastolic dysfunction indices.

Independent prognostic value of ejection fraction, resting coronary flow, coronary flow reserve, myocardial viability, and inducible ischemia in heart failure with a reduced ejection fraction

Abstract Background and Aims Patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF) have a heterogeneous prognosis, and assessment of coronary physiology with coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) may complement established predictors based on wall motion. Methods and results In a prospective multicenter study design, we enrolled 1,408 HF patients (age 66±12 years, 1,035 men), with EF &amp;lt;50%, 743 (53%) with coronary artery disease, and 665 (47%) with normal coronary arteries. Recruitment (years 2004-2022) involved 8 accredited laboratories, with inter-observer variability &amp;lt;10% for CFV measurement. Baseline CFV (abnormal value &amp;gt;31 cm/s) was obtained by pulsed-wave Doppler in mid-distal LAD. Coronary flow velocity reserve (CFVR, abnormal value ≤2.0) was assessed with exercise (n=99), dobutamine (n=100), and vasodilator stress (dipyridamole in 1,149, adenosine in 60). Inducible myocardial ischemia was identified with wall motion score index (WMSI) stress&amp;gt; rest (cut-off ∆≥0.12). LV contractile reserve (CR) was identified with WMSI stress&amp;lt; rest (cutoff ∆≥0.25). Test response ranged from score 0 (EF&amp;gt;30%, CFV ≤31 cm/s, CFVR &amp;gt;2.0, LVCR present, ischemia absent) to score 5 (all steps abnormal). All-cause death was the only end-point. Results During a median follow-up of 990 days, 253 patients died. Independent predictors of death were EF (HR: 0.956, 95% CI: 0.943-0.968, p&amp;lt;0.0001), CFV (HR: 2.407, 95% CI: 1.871-3.096, p&amp;lt;0.001), CFVR (HR: 3.908, 95% CI: 2.903-5.260, p&amp;lt;0.001), stress-induced ischemia (HR: 2.223, 95% CI: 1.642-3.009, p&amp;lt;0.001), and LVCR (HR: 0.524, 95% CI: 0.324-.647, p=0.008). The annual mortality rate was lowest (1.2%) in patients with a score of 0 (n=61) and highest (31.9%) in patients with a score of 5 (n=15, p&amp;lt;0.001). Conclusion High resting CFV predicts worse survival in ischemic and nonischemic HF with reduced EF. The value is independent and additive to resting EF, CFVR, LVCR, and inducible ischemia.

Men with non-obstructive coronary disease have higher risk of exercise-induced myocardial ischemia detected by cardiopulmonary exercise test

Abstract Background Non-obstructive coronary artery disease (NOCAD) had similar morbidity and mortality as patients with obstructive coronary artery disease but less understood. Limited studies analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD. Methods A total of 289 NOCAD patients (mean age 60, 56% women) who had ischemic symptoms and ⫹ 50% coronaries stenoses confirmed by coronary angiography performed the symptom-limited CPET. We used the predicted % peak VO2, O2 pulse trajectory, and exercise ECG test to assess inducible myocardial ischemia. Results Compared with women, men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%) and downward pattern of O2 pulse trajectory (2% vs. 0%) (P &amp;lt; 0.0001). Instead, women with NOCAD had higher prevalence of shallow pattern of O2 pulse trajectory (21% vs. 6%, P &amp;lt; 0.0001). Men with NOCAD had higher proportions of increased risk of exercise-induced myocardial ischemia (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, P &amp;lt; 0.0001). After adjustment, men with NOCAD demonstrated significantly lower predicted % peak VO2 (β -27.4, 95% CI -30.74 – -24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 – 9.19) and myocardial ischemia risk detected by CPET (OR 3.14, 95% CI 1.78 – 5.54) (P &amp;lt; 0.0001). Conclusion Men with NOCAD had higher risk of exercise-induced myocardial ischemia detected by CPET that should be given rigorous management and follow-up to prevent cardiovascular events.

