Vasodilator Stress Cardiac Magnetic Resonance Research Articles

Comparison of the diagnostic accuracy of dynamic CT perfusion and cardiac CMR with quantitative perfusion: a subanalysis of ADVANTAGE II study

Abstract Funding Acknowledgements Type of funding sources: None. Background The ADVANTAGE II study has evaluated the performance of dynamic myocardial perfusion assessed by CT (CTP) in stented patient using ICA and in particular invasive coronary physiology (FFR and IMR) as gold-standard. Recently, quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been showed to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD). In a substudy of ADVANTAGE II we aimed to evaluate the performance of quantitative stress CMR in comparison to CTP. Methods We present data from 39 subjects with clinically indicated ICA who underwent both vasodilator stress CMR using 1.5T MR scanner (General Electric) and dynamic stress myocardial CTP using a last generation scanner characterized by a 16-cm Z-axis coverage. In CMR Quantitative myocardial perfusion imaging was performed using the dual sequence technique (i.e. low-resolution slice for arterial input function and 2–3 short axis slices for myocardial perfusion). Resting MBF (rMBF), Stress MBF (sMBF), and myocardial perfusion reserve (MPR) were measured using Fermi deconvolution (Circle Cvi42). Quantitative perfusion results were displayed on color-encoded pixel-wise maps and on a 16-segment plot with segmental values listed. Results When FFR was used as gold standard the diagnostic accuracy of CTP was higher than those of CCTA (84.7% vs. 61.5%, p<0.001). When IMR was used as gold standard, diagnostic accuracy of CTP was higher than CCTA (82.9% vs. 59.3%, p<0.01, respectively). When the presence of at least one abnormal physiological parameter among FFR and IMR was used as gold standard, the diagnostic accuracy of CTP was higher than that of CCTA (90.8%vs 68%). Quantitative stress CMR using 2.2 ml/min/g as cut-off has a sensitivity of 83.3%, 77.7% and 100% vs QCA, FFR and IMR, respectively with higher performance of dynamic CTP in comparison to quantitative stress CMR. Conclusions In this substudy of ADVANTAGE II, we showed that global sMBF in MRI can accurately identify patients with CAD. Dynamic CTP seems to offer higher value of diagnostic performance in comparison to quantitative CMR that seems to be very promising, but more data are needed.

AI-Based Fully Automated Left Atrioventricular Coupling Index as a Prognostic Marker in Patients Undergoing Stress CMR

BackgroundThe left atrioventricular coupling index (LACI) is a strong and independent predictor of heart failure (HF) in individuals without clinical cardiovascular disease. Its prognostic value is not established in patients with cardiovascular disease. ObjectivesThis study sought to determine in patients undergoing stress cardiac magnetic resonance (CMR) whether fully automated artificial intelligence–based LACI can provide incremental prognostic value to predict HF. MethodsBetween 2016 and 2018, the authors conducted a longitudinal study including all consecutive patients with abnormal (inducible ischemia or late gadolinium enhancement) vasodilator stress CMR. Control subjects with normal stress CMR were selected using propensity score matching. LACI was defined as the ratio of left atrial to left ventricular end-diastolic volumes. The primary outcome included hospitalization for acute HF or cardiovascular death. Cox regression was used to evaluate the association of LACI with the primary outcome after adjustment for traditional risk factors. ResultsIn 2,134 patients (65 ± 12 years, 77% men, 1:1 matched patients [1,067 with normal and 1,067 with abnormal CMR]), LACI was positively associated with the primary outcome (median follow-up: 5.2 years [IQR: 4.8-5.5 years]) before and after adjustment for risk factors in the overall propensity-matched population (adjusted HR: 1.18 [95% CI: 1.13-1.24]), in patients with abnormal CMR (adjusted HR per 0.1% increment: 1.22 [95% CI: 1.14-1.30]), and in patients with normal CMR (adjusted HR per 0.1% increment: 1.12 [95% CI: 1.05-1.20]) (all P < 0.001). After adjustment, a higher LACI of ≥25% showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-index improvement: 0.16; net reclassification improvement = 0.388; integrative discrimination index = 0.153, all P < 0.001; likelihood ratio test P < 0.001). ConclusionsLACI is independently associated with hospitalization for HF and cardiovascular death in patients undergoing stress CMR, with an incremental prognostic value over traditional risk factors including inducible ischemia and late gadolinium enhancement.

