Ischemia And No Obstructive Coronary Artery Disease Research Articles

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography

ObjectiveTo compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). MethodsThe WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. ResultsAn initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. ConclusionsAmong this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Noninvasive evaluation of dynamic microvascular dysfunction in ischemia and no obstructive coronary artery disease patients with suspected vasospasm.

In patients with ischemia and no obstructive coronary artery disease (INOCA), a dynamic coronary microvascular dysfunction (CMD) is frequent but difficult to capture by noninvasive means.The aim of our study was to assess dynamic CMD in INOCA patients with stress echocardiography after vasoconstrictive and vasodilator stimuli. In this prospective single-center study, we have enrolled 40 INOCA patients (age 56.3 ± 13 years, 32 women). All participants underwent stress echocardiography with hyperventilation (HYP), followed by supine bicycle exercise (HYP+EXE) and adenosine (ADO). Stress echocardiography included an assessment of regional wall motion abnormality (RWMA) and coronary flow velocity (CFV) in the distal left anterior descending (LAD) coronary artery. HYP induced a 30% increase in rate pressure product (rest = 10 244 ± 2353 vs. HYP = 13 214 ± 3266 mmHg x bpm, P < 0.001) accompanied by a paradoxical reduction in CFV (HYP< rest) in 21 patients (52%). HYP alone was less effective than HYP+EXE in inducing anginal pain (6/40, 15% vs. 10/40, 25%, P = 0.046), ST segment changes (6/40, 15% vs. 24/40, 60%, P < 0.001), and RWMA (6/40, 15% vs. 13/40, 32.5%, P = 0.008). ADO-induced vasodilation was preserved (≥2.0) in all patients. In patients with INOCA, a coronary vasoconstriction after HYP is common, in absence of structural CMD detectable with ADO. HYP+EXE test represents a more powerful ischemia inducer than HYP alone. Stress echocardiography with LAD-CFV may allow the noninvasive assessment of dynamic and structural coronary microcirculation during stress.

Long-term outcomes of patients with ischemia and no obstructive coronary artery disease (INOCA) - a systematic review and meta-analysis

Abstract Background Myocardial ischemia with no obstructive coronary artery disease (INOCA) is an increasingly recognized syndrome that encompasses coronary vasomotor disorders such as coronary microvascular dysfunction (CMD) and coronary vasospasm. However, the prognosis of patients with INOCA is not well defined. Purpose To perform a systematic review and meta-analysis of previous studies evaluating the long-term prognosis of patients with INOCA stratified by the underlying vasomotor disorder. Methods We searched Medline, Embase, Web of Science, and Cochrane databases combining terms for INOCA and outcomes to identify observational studies evaluating the prognosis of patients with INOCA published between 1984 and 2021. The primary outcomes were composite of all-cause death and MI, and major adverse cardiovascular events (MACE) at annual intervals for up to 5-year follow-up. Meta-analytic averages with 95% confidence intervals (CI) of the incidence of primary outcomes for INOCA, each INOCA endotype, and by method used to determine the diagnosis were calculated using the random effect models. Results We identified a total of 52 studies (19765 patients) meeting eligibility criteria. Of those, 22 included patients with vasospastic angina and 34 with microvascular angina. The rate of all-cause death and MI in the vasospastic angina group was 0.7 (95% CI 0.4-1.0)/100 patient-years [Figure 1] and the rate of MACE was 1.1 (95% CI 0.6-1.9)/100 patient-years [Figure 2]. For patients with microvascular angina the rate of all cause death and MI was 1.2 (95% CI 0.7-1.7)/100 patient-years [Figure 1] and the rate of MACE was 2.8 (95% CI 1.8-4.0)/100 patient-years [Figure 2]. Patients with evidence of microvascular dysfunction by non-invasive (CFR) or invasive (CFR, IMR, TIMI frame count) criteria had 2.7 times higher all-cause death and MI rates than patients whose diagnosis was established solely based on an abnormal exercise or imaging stress test (2.6 (95% CI, 0.8-5.1) vs. 0.7(95% CI, 0.4-1.2)/100 patient-years, p=0.034). Conclusions Overall, patients with INOCA have a low rate of MACE events or death, although there is heterogeneity based on the underlying phenotype. Patients with vasospastic angina have a relatively benign long-term prognosis, whereas patients with microvascular angina have a significantly higher rate of MACE at long-term follow-up. Among patients with microvascular angina, those with objective evidence of abnormal microvascular function (such as reduced CFR) had 2.7 times higher rates of all-cause death and MI.Incidence of all cause death and MIIncidence of MACE