Abstract 13988: Post Stress Test High-Sensitivity Cardiac Troponin I in the Evaluation of Patients With Acute Chest Pain for Enhanced Ischemic Risk Assessment: A Pilot Study

Introduction: High-sensitivity cardiac troponin I (hs-cTnI) assays provide comparable diagnostic information that allow for better detection of myocardial injury. However, hs-cTnI release after cardiac stress testing and its potential utility for identifying inducible myocardial ischemia and risk-stratification are unclear. Aim: This pilot study examined integrating hs-cTnI biomarker testing into cardiac imaging stress testing to improve detection of inducible ischemia and aid in risk-stratification in patients with chest pain being evaluated for acute coronary syndrome (ACS). Methods: We prospectively enrolled 200 consecutive adult patients referred by the Emergency Room for cardiac stress testing for evaluation of possible ACS. A venous blood sample was collected between 0.5 and 2 hours post stress testing; cTnI concentrations were measured in-house by high sensitivity methods. Changes from pre-stress test hs-cTnI concentrations were calculated and association with outcome was explored using a logistic regression model. Results: Patient median age was 62 years, IQR 54-70; 49% were women. ACS known risk factors included hypertension 81.5%, cigarette smoking 49.5% and diabetes 33.5%. Median BMI was 31.63 kg/m 2 , IQR 27.24-35.84. Pre-stress test hs-cTnI median levels were 6 ng/L, IQR 5-9, for women (URL &lt;52 ng/L) and 8 ng/L, IQR 6-12, for men (URL &lt;77 ng/L). A total of 121 patients (60.5%) underwent nuclear stress tests, and 79 (39.5%) received echocardiographic stress tests. Of the 191 samples analyzed, 36% revealed increased hs-cTnI levels from pre-stress test values: 33% in nuclear stress tests (median increase 2 ng/L, IQR 1-5), 41% in echocardiographic stress tests (median increase 2 ng/L, IQR 1-5). In the 155 patients with 6 months of follow-up, changes in post-stress test hs-cTnI levels were not significantly correlated to stress test results, percutaneous coronary interventions or death (p=.85). Conclusion: This study provides insight into the potential of hs-cTnI to aid in identifying inducible myocardial ischemia in a real-world, high-throughput setting. Although a subset of patients exhibited modest increases in hs-cTnI post stress testing, overall, these did not appear to be correlated with inducible myocardial ischemia.

Decline in typical angina among patients referred for cardiac stress testing

ObjectiveTo evaluate temporal trends in the prevalence of typical angina and its clinical correlates among patients referred for stress/rest SPECT myocardial perfusion imaging (MPI). Patients and methodsWe evaluated the prevalence of chest pain symptoms and their relationship to inducible myocardial ischemia among 61,717 patients undergoing stress/rest SPECT-MPI between January 2, 1991 and December 31, 2017. We also assessed the relationship between chest pain symptom and angiographic findings among 6,579 patients undergoing coronary CT angiography between 2011 and 2017. ResultsThe prevalence of typical angina among SPECT-MPI patients declined from 16.2% between 1991 and 1997 to 3.1% between 2011 and 2017, while the prevalence of dyspnea without any chest pain increased from 5.9 to 14.5% over the same period. The frequency of inducible myocardial ischemia declined over time within all symptom groups, but its frequency among current patients (2011–2017) with typical angina was approximately three-fold higher versus other symptom groups (28.4% versus 8.6%, p < 0.001). Overall, patients with typical angina had a higher prevalence of obstructive CAD on CCTA than those with other clinical symptoms, but 33.3% of typical angina patients had no coronary stenoses, 31.1% had 1–49% stenoses, and 35.4% had ≥ 50% stenoses. ConclusionsThe prevalence of typical angina has declined to a very low level among contemporary patients referred for noninvasive cardiac tests. The angiographic findings among current typical angina patients are now quite heterogeneous, with one-third of such patients having normal coronary angiograms. However, typical angina remains associated with a substantially higher frequency of inducible myocardial ischemia compared to patients with other cardiac symptoms.

The Role of Non-Invasive Multimodality Imaging in Chronic Coronary Syndrome: Anatomical and Functional Pathways.

Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, with a high socioeconomic impact. Currently, various guidelines and recommendations have been published about chronic coronary syndromes (CCS). According to the recent European Society of Cardiology guidelines on chronic coronary syndrome, a multimodal imaging approach is strongly recommended in the evaluation of patients with suspected CAD. Today, in the current practice, non-invasive imaging methods can assess coronary anatomy through coronary computed tomography angiography (CCTA) and/or inducible myocardial ischemia through functional stress testing (stress echocardiography, cardiac magnetic resonance imaging, single photon emission computed tomography-SPECT, or positron emission tomography-PET). However, recent trials (ISCHEMIA and REVIVED) have cast doubt on the previous conception of the management of patients with CCS, and nowadays it is essential to understand the limitations and strengths of each imaging method and, specifically, when to choose a functional approach focused on the ischemia versus a coronary anatomy-based one. Finally, the concept of a pathophysiology-driven treatment of these patients emerged as an important goal of multimodal imaging, integrating 'anatomical' and 'functional' information. The present review aims to provide an overview of non-invasive imaging modalities for the comprehensive management of CCS patients.