Abstract 14447: Multi-Center Evaluation of Stress Myocardial Blood Flow by Cardiac Magnetic Resonance in Known and Suspected Ischemic Heart Disease: Preliminary Findings From the AQUA-MBF Initiative

Introduction: Quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in several mostly small, single-center studies. The AQUA-MBF ( A ssessment of QUA ntitative MBF ) study is a multicenter initiative involving 16 centers. Hypothesis: The goal of this sub-study is to determine if MBF can differentiate CAD, CMD, and normal volunteers in this multicenter setting. Methods: We present data from 53 subjects (15 with CAD, 20 at risk for CMD and 18 controls) who underwent vasodilator stress CMR (Figure) using 1.5T and 3.0T MR scanners (General Electric). At risk for CMD was defined as having diabetes and 2 other risk factors in absence of ≥50% stenosis based on coronary CT. CAD was defined as the presence of stenosis ≥70% based on invasive coronary angiography. Stress perfusion images were acquired using the dual sequence technique. Stress MBF was measured in each of the 16 AHA segments using Fermi deconvolution (Circle Cvi42). In the CAD group, each segment was further classified as having late gadolinium enhancement (LGE), supplied by CAD, or a normal remote territory. The means of the 5 groups were compared using one-way analysis of variance. Results: The segmental stress MBF (ml/g/min) for the 5 groups are shown in figure. Compared to the normal group, segmental stress MBF in 4 disease groups were significantly lower (p&lt;0.001). Segmental MBF in those at risk for CMD was lower than normal segments and greater than CAD segments (p&lt;0.001). LGE and CAD segments had the lowest stress MBF but similar to each other (p=0.9). Conclusions: In this multicenter study, we show that quantification of MBF using the dual sequence stress perfusion CMR technique can differentiate diseased from healthy myocardium and also between obstructive CAD and those at risk for CMD.

Risk of death associated with incident heart failure in patients with known or suspected chronic coronary syndrome.

Traditional adverse events in chronic coronary syndrome (CCS) include atherothrombotic events but usually exclude heart failure (HF). Data are scarce about how new-onset HF modifies mortality risk. We aimed to determine the incidence of HF and compare its long-term mortality risk with myocardial infarction (MI) and stroke in patients with known or suspected CCS. We prospectively evaluated 5811 consecutive HF-free patients submitted to vasodilator stress cardiac magnetic resonance (CMR) for known or suspected CCS. Ischaemic burden and left ventricular ejection fraction were assessed by CMR. HF included outpatient diagnosis or acute HF hospitalization. The mortality risk for the incident events and their cross-comparisons were evaluated using a Markov illness-death model with transition-specific survival models. The mean age was 55±11years, and 38.9% were female. At a median follow-up of 5.44 (IQR=2.53-8.55) years, 591 deaths were registered (1.79 per 100 P-Y). The rates of new-onset HF were higher compared with MI and stroke [1.02, 0.62, and 0.51, respectively (P<0.05)]. The adjusted association between new-onset HF, MI, and stroke, and subsequent mortality was time dependent. The risk increased almost linearly for HF and became significant by the third year. By Year 10, the mortality risk attributable to new-onset HF was more than 2.5-fold (HR: 2.68, 95% CI=1.74-4.12). For MI, there was a significant increase in mortality risk up to the second year, followed by a monotonic decrease. For stroke, the mortality risk increased for the entire follow-up but became significant by the third year. A cross-comparison among incident endpoints HF outnumbers risk for those with MI by the sixth year (HRyear6.3 : 1.88, 95% CI=1.03-3.43). There was no difference in mortality risk between incident HF and stroke. In patients with CCS, long-term rates of incident HF were higher than MI and stroke. Patients with new-onset HF showed a higher risk of long-term mortality.

Relation of Myocardial Perfusion Reserve and Left Ventricular Ejection Fraction in Ischemic and Nonischemic Cardiomyopathy

Quantification of myocardial perfusion reserve (MPR) using vasodilator stress cardiac magnetic resonance is increasingly used to detect coronary artery disease. However, MPR can also be altered because of changes in microvascular function. We aimed to determine whether MPR can distinguish between ischemic cardiomyopathy (IC) secondary to coronary artery disease and non-IC (NIC) with microvascular dysfunction and no underlying epicardial coronary disease. A total of 60 patients (mean age 65 ± 14 years, 30% women), including 31 with IC and 29 with NIC, were identified from a pre-existing vasodilator stress cardiac magnetic resonance registry. Short-axis cine slices were used to measure left ventricular ejection fraction (LVEF) using the Simpson method of disks. MPR index (MPRi) was determined from first-pass myocardial perfusion images during stress and rest using the upslope ratio, normalized for the arterial input and corrected for rate pressure product. Patients in both groups were divided into subgroups of LVEF ≤35% and LVEF >35%. Differences in MPRi between the subgroups were examined. MPRi was moderately correlated with LVEF in patients with NIC (r=0.53, p=0.03), whereas the correlation in patients with IC was lower (r=0.32, p=0.22). Average LVEF in NIC and IC was 34% ± 8% and 35% ± 8%, respectively (p=0.63). MPRi was not significantly different in IC compared with NIC (1.17 [0.88 to 1.61] vs 1.23 [1.07 to 1.66], p=0.41), including the subgroups of LVEF (IC: 1.20 ± 0.56 vs NIC: 1.15 ± 0.24, p=0.75 for LVEF ≤35% and IC: 1.35 ± 0.44 vs NIC: 1.58 ± 0.50, p=0.19 for LVEF >35%). However, MPRi was significantly lower in patients with LVEF ≤35% compared with those with LVEF>35% (1.17 ± 0.40 vs 1.47 ± 0.47, p=0.01). Similar difference between LVEF groups was noted in the patients with NIC (1.15 ± 0.24 vs 1.58 ± 0.50, p=0.006) but not in the patients with IC (1.20 ± 0.56 vs 1.35 ± 0.44, p=0.42). MPRi can be abnormal in the presence of left ventricular dysfunction with nonischemic etiology. This is a potential pitfall to consider when using this approach to detect ischemia because of epicardial coronary disease using myocardial perfusion imaging.