Non-hyperaemic coronary flow velocity acceleration indices correlate with hyperaemic microvascular resistance in patients with INOCA

Abstract Background Coronary microvascular dysfunction (CMD) is associated with an overall worse prognosis. While the diagnosis and endo-typing of CMD currently rely on hyperaemic physiological indices, the search for accurate non-hyperaemic techniques continues. Flow velocity acceleration pattern is mechanistically associated with changes in shear stress, endothelial function, arterial stiffness and pressure in pulsatile flow systems (1-3). Purpose We aim to interrogate whether resting flow velocity acceleration indices correlate with hyperaemic microvascular resistance (HMR) in patients with Ischemia and no obstructive coronary artery disease (INOCA). Methods In 21 Patients with INOCA (all of whom had presented with typical angina pectoris, had no significant epicardial stenoses but positive myocardial perfusion scan test for ischemia) invasive physiological assessment was performed by means of intracoronary Doppler. Hyperaemia was induced with intracoronary adenosine administration. Coronary flow reserve (CFR) and HMR were calculated per their definitions. Flow velocity acceleration indices were derived from the first derivative of the averaged resting flow velocity waveforms with respect to time. We have defined 6 wave peaks of interest in all patients (peak diastolic acceleration (initial prominent peak with ventricular relaxation, referred as A), early diastolic deceleration (B), early re-acceleration wave (C), peak presystolic deceleration (seen just before initial systolic acceleration peak, J), initial systolic acceleration peak (X) and pre-diastolic deceleration nadir (Z)) and calculated the ratios between them as well as adjusted them with respect to resting mean flow velocity (Figure 1). Results The mean age was 59 ± 8 years and the majority of the study group was female (%81). Cardiovascular risk factors were common amongst the study group.All patients had CFR &amp;lt; 2.5. Mean CFR and HMR were 2.05 ± 0.32 and 2.20 ± 0.60 mmHg.cm.sec-1 respectively. Raw C peak magnitude was significantly correlated with APVh (rho:-0.457 p:0.037) and HMR (rho:0.612 p:0.004). Adjusting the C magnitudes with APVb at patient level yielded better correlations (APVh rho:-0.496 p:0.022 ; HMR:0.642 p:0.002). The ratio between diastolic reacceleration peak (C) and presystolic peak deceleration (J), C/J , adjusted with the APVb ((C/J)/APVb) showed the most pronounced correlation with HMR (rho: 0.758 p &amp;lt; 0.001) (unadjusted C/J – HMR rho: 0.718 p&amp;lt;0.001)(Figure 2). Conclusion(s) Acceleration characteristics of resting coronary flow velocity correlate with hyperaemic microvascular resistance indicating structurally impaired coronary microcirculation, hence their utilisation may aid developing non-hyperaemic physiological markers for coronary microvascular dysfunction in patients with INOCA.Derived Acceleration WaveformsCorrelations between HMR and C/J Ratio

Abstract 15736: Coronary Angiography Alone Compared With Invasive Coronary Function Testing in Women With Ischemia and No Obstructive Coronary Artery Disease