Diagnostic and Prognostic Value of Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease

The clinical utility of stress cardiovascular magnetic resonance imaging (CMR) in stable chest pain is still debated, and the low-risk period for adverse cardiovascular (CV) events after a negative test result is unknown. To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain. PubMed and Embase databases, the Cochrane Database of Systematic Reviews, PROSPERO, and the ClinicalTrials.gov registry were searched for potentially relevant articles from January 1, 2000, through December 31, 2021. Selected studies evaluated CMR and reported estimates of diagnostic accuracy and/or raw data of adverse CV events for participants with either positive or negative stress CMR results. Prespecified combinations of keywords related to the diagnostic accuracy and prognostic value of stress CMR were used. A total of 3144 records were evaluated for title and abstract; of those, 235 articles were included in the full-text assessment of eligibility. After exclusions, 64 studies (74 470 total patients) published from October 29, 2002, through October 19, 2021, were included. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Diagnostic odds ratios (DORs), sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), odds ratio (OR), and annualized event rate (AER) for all-cause death, CV death, and major adverse cardiovascular events (MACEs) defined as the composite of myocardial infarction and CV death. A total of 33 diagnostic studies pooling 7814 individuals and 31 prognostic studies pooling 67 080 individuals (mean [SD] follow-up, 3.5 [2.1] years; range, 0.9-8.8 years; 381 357 person-years) were identified. Stress CMR yielded a DOR of 26.4 (95% CI, 10.6-65.9), a sensitivity of 81% (95% CI, 68%-89%), a specificity of 86% (95% CI, 75%-93%), and an AUROC of 0.84 (95% CI, 0.77-0.89) for the detection of functionally obstructive coronary artery disease. In the subgroup analysis, stress CMR yielded higher diagnostic accuracy in the setting of suspected coronary artery disease (DOR, 53.4; 95% CI, 27.7-103.0) or when using 3-T imaging (DOR, 33.2; 95% CI, 19.9-55.4). The presence of stress-inducible ischemia was associated with higher all-cause mortality (OR, 1.97; 95% CI, 1.69-2.31), CV mortality (OR, 6.40; 95% CI, 4.48-9.14), and MACEs (OR, 5.33; 95% CI, 4.04-7.04). The presence of late gadolinium enhancement (LGE) was associated with higher all-cause mortality (OR, 2.22; 95% CI, 1.99-2.47), CV mortality (OR, 6.03; 95% CI, 2.76-13.13), and increased risk of MACEs (OR, 5.42; 95% CI, 3.42-8.60). After a negative test result, pooled AERs for CV death were less than 1.0%. In this study, stress CMR yielded high diagnostic accuracy and delivered robust prognostication, particularly when 3-T scanners were used. While inducible myocardial ischemia and LGE were associated with higher mortality and risk of MACEs, normal stress CMR results were associated with a lower risk of MACEs for at least 3.5 years.

PATIENTS WITH VERY HIGH RISK OF CARDIOVASCULAR ADVERSE EVENTS DURING CARFILZOMIB THERAPY: PREVENTION AND MANAGEMENT OF EVENTS IN A SINGLE CENTER EXPERIENCE

Objective: Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients, but has shown cardiovascular toxicity. The cardiovascular adverse events (CVAEs) risk stratification now seems well established, while little is known about the course and management of patients with high risk or CVAEs during therapy. So, we aimed to describe our specialistic experience in decision-making to support health professionals in selecting the best management strategies to prevent and treat CVAEs. Design and method: From January 2015 to September 2022, 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We proposed a novel approach with inducible ischemia imaging tests for patients at high baseline CV risk to rule out clinical conditions that could contraindicate the starting of CFZ. Results: After baseline evaluation, 16 (8.2%) patients resulted at high risk of CVAEs: 13 (6.7%) patients performed inducible myocardial ischemia imaging test and 3 (1.5%) could not receive CFZ for CV contraindications. 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial hyperten-sion-related events and 37 (20.8%) major CVAEs (Fig. 1); 19 (10.7%) patients had to suspend or remodulate CFZ. Conclusions: Together with baseline risk stratification also subsequent cardiovascular clinical and diagnostic follow-up appeared critical to identify clinical conditions that could contraindicate the anti-cancer therapy.