Phenotypic clustering of patients with newly diagnosed coronary artery disease using cardiovascular magnetic resonance and coronary computed tomography angiography

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Thus, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial. PURPOSE Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) data was used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD. METHODS Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. A cluster analysis was performed on clinical, CCTA and CMR variables, and associations between phenogroups and outcomes were assessed. RESULTS Of 2,210 patients who underwent CMR, 2,015 (46% male, mean 70 ± 12 years) completed follow-up (median 6.8[IQR 5.9-9.2] years); 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: [PG1] CAD in elderly patients with few traditional risk factors; [PG2] women with metabolic syndrome, calcified plaques on CCTA and preserved left ventricular ejection fraction (LVEF); and [PG3] younger male smokers with proximal noncalcified plaques on CCTA, myocardial scar and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality and all-cause mortality (all p &amp;lt; 0.001) differed among the three PG, PG3 having the worse prognosis. In each PG, inducible ischemia was associated with MACE (PG1, HR = 3.09, 95%CI, 1.70-5.62; PG2, HR = 3.62, 95%CI, 2.31-5.70; PG3, HR = 3.55, 95%CI, 2.30-5.49; all p &amp;lt; 0.001). CONCLUSIONS Cluster analysis of clinical, CCTA and CMR variables identified 3 phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Abstract Figure. Cluster analysis: Biplot representation Abstract Figure. Kaplan Meier curves by Phenogroups

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.

Long-term prognostic value of vasodilator stress cardiac magnetic resonance in patients with atrial fibrillation.

AimsAlthough the prevalence of coronary artery disease (CAD) is high among patients with atrial fibrillation (AF), studies on stress perfusion cardiac magnetic resonance (CMR) imaging frequently exclude patients with AF, and its prognostic and diagnostic value in high‐risk patients with suspected or known CAD remains unclear.Methods and resultsIn this longitudinal cohort study, we included 164 consecutive patients with AF during vasodilator perfusion CMR. Diagnostic value was evaluated regarding invasive coronary angiography in a subset of patients. We targeted a follow‐up of >5 years and used CMR results as stratification, and the primary outcome was major adverse cardiac events [MACE, cardiovascular (CV) death and myocardial infarction (MI)]. Secondary outcomes included late coronary revascularization or stroke and the components of the primary outcome. Of the whole cohort (73.8% male, mean age 72.2 years ± 7.8 SD), 99.4% were successfully scanned (163/164 patients). Median CHA2DS2‐VASc score was 4 [interquartile range (IQR) 3–5], and median 10‐year risk for CV events based on SMART risk score was high (24%, IQR 16–32%). Thirty‐two patients (19.6%) presented with ischaemia and 52 patients (31.9%) with late gadolinium enhancement (LGE). A combination of LGE and inducible ischaemia was present in 20 patients (12.3%). Diagnostic accuracy was 86.2% [confidence interval (CI) 68.3–96.1%]. The median follow‐up was 6.6 years (IQR 3.6–7.8). Ischaemia in vasodilator perfusion CMR was significantly associated with the occurrence of MACE [P < 0.01; hazard ratio (HR) 2.65, CI 1.39–5.08], as well as LGE (P = 0.03; 1.74, CI 1.07–3.64) and the combination of both (P < 0.01; HR 2.67, CI 1.59–5.62). After adjustment by age, left ventricular ejection fraction, and the presence of diabetes, ischaemia in vasodilator perfusion CMR remained significantly associated with the occurrence of MACE (2.10, CI 1.08–4.10; P = 0.03). In secondary endpoint analysis, there was a significant association of ischaemia in CMR with CV death (P < 0.05; HR 1.93, CI 0.95–3.9) and MI (P < 0.01; HR 13, CI 1.35–125.4), while no significant association was found regarding the occurrence of revascularization (P = 0.45; HR 1.43, CI 0.57–3.58) or stroke (P = 0.99; HR 0.99, CI 0.21–2.59).ConclusionsVasodilator stress perfusion CMR demonstrated an excellent diagnostic and significant prognostic value at long‐term follow‐up in high‐risk patients with persistent AF and suspected or known CAD.