Introduction: Ischemic heart disease is a leading cause of morbidity and mortality in women. Women frequently suffer from ischemia and no obstructive coronary artery disease (INOCA) which includes phenotypes of coronary microvascular dysfunction (CMD) or coronary vasospasm (VA). Between 30-60% of women referred for invasive angiography have non obstructive coronary arteries, leaving many patients without a definitive diagnosis. Objective: We sought to determine the real-world diagnostic yield of invasive physiological testing in women with INOCA, and to describe downstream care regarding modifications to medical therapy based on the eventual diagnosis. Methods: We included 198 women who underwent either coronary angiography (CA, N=99) alone or coronary function testing (CFT, N=99) comprised of acetylcholine provocation and assessment of coronary flow reserve and the index of microcirculatory resistance. We performed a descriptive retrospective analysis of demographics, pre-procedure diagnostic testing and used logistic regression to compare the findings of angiography, post-procedure diagnosis, and changes to cardiac medications across cohorts. Results: The mean age was 62 ± 10 (CA alone) compared with 57 ± 10 years (CFT). Patients were mostly white (72% CA vs 79% CFT). An angiography-based diagnosis of normal coronary arteries was found in 21% CA alone (N=21) vs 48% in CFT (N=48) and non-obstructive CAD in 79% CA alone (N=78) vs 51% CFT (N=50), p&lt;0.001. Of the women who underwent CFT, 76% (N=75) were diagnosed with a vasomotor disorder stratified by endotype of CMD 34% (n=34), VA 22% (n=22), mixed CMD/VA 10% (N=10) or endothelial dysfunction 20% (N=20). Medications were changed after angiography in 41% in the CA alone group compared to 67% in the CFT group, p&lt;0.001; while medication changes at 30 days occurred in 22% CA alone vs 45% in the CFT group, p&lt;0.001. Conclusions: Our findings demonstrate that women presenting with suspected ischemic heart disease undergoing coronary angiography often received a diagnosis of non-obstructive coronary artery disease; whereas those undergoing CFT were diagnosed with coronary vasomotor disorders. In our institution, medication changes occurred more frequently after a CFT-confirmed diagnosis.

Quantitative Flow Ratio-Derived Index of Microcirculatory Resistance as a Novel Tool to Identify Microcirculatory Function in Patients with Ischemia and No Obstructive Coronary Artery Disease

Background: Coronary microvascular disease (CMVD) is associated with adverse cardiovascular outcomes. However, there is no reliable and noninvasive quantitative diagnostic method available for CMVD. The use of a pressure wire to measure the index of microcirculatory resistance (IMR) is possible, but it has inevitable practical restrictions. We hypothesized that computation of the quantitative flow ratio could be used to predict CMVD with symptoms of ischemia and no obstructive coronary artery disease (INOCA). Methods: We retrospectively assessed the diagnostic efficiency of the quantitative flow ratio-derived index of microcirculatory resistance (QMR) in 103 vessels from 66 patients and compared it with invasive IMR using the thermodilution technique. Results: Patients were divided into the CMVD group (41/66, 62.1%) and non-CMVD group (25/66, 37.9%). Pressure wire IMR measurements were made in 103 coronary vessels, including 44 left descending arteries, 18 left circumflex arteries, and 41 right coronary arteries. ROC curve analysis showed a good diagnostic performance of QMR for all arteries (area under the curve = 0.820, 95% confidence interval 0.736–0.904, p < 0.001) in predicting microcirculatory function. The optimal cut-off for QMR to predict microcirculatory function was 266 (sensitivity: 82.9%, specificity: 72.6%, and diagnostic accuracy: 76.7%). Conclusion: QMR is a promising tool for the assessment of coronary microcirculation. The assessment of the IMR without the use of a pressure wire may enable more rapid, convenient, and cost-effective assessment of coronary microvascular function.

Global Longitudinal Strain as Predictor of Inducible Ischemia in No Obstructive Coronary Artery Disease in the CIAO-ISCHEMIA Study

Global longitudinal strain (GLS) is a sensitive marker for identifying subclinical myocardial dysfunction in obstructive coronary artery disease (CAD). Little is known about the relationship between GLS and ischemia in patients with myocardial ischemia and no obstructive CAD (INOCA). To investigate the relationship between resting GLS and ischemia on stress echocardiography (SE) in patients with INOCA. Left ventricular GLS was calculated offline on resting SE images at enrollment (n=144) and 1-year follow-up (n=120) in the CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial screen failures with no obstructive CAD on computed tomography [CT] angiography) study, which enrolled participants with moderate or severe ischemia by local SE interpretation (≥3 segments with new or worsening wall motion abnormality and no obstructive (<50% stenosis) on coronary computed tomography angiography. Global longitudinal strain values were normal in 83.3% at enrollment and 94.2% at follow-up. Global longitudinal strain values were not associated with a positive SE at enrollment (GLS= -21.5% positive SE vs GLS= -19.9% negative SE, P=.443) or follow-up (GLS= -23.2% positive SE vs GLS= -23.1% negative SE, P=.859). Significant change in GLS was not associated with positive SE in follow-up (P=.401). Regional strain was not associated with colocalizing ischemia at enrollment or follow-up. Changes in GLS and number of ischemic segments from enrollment to follow-up showed a modest but not clinically meaningful correlation (β=0.41; 95% CI, 0.16, 0.67; P=.002). In this cohort of INOCA patients, resting GLS values were largely normal and did not associate with the presence, severity, or location of stress-induced ischemia. These findings may suggest the absence of subclinical myocardial dysfunction detectable by echocardiographic strain analysis at rest in INOCA.