P54 RIGHT SINGLE CORONARY ARTERY AS AN INCIDENTAL FINDING IN ACUTE PERICARDIAL DISEASE

Abstract An 44–year–old woman was referred to our hospital for chest pain. She had no known cardiovascular risk factors but had a history of previous acute pericarditis following pregnancy. At admission, she still had chest pain improved by leaning forward. Cardiovascular examination and her electrocardiogram showed nothing pathological. On laboratory tests, there were mild elevation of troponin T and normal C–reactive protein. A transthoracic echocardiogram revealed only a minimal pericardial effusion close to the right heart chambers. A chest X–ray was generally normal. She was admitted to the coronary care unit with a provisional diagnosis of myopericarditis. Three days later, due to the persistence of symptoms despite the appropriate pharmacological therapy, it was decided to perform coronary angiography. During the procedure, selective cannulation of the left coronary artery was not possible, and a non–selective injection disclosed no coronary artery arising from the left coronary sinus. On selective injection of the right coronary sinus, a single ostium was visualized. The right coronary artery (RCA) was a great vessel, with no stenosis. A left anterior descending artery (LAD) and left circumflex artery (LCx) were perfused from RCA collateral vessels, both without lesions. Coronary computed tomography angiography confirmed a single coronary artery with its ostium in the right sinus of Valsalva and agenesis of the left main artery (LCA). A physical stress echo ruled out inducible myocardial ischemia. Coronary artery anomalies are rare congenital disorders that are usually diagnosed incidentally. Single coronary artery (SCA) has been known since 1903. It is an anomalous condition in which the SCA originates from a single aortic orifice, either the left or the right aortic ostium, and gives rise to the entire coronary circulation. Isolated congenital SCA is a very rare condition, occurring in 0.024–0.098% of the general population. Right SCA with congenital absence of the LCA is the least common type of SCA, and is extremely rare with a reported incidence of 0.0008%. SCA has been reported in association with atherosclerotic disease, coronary artery fistulas, mitral valve prolapse, bicuspid aortic valves, tetralogy of Fallot, transposition of the great arteries, hypertrophic cardiomyopathy and Takotsubo syndrome. We report this extremely rare case because the concomitant association with pericardial diseases has never previously been reported.

Exercise-induced pulmonary congestion assessed by lung ultra sound in patients with preserved left ventricular ejection fraction referred for exercise echocardiography to rule out myocardial ischemia

Lung ultrasound (LUS) can detect pulmonary congestion assessed by B-lines in heart failure patients undergoing stress test. Exercise B-lines could help diagnose heart failure with preserved left ventricular ejection fraction (LVEF) at an early stage. This study aimed to assess exercise-induced pulmonary congestion in patients with preserved LVEF referred for exercise echocardiography to rule out myocardial ischemia. Data of stress echocardiography combined with LUS at rest and immediately after exercise in patients with LVEF ≥ 50% referred for investigation of inducible myocardial ischemia in a tertiary center of cardiology were retrospectively analyzed. B-lines were assessed by scanning 2 chest sites. Exercise-induced pulmonary congestion was defined as an increase of B-lines ≥ 2 between baseline and exercise. A total of 1114 patients were included. Mean age was 63 years, 54% of patients had hypertension and 27% had diabetes. Exercise-induced pulmonary congestion was identified in 131 (12%) patients. Age, left atrial volume index (LAVi), resting and 20 W septal E/e’ > 15 and peak tricuspid regurgitation velocity (TRV) were associated with increased exercise-induced B-lines. At multivariable analysis, LAVi (OR = 1.03; 95% confidence interval (CI): 1.01–1.06; P = 0.003) and peak TRV (OR = 3.8; 95%CI: 1.4–10.1; P = 0.009) were independent predictors of exercise-induced pulmonary congestion. Exercise-induced pulmonary congestion could be diagnosed in patients with preserved LVEF referred to rule out inducible myocardial ischemia. Exercise B-lines are linked with left ventricular diastolic dysfunction indices.

SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

BackgroundSodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up.MethodsIn a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis.ResultsAt 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149–2.176]), macrophage grade (1.188, [CI 95%: 1.073–1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180–0.651]) were independent predictors of MACEs at 1 year of follow-up.ConclusionsSGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids’ deposit, and FCT in Mv-NOCS patients with T2DM.