Phenotypic Clustering of Patients With Newly Diagnosed Coronary Artery Disease Using Cardiovascular Magnetic Resonance and Coronary Computed Tomography Angiography.

Background: Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Therefore, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial.Objective: Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA), and cardiac magnetic resonance (CMR) data were used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD.Materials and Methods: Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. For this exploratory work, a cluster analysis was performed on clinical, CCTA, and CMR variables, and associations between phenogroups and outcomes were assessed.Results: Among 2,210 patients who underwent both CCTA and CMR, 2,015 (46% men, mean 70 ± 12 years) completed follow-up [median 6.8 (IQR 5.9–9.2) years], in which 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: (PG1) CAD in elderly patients with few traditional risk factors; (PG2) women with metabolic syndrome, calcified plaques on CCTA, and preserved left ventricular ejection fraction (LVEF); (PG3) younger men smokers with proximal non-calcified plaques on CCTA, myocardial scar, and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality, and all-cause mortality (all p < 0.001) differed among the three PG, in which PG3 had the worse prognosis. In each PG, inducible ischemia was associated with MACE [PG1, Hazards Ratio (HR) = 3.09, 95% CI, 1.70–5.62; PG2, HR = 3.62, 95% CI, 2.31–5.7; PG3, HR = 3.55, 95% CI, 2.3–5.49; all p < 0.001]. The study presented some key limitations that may impact generalizability.Conclusions: Cluster analysis of clinical, CCTA, and CMR variables identified three phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Whether automated unsupervised phenogrouping of CAD patients may improve clinical decision-making should be further explored in prospective studies.

AI Based CMR Assessment of Biventricular Function: Clinical Significance of Intervendor Variability and Measurement Errors

ObjectivesThe aim of this study was to determine whether left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) and left ventricular mass (LVM) measurements made using 3 fully automated deep learning (DL) algorithms are accurate and interchangeable and can be used to classify ventricular function and risk-stratify patients as accurately as an expert. BackgroundArtificial intelligence is increasingly used to assess cardiac function and LVM from cardiac magnetic resonance images. MethodsTwo hundred patients were identified from a registry of individuals who underwent vasodilator stress cardiac magnetic resonance. LVEF, LVM, and RVEF were determined using 3 fully automated commercial DL algorithms and by a clinical expert (CLIN) using conventional methodology. Additionally, LVEF values were classified according to clinically important ranges: <35%, 35% to 50%, and ≥50%. Both ejection fraction values and classifications made by the DL ejection fraction approaches were compared against CLIN ejection fraction reference. Receiver-operating characteristic curve analysis was performed to evaluate the ability of CLIN and each of the DL classifications to predict major adverse cardiovascular events. ResultsExcellent correlations were seen for each DL-LVEF compared with CLIN-LVEF (r = 0.83-0.93). Good correlations were present between DL-LVM and CLIN-LVM (r = 0.75-0.85). Modest correlations were observed between DL-RVEF and CLIN-RVEF (r = 0.59-0.68). A >10% error between CLIN and DL ejection fraction was present in 5% to 18% of cases for the left ventricle and 23% to 43% for the right ventricle. LVEF classification agreed with CLIN-LVEF classification in 86%, 80%, and 85% cases for the 3 DL-LVEF approaches. There were no differences among the 4 approaches in associations with major adverse cardiovascular events for LVEF, LVM, and RVEF. ConclusionsThis study revealed good agreement between automated and expert-derived LVEF and similarly strong associations with outcomes, compared with an expert. However, the ability of these automated measurements to accurately classify left ventricular function for treatment decision remains limited. DL-LVM showed good agreement with CLIN-LVM. DL-RVEF approaches need further refinements.

Downstream testing after exercise ECG stress test – can we predict ischemia on subsequent vasodilator stress cardiac magnetic resonance?