Symptom Presentation among Women with Suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA).

Identifying ischemic heart disease (IHD) in women based on symptoms is challenging. Women are more likely to endorse non-cardiac symptoms. More than 50% of women with suspected ischemia have no obstructive coronary disease (and thus, INOCA) and impaired outcomes during follow-up. We aimed to identify symptoms having predictive capacity for INOCA in women with clinical evidence of coronary ischemia. We included 916 women from the original WISE cohort (NCT00000554) who had coronary angiography performed for suspected ischemia and completed a 65-item WISE symptom questionnaire. Sixty-two percent (n = 567) had suspected INOCA. Logistic regression models using a best subsets approach were examined to identify the best predictive model for INOCA based on Score χ2 and AICc. A 10-variable, best-fit model accurately predicted INOCA (AUC 0.72, 95% CI 0.68, 0.75). The model indicated that age ≤ 55 years, left side chest pain, chest discomfort, neck pain, and palpitations had independent, positive relationship (OR > 1) to INOCA (p < 0.001 to 0.008). An inverse relationship (OR < 1) was observed for impending doom, and pain in the jaw, left or bilateral arm, and right hand, interpreted as INOCA associated with the absence of these symptoms (p ≤ 0.001 to 0.023). Our best-fit model accurately predicted INOCA based on age and symptom presentation ~72% of the time. While the heterogeneity of symptom presentation limits the utility of this unvalidated 10-variable model, it has promise for consideration of symptom inclusion in future INOCA prediction risk modeling for women with evidence of symptomatic ischemia.

Illness Perception and the Impact of a Definitive Diagnosis on Women With Ischemia and No Obstructive Coronary Artery Disease: A Qualitative Study.

Ischemia and no obstructive coronary artery disease (INOCA) disproportionately impacts women, yet the underlying pathologies are often not distinguished, contributing to adverse health care experiences and poor quality of life. Coronary function testing at the time of invasive coronary angiography allows for improved diagnostic accuracy. Despite increased recognition of INOCA and expanding access to testing, data lack on first-person perspectives and the impact of receiving a diagnosis in women with INOCA. From 2020 to 2021, we conducted structured telephone interviews with 2 groups of women with INOCA who underwent invasive coronary angiography (n=29) at Yale New Haven Hospital, New Haven, CT: 1 group underwent coronary function testing (n=20, of whom 18 received a mechanism-based diagnosis) and the other group who did not undergo coronary function testing (n=9). The interviews were analyzed using the constant comparison method by a multidisciplinary team. The mean age was 59.7 years, and 79% and 3% were non-Hispanic White and non-Hispanic Black, respectively. Through iterative coding, 4 themes emerged and were further separated into subthemes that highlight disease experience aspects to be addressed in patient care: (1) distress from symptoms of uncertain cause: symptom constellation, struggle for sensemaking, emotional toll, threat to personal and professional identity; (2) a long journey to reach a definitive diagnosis: self-advocacy and fortitude, healthcare interactions brought about further uncertainty and trauma, therapeutic alliance, sources of information; (3) establishing a diagnosis enabled a path forward: relief and validation, empowerment; and (4) commitment to promoting awareness and supporting other women: recognition of sex and racial/ethnic disparities, support for other women. Insights about how women experience the symptoms of INOCA and their interactions with clinicians and the healthcare system hold powerful lessons for more patient-centered care. A coronary function testing-informed diagnosis greatly influences the healthcare experiences, quality of life, and emotional states of women with INOCA.