Abstract Background Exercise ECG stress test (ExECG) is useful in the diagnostic work-up of patients with chest pain and known or suspected stable ischemic heart disease (SIHD). However, current guidelines recommend a stress imaging, ischemia-detecting technique such as vasodilator stress cardiac magnetic resonance (vs-CMR) if available. Whether clinical and ExECG variables can predict ischemia on subsequent vs-CMR testing is unknown. Material and methods We retrospectively included 289 patients who underwent an ExECG and a subsequent vs-CMR in the year after this test and who didn't undergo a revascularization procedure in this time frame. Clinical, ExECG and vs-CMR variables were included in the registry. vs-CMR was considered positive if ischemia was evident in at least one myocardial segment on stress first-pass perfusion without concomitant necrosis on late gadolinium enhancement imaging. We performed univariate and multivariate analysis to check for the association of variables with the risk of ischemia on vs-CMR. Results Mean time from ExECG to vs-CMR was 97,27±88,31 days and 91 vs-CMR were positive for ischemia. Age, male sex, diabetes mellitus, hypertension, dyslipidaemia and personal history of ischemic heart disease, percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were predictors of ischemia on vs-CMR in the univariate analysis. On ExECG, time of exercise, exercise capacity, chest pain during ExECG, maximum heart rate (HR) and systolic blood pressure (SBP), % of predicted HR, chronotropic reserve index, maximum and reserve of double product and Duke Treadmill Score were also associated with ischemia on vs-CMR. However, the only independent predictors on multivariate binary logistic regression stepwise analysis were history of PCI (HR 3.79 [2.03–7.09], p&amp;lt;0.001) or CABG (HR 5.57 [1.80–17.26], p=0.003), maximum double product (HR 0.94 [0.90–0.99] per 1000 increase, p=0.02) and Duke Treadmill Score (HR 0.95 [0.91–0.99], p=0.019). Subgroup analysis showed that male sex (HR 1.95 [1.16–3.28], p=0.012), history of ischemic heart disease (HR 4.73 [2.88–7.76], p&amp;lt;0.001) and maximum double product (HR 0.94 [0.90–0.98] per 1000 increase, p=0.006) were predictors of ischemia on vs-CMR in non-revascularized patients (n=212). In revascularized patients (n=77) the only independent predictor was the Duke Treadmill Score on ExECG (HR 0.93 [0.86–0.99], p=0.048). Conclusions Several ExECG variables, namely Duke Treadmill Score and parameters of myocardial oxygen consumption such as maximum doble product, can predict the risk of ischemia on subsequent vs-CMR in revascularized and non-revascularized patients with chest pain. This can help select patients who should undergo vs-CMR afeter ExECG for ischemia detection. Funding Acknowledgement Type of funding sources: None.

Sex differences on new-onset heart failure in patients with known or suspected chronic coronary syndrome

Abstract Background The impact of sex in patients with chronic coronary syndrome (CCS) has been widely reported, but little is known about the influence of sex on the risk of new-onset HF in patients with CCS. Objectives We aimed to examine sex-related differences and new-onset heart failure (HF) risk in patients with known or suspected CCS undergoing vasodilator stress cardiac magnetic resonance (CMR). Methods We prospectively evaluated 5,899 consecutive HF-free patients submitted to stress CMR for known or suspected CCS. Ischemic burden (number of segments with stress-induced perfusion deficit) and left ventricular ejection fraction (LVEF) were assessed by CMR. The association between sex and new-onset HF (including outpatient diagnosis or acute HF hospitalization) was evaluated using a Cox proportional-hazards regression model adjusted for competing events (death, myocardial infarction, and non-CMR-related revascularization). Results A total of 2,289 (38.8%) patients were women, and 539 (9.1%) underwent CMR-related revascularization. During a median follow-up of 4.5 years, 610 (10.3%) patients died, 191 (3.2%) suffered a myocardial infarction, 420 (7.1%) underwent CMR-non-related revascularization, and 314 (5.3%) developed new-onset HF. Unadjusted new-onset HF rates were higher in women than in men (1.25 vs 0.83 per 100 person/years, p=0.002) (Figure 1). After comprehensive multivariate adjustment, women showed an increased risk of new-onset HF (HR=1.61, 95% CI: 1.21–2.13, p=0.001). Compared with men, the risk of new-onset HF was higher in women with LVEF &amp;gt;53%. Conclusions Compared with men, women with CCS are at a higher risk of new-onset HF. Further studies are needed to unravel the mechanisms behind these sex-related differences. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) Figure 1

Exercise ECG testing in patients without known ischemic heart disease: predictors of ischemia of downstream vasodilator stress cardiac magnetic resonance

Abstract Background In routine clinical practice, patients with chest pain and suspected stable ischemic heart disease (SIHD) usually undergo an exercise ECG stress test (ExECG) for ischemia detection. However, since the sensitivity of this technique is relatively low, concerns exist that many patients could remain underdiagnosed. We intend to assess the clinical and ExECG predictors of ischemia on subsequent vasodilator stress cardiac magnetic resonance (vs-CMR) to help select which patients should undergo downstream testing after an initial ExECG. Material and methods We retrospectively included 197 patients without previous history of ischemic heart disease who underwent an ExECG and a subsequent vs-CMR in the year after this test and who didn't undergo a revascularization procedure in this time frame. Clinical, ExECG and vs-CMR variables were included in the registry. vs-CMR was considered positive if ischemia was evident in at least one myocardial segment on stress first-pass perfusion without concomitant necrosis on late gadolinium enhancement imaging. We performed univariate and multivariate analysis to check for the association of variables with the risk of ischemia on vs-CMR. Results Mean time from ExECG to vs-CMR was 88.69±84.32 days and 37 vs-CMR were positive for ischemia. Male sex, less exercise time, less % of maximum predicted exercise capacity, less maximum double product (heart rate x systolic blood pressure) and less double product reserve (DPR = maximum double product - basal double product) were associated with ischemia on vs-CMR on univariate analyses. However, the only independent predictors of ischemia on vs-CMR on multivariate binary logistic regression were male sex (HR 2.62 [CI 95%: 1.13–5.76], p=0.016) and less DPR (HR 0.90 [CI 95%: 0.84–0.97] per 1000 increase, p=0.006). The risk score derived from these two variables had a moderate predictive power (ROC curves, AUC 0.657, p=0.003). The best cut-off point for the DPR was 12400, as derived from the Youden index. It allowed stratification of the risk of ischemia on vs-CMR, which ranged from 9% in women with &amp;gt;12400 DPR, 18.8% in men with &amp;gt;12400 DPR, 24.1% in women with ≤12400 DPR to 42.9% in men with ≤12400 DPR (p=0.005, Figure 1). Conclusions Male sex and less double product reserve on ExECG can moderately predict the risk of ischemia on subsequent vs-CMR in patients presenting with chest pain and without previous SIHD. This can help select patients who benefit most from vs-CMR for diagnostic purposes. Funding Acknowledgement Type of funding sources: None. Figure 1