E-6 | Diagnostic Yield of Invasive Coronary Function Testing Compared With Coronary Angiography Alone in Women With Stable Ischemic Heart Disease

Objective: The aim of this study was to compare the diagnostic yield of invasive coronary function testing (CFT) and coronary angiography (CA) alone in women who presented with stable ischemic heart disease (SIHD). SIHD is a leading cause of morbidity and mortality in women, and women are more likely than men to suffer from ischemia and no obstructive coronary artery disease (INOCA). Endotypes of INOCA such as coronary vasospasm and microvascular dysfunction are not identified by routine coronary angiography. As a result, many women who undergo cardiac catheterization for suspected SIHD are not given a specific diagnosis or a targeted therapeutic plan. The diagnostic yield of CFT in comparison with CA alone in women has not been well-established. We conducted a retrospective study of women who presented with symptoms of SIHD. The primary outcome was post-procedure diagnosis identified after invasive CFT or CA. Secondary outcomes included post procedure change in cardiac medications and complications. A total of 133 women were evaluated, including 61 in the CFT group and 72 in the CA group. Compared to the CA group, women in the CFT group were more likely to receive a diagnosis of microvascular dysfunction 41% (n=25) vs. 3% (n=2), vasospastic angina 20% (n=12) vs. 1% (n=1), or endothelial dysfunction (n=5, 8% vs 0%). Other diagnoses in the CFT group included elevating resting flow (n=2), myocardial bridging (n=3), or mixed syndromes (n=5). In the CA group, women most commonly received a diagnosis of normal coronary arteries (n=15, 21%), non-obstructive coronary artery disease (n=54, 75%), or other (n=2, 3%). Post-procedure medication changes were more frequent in the CFT group compared to the CA group (69% vs 43%, p<0.001). In this study of women with SIHD, CFT confirmed an underlying vasomotor disorder in 85% of cases, whereas CA only reported a diagnosis of normal coronary arteries or non-obstructive CAD. CFT was able to further categorize women as having microvascular dysfunction or vasospastic angina, resulting in a higher frequency of post-procedure medication changes compared to CA alone. These findings suggest that CFT should be considered routinely in the evaluation of women with suspected SIHD.

The prognostic value of CZT SPECT myocardial blood flow (MBF) quantification in patients with ischemia and no obstructive coronary artery disease (INOCA): a pilot study

BackgroundDespite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients.MethodsThe study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina.ResultsDuring a median follow-up of 15 months (interquartile range (IQR) 11–20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) (p<0.001) and coronary flow reserve (CFR) (p<0.001) were significantly lower in the MACE group. Optimal thresholds of sMBF<3.16 and CFR<2.52 were extracted from the ROC curves, and both impaired sMBF (HR: 15.08; 95% CI 2.95–77.07; p=0.001) and CFR (HR: 6.51; 95% CI 1.43–29.65; p=0.01) were identified as prognostic factors for MACEs. Only sMBF<3.16 (HR: 11.20; 95% CI 2.04–61.41; p=0.005) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06, p=0.02; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10).ConclusionThe preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention.

Abstract 15367: Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women With Suspected Myocardial Ischemia: The Women’s Ischemia Syndrome Evaluation (WISE &amp; WISE-CVD) Projects

Introduction: Ischemic Heart Disease (IHD) risk in women includes biomedical, behavioral, and psychosocial contributors. Among psychosocial contributors, recent studies suggest that depression, especially somatic symptoms of depression such as anhedonia and low energy, may play a disproportionate role in the development of both IHD risk factors and major adverse cardiovascular events (MACE). Methods: We examined relationships between cognitive/somatic symptoms of depression and metabolic syndrome (MetS) in two independent cohorts of women with suspected IHD. In the Women’s Ischemia Syndrome Evaluation (WISE, NCT00000554), we also examined depression and MetS as predictors of all-cause mortality and MACE over a median 9.3-year follow-up. The sample from WISE included 641 women with suspected ischemia with or without obstructive coronary artery disease (CAD). The WISE-Coronary Vascular Dysfunction (WISE-CVD, NCT00832702) consisted of 359 women with suspected ischemia and no obstructive CAD (INOCA). Somatic, cognitive, and total depressive symptoms were measured via the Beck Depression Inventory (BDI). MetS was assessed according to the AHA’s ATP-III criteria. Results: (See attached table) In both the WISE and WISE-CVD samples, somatic symptoms of depression were associated with MetS diagnosis and MetS severity, while cognitive symptoms were not. Within the WISE sample, using Cox Proportional Hazard Regression, both somatic symptoms and MetS diagnosis were significant predictors of all-cause mortality and MACE, while cognitive symptoms were not. Conclusions: In two independent samples of women undergoing coronary angiography for suspected myocardial ischemia, somatic symptoms of depression were uniquely associated with both MetS and all-cause mortality and MACE, and both somatic symptoms of depression and MetS independently predicted all-cause mortality and MACE.