Exercise ECG Testing and Stress Cardiac Magnetic Resonance for Risk Prediction in Patients With Chronic Coronary Syndrome.

Vasodilator stress cardiac magnetic resonance (VS-CMR) has become crucial in the workup of patients with known or suspected chronic coronary syndrome (CCS). Whether traditional exercise ECG testing (ExECG) contributes prognostic information beyond VS-CMR is unclear. We retrospectively included 288 patients with known or suspected CCS who had undergone ExECG and subsequent VS-CMR in our institution. Clinical, ExECG, and VS-CMR variables were recorded. We defined the serious adverse events (SAE) as a combined endpoint of acute coronary syndrome, admission for heart failure, or all-cause death. During a mean follow-up of 4.2 ± 2.15 yr, we registered 27 SAE (15 admissions for acute coronary syndrome, eight admissions for heart failure, and four all-cause deaths). Once adjusted for clinical, ExECG, and VS-CMR parameters associated with SAE, the only independent predictors were HRmax in ExECG (HR = 0.98: 95% CI, 0.96-0.99; P = .01) and more extensive stress-induced perfusion defects (PDs, number of segments) in VS-CMR (HR = 1.19: 95% CI, 1.07-1.34; P < .01). Adding HRmax significantly improved the predictive power of the multivariable model for SAE, including PDs (continuous reclassification improvement index: 0.47: 95% CI, 0.10-0.81; P < .05). The annualized SAE rate was 1% (if PD < 2 segments and HRmax > 130 bpm), 2% (if PD < 2 segments and HRmax ≤ 130 bpm), 3.2% (if PD ≥ 2 segments and HRmax > 130 bpm), and 6.3% (if PD ≥ 2 segments and HRmax ≤ 130 bpm), P < .01, for the trend. In patients on β-blocker therapy, however, only PDs in VS-CMR, but not HRmax, predicted SAE. We conclude that ExECG contributes significantly to prognostic information beyond VS-CMR in patients with known or suspected CCS.

Stress cardiac magnetic resonance for mortality prediction and decision-making: registry of 2496 elderly patients with chronic coronary syndrome

Introduction and objectivesThe management of elderly patients with chronic coronary syndrome (CCS) is challenging. We explored the prognostic value and usefulness for decision-making of ischemic burden determined by vasodilator stress cardiac magnetic resonance (CMR) imaging in elderly patients with known or suspected CCS. MethodsThe study group comprised 2496 patients older than 70 years who underwent vasodilator stress CMR for known or suspected CCS. The ischemic burden (number of segments with stress-induced perfusion deficit) was calculated following the 17-segment model. Subsequently, we retrospectively analyzed its association with all-cause mortality and the effect of CMR-guided revascularization. ResultsDuring a median follow-up of 4.58 years, there were 430 deaths (17.2%). A higher ischemic burden was an independent predictor of mortality (HR, 1.04; 95%CI, 1.01-1.07 for each additional ischemic segment; P=.006). This association was also found in patients older than 80 years and in women (P <.001). An interaction between revascularization and mortality was detected toward deleterious consequences at low ischemic burden and a protective effect in patients with extensive ischemia. ConclusionsVasodilator stress CMR is a valuable tool to stratify risk in elderly patients with CCS and might be helpful to guide decision-making in this scenario.