Magnetocardiography as a noninvasive diagnostic strategy for suspected coronary microvascular dysfunction

Abstract Background Coronary microvascular dysfunction (CMD) is increasingly recognized as an independent predictor of mortality with a 4-fold higher risk. However current diagnostic modalities are limited by the need for an invasive procedure, access, cost, and exposure of ionizing radiation. Purpose To investigate the ability of magnetocardiography (MCG) to identify CMD in patients with suspected ischemia and no obstructive coronary artery disease (INOCA). Methods This is an observational, prospective pilot study of patients scheduled for coronary functional angiography (CFA), gold standard for evaluation for CMD (defined as coronary flow reserve (CFR) ≤2). 13 patients underwent both CFA and a noninvasive 36-channel MCG scan. A machine learning model was developed to characterize the presence of CMD in these patients against age matched controls (AMCs). The model consists of a logistic regression classifier which takes features representing the relative strengths of the “characteristic dipoles” of the MCG scan as input. The characteristic dipoles are parameterizations of the three strongest magnetic field map components resulting from a singular value decomposition of the MCG signal. A total of 37 patients were included in this analysis including 13 patients who completed CFA (7 had CMD and 6 had CFR &amp;gt;2 and included in the AMCs group). An additional 24 asymptomatic, healthy patients that did not undergo CFR were also included in the AMC group. Results The mean age for AMCs was 57 years (70% women) and mean age for CMD patients was 54 years (100% women). The performance of the model was evaluated using repeated stratified cross-validation with 5 folds and 3 repeats, resulting in 15 different 80%/20% train/test splits. Figure 1 shows the distribution of samples belonging to the CMD and AMC groups in a 2-dimensional representation of the feature space. The clear separation of the two groups and the clustering of the AMCs demonstrates the ability of the model to identify patients with CMD. We found that MCG had a mean accuracy of 94.8% (±6.4%), sensitivity of 100% (±0.0%) and specificity of 93.3% (±8.2%) for the detection of CMD using gold standard CFR ≤2 as reference. Conclusion(s) First study to show that MCG can be used with 94.8% accuracy to identify CMD among patients suspicious for INOCA with no exposure to ionization, 90 seconds of scan time and minimal cost. The use of this noninvasive modality to identify CMD warrants further investigation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Genetesis

D-10 | Procedural Characteristics of Patients with Ischemia and No Obstructive Disease Undergoing Invasive Coronary Physiology Testing

Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and recent guidelines recommend invasive coronary physiology testing for evaluation of chest pain in selected patients. However, this is not routinely performed in clinical practice. We report the procedural characteristics of patients with INOCA who underwent clinically indicated invasive coronary physiology assessment.

A Left Ventricular Mechanical Dyssynchrony-Based Nomogram for Predicting Major Adverse Cardiac Events Risk in Patients With Ischemia and No Obstructive Coronary Artery Disease.