Resonancia magnética cardiaca de estrés para predecir mortalidad y toma de decisiones: registro de 2.496 pacientes mayores con síndrome coronario crónico

Introduction and objectivesThe management of elderly patients with chronic coronary syndrome (CCS) is challenging. We explored the prognostic value and usefulness for decision-making of ischemic burden determined by vasodilator stress cardiac magnetic resonance (CMR) imaging in elderly patients with known or suspected CCS. MethodsThe study group comprised 2496 patients older than 70 years who underwent vasodilator stress CMR for known or suspected CCS. The ischemic burden (number of segments with stress-induced perfusion deficit) was calculated following the 17-segment model. Subsequently, we retrospectively analyzed its association with all-cause mortality and the effect of CMR-guided revascularization. ResultsDuring a median follow-up of 4.58 years, there were 430 deaths (17.2%). A higher ischemic burden was an independent predictor of mortality (HR, 1.04; 95%CI, 1.01-1.07 for each additional ischemic segment; P=.006). This association was also found in patients older than 80 years and in women (P <.001). An interaction between revascularization and mortality was detected toward deleterious consequences at low ischemic burden and a protective effect in patients with extensive ischemia. ConclusionsVasodilator stress CMR is a valuable tool to stratify risk in elderly patients with CCS and might be helpful to guide decision-making in this scenario.Full English text available from: www.revespcardiol.org/en

Stress cardiovascular magnetic resonance and mortality in a registry of 2496 elderly patients with chronic coronary syndrome. Prognosis and decision-making

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER) Introduction and objectives. Management of the elderly with chronic coronary syndrome (CCS) is challenging. We explore the prognostic value and the usefulness for decision-making of the ischemic burden determined by vasodilator stress cardiac magnetic resonance (CMR) imaging in elderly patients with known or suspected CCS. Methods. The study group was made up of 2496 patients older than 70 years submitted to vasodilator stress CMR for known or suspected CCS. The ischemic burden (number of segments with stress-induced perfusion deficit) was calculated following the 17-segment model. Its association with all-cause mortality and the effect of CMR-guided revascularization were analyzed retrospectively. Results. During a median follow-up of 4.58 years, 430 deaths (17.2%) were recorded. A larger ischemic burden was an independent predictor of mortality: hazard ratio [95% confidence intervals]: 1.04 [1.01-1.07] for each additional ischemic segment, p = 0.006). This association also occurred in patients over 80 years of age and in women (p &amp;lt; 0.001). Compared to non-revascularized patients, revascularization associated with worse outcomes at low ischemic burden and exerted protective prognostic effect in patients with extensive ischemia both in the whole group (p for interaction = 0.003) and in 496 patients matched 1:1 by a propensity score (p = 0.06). Conclusions. Vasodilator stress CMR represents a valuable tool to stratify risk in elderly patients with CCS and might be helpful to guide decision-making in this scenario.

Sex differences on new-onset heart failure in patients with known or suspected coronary artery disease.

The impact of sex in patients with CAD has been widely reported, but little is known about the influence of sex on the risk of new-onset HF in patients with known or suspected CAD. We aimed to examine sex-related differences and new-onset heart failure (HF) risk in patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress cardiac magnetic resonance (CMR). We prospectively evaluated 5899 consecutive HF-free patients submitted to stress CMR for known or suspected CAD. Ischaemic burden (number of segments with stress-induced perfusion deficit) and left ventricular ejection fraction (LVEF) were assessed by CMR. The association between sex and new-onset HF (including outpatient diagnosis or acute HF hospitalization) was evaluated using a Cox proportional hazards regression model adjusted for competing events [death, myocardial infarction (MI), and revascularization]. A total of 2289 (38.8%) patients were women. During a median follow-up of 4.5 years, 610 (10.3%) patients died, 191 (3.2%) suffered an MI, 905 (15.3%) underwent revascularization, and 314 (5.3%) developed new-onset HF. Unadjusted new-onset HF rates were higher in women than in men (1.25 vs. 0.83 per 100 person-years, P = 0.001). After comprehensive multivariate adjustment, women showed an increased risk of new-onset HF (hazard ratio 1.58, 95% confidence interval 1.18-2.10; P = 0.002). We found a sex-differential effect along the continuum of LVEF (P-value for interaction = 0.007). At lower LVEF, there was an increased risk in both sexes. However, compared with men, the risk of new-onset HF was higher in women with LVEF >55%. Women with known or suspected CAD are at a higher risk of new-onset HF. Further studies are needed to unravel the mechanisms behind these sex-related differences.