BackgroundThe risk stratification of patients with ischemia and no obstructive coronary artery disease (INOCA) remains suboptimal. This study aims to establish a left ventricular mechanical dyssynchrony (LVMD)-based nomogram to improve the present situation.MethodsPatients with suspected coronary artery disease (CAD) were retrospectively enrolled and divided into three groups: normal (stenosis <50%, without myocardial ischemia), INOCA (stenosis <50%, summed stress score >4, summed difference score ≥2), and obstructive CAD (stenosis ≥50%). LVMD was defined by ROC analysis. INOCA group were followed up for the occurrence of major adverse cardiac events (MACEs: cardiovascular death, non-fatal myocardial infarction, revascularization, stroke, heart failure, and hospitalization for unstable angina). Nomogram was established using multivariate Cox regression analysis.ResultsAmong 334 patients (118 [35.3%] INOCA), LVMD parameters were significantly higher in INOCA group versus normal group but they did not differ between obstructive CAD groups. In INOCA group, 27 (22.9%) MACEs occurred during a 26-month median follow-up. Proportion of LVMD was significantly higher with MACEs under both stress (63.0% vs. 22.0%, P < 0.001) and rest (51.9% vs. 20.9%, P = 0.002). Kaplan–Meier analysis revealed significantly higher rate of MACEs (stress log-rank: P = 0.002; rest log-rank: P < 0.001) in LVMD patients. Multivariate Cox regression analysis showed that stress LVMD (HR: 3.82; 95% CI: 1.30–11.20; P = 0.015) was an independent predictor of MACEs. The internal bootstrap resampling approach indicates that the C-index of nomogram was 0.80 (95% CI: 0.71–0.89) and the AUC values for 1 and 3 years of risk prediction were 0.68 (95% CI: 0.46–0.89) and 0.84 (95% CI: 0.72–0.95), respectively.ConclusionLVMD-based nomogram might provide incremental prognostic value and improve the risk stratification in INOCA patients.

Reduced myocardial perfusion is common among subjects with ischemia and no obstructive coronary artery disease and heart failure with preserved ejection fraction: a report from the WISE-CVD continuation study.

Aim:Women with evidence of ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiac events, including heart failure with preserved ejection fraction (HFpEF). To investigate potential links between INOCA and HFpEF, we examined pathophysiological findings present in both INOCA and HFpEF.Methods:We performed adenosine stress cardiac magnetic resonance imaging (CMRI) in 56 participants, including 35 women with suspected INOCA, 13 women with HFpEF, and 8 reference control women. Myocardial perfusion imaging was performed at rest and with vasodilator stress with intravenous adenosine. Myocardial perfusion reserve index was quantified as the ratio of the upslope of increase in myocardial contrast at stress vs. rest. All CMRI measures were quantified using CVI42 software (Circle Cardiovascular Imaging Inc). Statistical analysis was performed using linear regression models, Fisher’s exact tests, ANOVA, or Kruskal-Wallis tests.Results:Age (P = 0.007), Body surface area (0.05) were higher in the HFpEF group. Left ventricular ejection fraction (P = 0.02) was lower among the INOCA and HFpEF groups than reference controls after age adjustment. In addition, there was a graded reduction in myocardial perfusion reserve index in HFpEF vs. INOCA vs. reference controls (1.5 ± 0.3, 1.8 ± 0.3, 1.9 ± 0.3, P = 0.02), which was attenuated with age-adjustment.Conclusion:Reduced myocardial perfusion reserve appears to be a common pathophysiologic feature in INOCA and HFpEF patients.

Ultra-high sensitivity cardiac troponin-I concentration and left ventricular structure and function in women with ischemia and no obstructive coronary artery disease

AimsWomen are disproportionally impacted by ischemia and no obstructive coronary artery disease (INOCA), and such women are at increased risk of developing heart failure with preserved ejection fraction (HFpEF), however the mechanisms linking these conditions remain poorly understood. The aim of this study was to determine whether ultra-high sensitivity cardiac troponin I (u-hscTnI), an indicator of cardiomyocyte injury, is associated with abnormalities in myocardial perfusion and left ventricular (LV) structure and function in women with INOCA. Methods327 women with INOCA enrolled in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study underwent vasodilator stress cardiac magnetic resonance imaging (CMRI) and u-hscTnI measurements (Simoa HD-1 Analyzer, Quanterix Corporation). Multivariable linear regression was used to evaluate associations between u-hscTnI concentrations and myocardial perfusion (MPRI), LV mass index and feature-tracking derived strain measures of LV function. Resultsu-hscTnI concentrations were quantifiable in 100% of the cohort and ranged from 0.004 to 79.6 pg/mL. In adjusted models, u-hscTnI was associated with LV mass index (+2.03; 95% CI 1.17, 2.89; p < 0.01) and early diastolic radial strain rate (SR) (+0.13; 95% CI 0.01, 0.25; p = 0.03), early diastolic circumferential SR (−0.04; 95% CI −0.08, 0.002; p = 0.06) and early diastolic longitudinal SR (−0.03; 95% CI −0.07, 0.002; p = 0.06). u-hscTnI was not associated with MPRI (p = 0.39) in adjusted models. ConclusionTogether, these findings support cardiomyocyte injury as a putative pathway towards adverse LV remodeling and dysfunction; however, further research is needed to define the specific mechanism(s) driving myocellular injury in INOCA.

Peripheral microvascular dysfunction is also present in patients with ischemia and no obstructive coronary artery disease (INOCA).

In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = -0.38, p < 0.05), ET-1 (r = -0.73, p < 0.05) and CRP (r = -0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = -0.42, p < 0.05) and ET-1 (r = -0.48, p < 0.05). The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation.

Prognostic value of myocardial perfusion imaging with D-SPECT camera in patients with ischemia and no obstructive coronary artery disease (INOCA)

BackgroundMyocardial perfusion imaging (MPI) with a novel D-SPECT camera maintains excellent prognostic value compared to conventional SPECT. However, information about the relationship between D-SPECT MPI and the prognosis in patients with ischemia and no obstructive coronary artery disease (INOCA) is limited. The objective of this study was to evaluate the prognostic value of MPI with D-SPECT in INOCA and obstructive coronary artery disease (CAD) patients. MethodsAll consecutive patients with suspected CAD and without prior CAD who underwent D-SPECT MPI and invasive coronary angiography within 3 months were considered. INOCA and obstructive CAD were defined as < 50% and ≥ 50% coronary stenosis, respectively. Patients were followed-up for the occurrence of major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, stroke, heart failure and angina-related rehospitalization). ResultsAmong 506 patients, 232 (45.8%) were INOCA patients. A total of 33.2% of the INOCA patients had abnormal D-SPECT MPI, whereas 77.7% of the obstructive CAD patients had abnormal D-SPECT MPI. In both groups, patients with abnormal D-SPECT MPI demonstrated higher MACE rates and lower survival free of MACE. In addition, patients with INOCA and abnormal D-SPECT MPI had a poor prognosis similar to that of the obstructive CAD patients. Cox regression analysis showed that the risk-adjusted hazard ratios for abnormal D-SPECT MPI were 2.55 [1.11-5.87] and 2.06 [1.03-4.10] in the INOCA and obstructive CAD patients, respectively. ConclusionsD-SPECT MPI provides excellent prognostic information, with a more severe prognosis in patients with abnormal D-SPECT MPI. INOCA patients with abnormal D-SPECT MPI experience a poor prognosis similar to that of patients with obstructive CAD.

Abstract 11244: Illness Perception and the Impact of a Definitive Diagnosis on Women with Ischemia Without Obstructive Coronary Artery Disease: A Qualitative Study

Introduction: Women are more likely to have ischemia and no obstructive coronary artery disease (INOCA), and the underlying pathologies of this diagnosis (such as microvascular dysfunction and coronary vasospasm) are often not distinguished. Comprehensive invasive physiology testing at the time of invasive coronary angiography (ICA) allows for improved diagnostic accuracy. However, despite increased recognition of INOCA and expanding access to testing, data lacks on the impact of receiving a mechanism-based, definitive diagnosis (DD) on women. Methods: We are conducting in-depth telephone interviews with women with INOCA who recently underwent ICA. Respondents are asked about understanding of diagnosis, healthcare experiences, and health status prior to and following ICA. The interviews are transcribed and analyzed using the constant comparison method. Results: To date, 17 women were interviewed (median age: 55), 14 of whom underwent physiology testing and 13 of whom received a DD. Through iterative coding, four major themes emerged: (1) Illness perception and communication: A DD equipped women with a better understanding of their symptoms and subsequent functional status and provided tools for communication; (2) Psychological toll: A DD relieved frustration with repeated testing, lack of validation, and fear about prognosis; (3) Identity: A DD served as a turning point for reclaiming their personal and professional identity; (4) Lifestyle changes and outlook: A DD brought relief and hope for the future and motivation for a healthier lifestyle. See quotes in Table. Conclusions: Women with INOCA were eager to share experiences (89% participated). Overall, they described the physical, emotional, interpersonal, and financial toll of seeking a diagnosis for their symptoms. Those who received a DD reported better understanding of disease, healthcare experiences, and well-being. Next steps are to continue interviews until thematic saturation is reached.