Additional prognostic value of vasodilator stress CMR in patients with inconclusive stress test to detect coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Guidelines recommend performing a non-invasive testing for ischemia to diagnose coronary artery disease (CAD). However, these tests are frequently inconclusive (25%). This population has been poorly studied because of its heterogeneity. In such cases, stress cardiac magnetic resonance (CMR) may be useful to improve diagnostic certainty. To date, no study has evaluated the prognostic value of stress CMR in these patients presenting with prior inconclusive test. PURPOSE To assess the additional prognostic value of vasodilator stress perfusion CMR in patients with a first inconclusive stress test to detect CAD. METHODS Between 2008 and 2018, consecutive patients with inconclusive stress test prospectively referred for vasodilator stress perfusion CMR with dipyridamole were followed for major adverse cardiovascular events (MACE) defined as cardiac death or myocardial infarction. Inconclusive stress test was defined by echocardiography or nuclear stress testing with uncertain conclusion about the diagnosis of CAD. To characterize this population, an unsupervised clustering analysis was performed using 18 variables. Univariable and multivariable Cox regressions were performed to determine the prognostic value of inducible ischemia by stress CMR in each cluster. RESULTS Of 1502 patients with inconclusive stress test (62 ± 12 years, 59% men), 1441 (96%) completed the CMR protocol and 1397(93%) completed the follow-up (median 5.5 ± 2.3 years). Stress CMR was well tolerated without occurrence of death or severe adverse event. The clustering analysis identified 3 clusters: Cluster 1 (n = 524, 35%) had the highest prevalence of previous percutaneous coronary intervention (PCI), the highest presence of myocardial scar on CMR, the lowest LVEF(35 ± 7%) and the highest degree of LV dilatation. Cluster 2 (n = 406, 27%) had the highest prevalence of previous coronary artery bypass grafting (CABG), preserved LVEF(54 ± 10%), absence of LV dilatation and rate of male(89%). Cluster 3 (n = 572, 38%) had the lowest rate of previous PCI/CABG and of myocardial scar. This cluster gathered the oldest patients (73 ± 11 years), predominantly female (60%), with the highest rate of atrial fibrillation and body mass index. Survival analysis found significant differences across clusters for the occurrence of MACE (p = 0.02). Moreover, inducible ischemia was significantly associated with the occurrence of MACE in each cluster (cluster 1, HR 2.28; [95%CI: 1.31-3.99]; p = 0.0028; cluster 2, HR 3.37; [95%CI, 1.97-5.75]; p &amp;lt; 0.0001; cluster 3, HR 2.73; [95%CI, 1.67-4.46]; p &amp;lt; 0.0001). In multivariable Cox regression, inducible ischemia was an independent predictor of a higher incidence of MACE in each cluster (p &amp;lt; 0.001). CONCLUSIONS Cluster analysis identified 3 different phenotypes of patients with inconclusive stress test that were associated with distinct clinical and prognostic profiles. Within these clusters, CMR stress has an additional prognostic value to predict the occurrence of MACE. Abstract Figure. Kaplan-Meier for MACE in each cluster

Chest pain of unknown coronary origin: can exercise ECG testing contribute to long-term risk prediction on top of vasodilator stress cardiac magnetic resonance?

Abstract Background The prognostic value of both exercise ECG testing (ExECG) and vasodilator stress cardiac magnetic resonance (VS-CMR) is well-known in patients with chest pain of unknown coronary origin. However, it is unknown whether performing both techniques can improve the risk stratification of these patients. Purpose We aim to confirm the additive prognostic value of ExECG and VS-CMR in a real-world cohort of patients with chest pain of unknown coronary origin. Methods We retrospectively included 288 patients in which ExECG and VS-CMR had been subsequently performed within one year. Clinical, ExECG and VS-CMR variables were registered. We performed univariate and multivariate analysis to check for the association of variables with the risk of MACE, defined as a combined endpoint of acute coronary syndrome (ACS), admission for heart failure (aHF) or all-cause death. Results During a mean follow-up of 4.2±2.15 years, we registered 27 MACE (15 ACS, 8 aHF and 8 all-cause deaths). The history of hypertension, previous coronary artery disease and/or coronary artery bypass grafting, lower maximal heart rate during ExECG (maxHR) and more extensive ischemic burden (segments with perfusion defects -PD- on stress first-pass perfusion) and myocardial necrosis (number of segments with necrosis at late gadolinium enhancement imaging) associated with the MACE endpoint. However, the only independent predictors of MACE were maxHR during ExECG (HR 0.98 [0.96–0.99], p=0.01) and more extensive segments with PD in the VS-CMR (HR 1.2 [1.07–1.34], p=0.002). We identified the best cut-off using the Youden index derived from receiver operating characteristics (ROC) analysis to predict MACE - it was ≤130bpm for maxHR during ExECG and ≥2 segments with PD on VS-CMR. These cathegories allowed us to stratify the annualized rate of MACE, which was very low (0.97%/year) in patients with normal maxHR and no PD on VS-CMR, intermediate in patients with only abnormal maxHR (1.98%/year) or PD on VS-CMR (3.24%/year) and high in patients with both abnormal maxHR and segments with PD (6.26%/year). Adding maxHR to the multivariable model including stress-induced PD by VS-CMR significantly improved the predictive power of MACE as derived from the continuous reclassification improvement index (0.47 [0.10–0.81], p&amp;lt;0.05). Conclusions ExECG and VS-CMR can have an additive prognostic value to predict the long-term risk of MACE in patients with chest pain of unknown coronary origin. Patients with maxHR during ExECG ≤130bpm and ≥2 segments with PD on VS-CMR are at the highest risk of MACE. Figure 1. MACE risk stratification. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (PIE15/00013, PI17/01836, and CIBERCV16/11/00486 grants) and by Generalitat Valenciana (GV/2018/116).