Stress Cardiac Magnetic Resonance Research Articles

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.

Cold pressor testing and sympathetic nervous system contribution to ischemia with no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project

Study objectiveCold pressor testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. DesignProspective cohort. SettingAcademic hospital. Participants107 women with suspected INOCA and 21-age-matched reference women. InterventionsCPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n = 42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. Main outcome measureMPRIRPP. ResultsCompared to reference women, the INOCA group demonstrated higher resting RPP (p = 0.005) and CPT MPRIRPP (1.09 ± 0.36 vs 0.83 ± 0.18, p = 0.002). Furthermore, INOCA women with impaired ΔCBF (n = 23) had higher CPT MPRIRPP (p = 0.044) compared to reference women despite lower left ventricular ejection fraction (64 ± 7% vs 69 ± 2%, p = 0.005) and higher mass-to-volume ratio (0.79 ± 0.15 vs 0.62 ± 0.09, p < 0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. ConclusionsMyocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. This CPT response was also noted in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Therapies to modulate sympathetic activity should be studied in this population.

Preventing unnecessary imaging in patients suspect of coronary artery disease through machine learning of electronic health records.

With the ageing European population, the incidence of coronary artery disease (CAD) is expected to rise. This will likely result in an increased imaging use. Symptom recognition can be complicated, as symptoms caused by CAD can be atypical, particularly in women. Early CAD exclusion may help to optimize use of diagnostic resources and thus improve the sustainability of the healthcare system. To develop sex-stratified algorithms, trained on routinely available electronic health records (EHRs), raw electrocardiograms, and haematology data to exclude CAD in patients upfront. We trained XGBoost algorithms on data from patients from the Utrecht Patient-Oriented Database, who underwent coronary computed tomography angiography (CCTA), and/or stress cardiac magnetic resonance (CMR) imaging, or stress single-photon emission computerized tomography (SPECT) in the UMC Utrecht. Outcomes were extracted from radiology reports. We aimed to maximize negative predictive value (NPV) to minimize the false negative risk with acceptable specificity. Of 6808 CCTA patients (31% female), 1029 females (48%) and 1908 males (45%) had no diagnosis of CAD. Of 3053 CMR/SPECT patients (45% female), 650 females (47%) and 881 males (48%) had no diagnosis of CAD. On the train and test set, the CCTA models achieved NPVs and specificities of 0.95 and 0.19 (females) and 0.96 and 0.09 (males). The CMR/SPECT models achieved NPVs and specificities of 0.75 and 0.041 (females) and 0.92 and 0.026 (males). Coronary artery disease can be excluded from EHRs with high NPV. Our study demonstrates new possibilities to reduce unnecessary imaging in women and men suspected of CAD.

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.

Clinical values of resting electrocardiography in patients with known or suspected chronic coronary artery disease: a stress perfusion cardiac MRI study

BackgroundElectrocardiography (ECG) is an essential investigation in patients with chronic coronary artery disease (CAD). However, evidence regarding the diagnostic and prognostic value of ECG in this population is limited. Therefore, we sought to determine whether baseline ECG abnormalities were associated with myocardial ischemia and cardiac events in patients with known or suspected chronic CAD.MethodsConsecutive patients with known (n = 146) or suspected chronic CAD (n = 349) referred for adenosine stress cardiac magnetic resonance (CMR) between 2011 and 2014 were enrolled. Resting ECGs were classified as major, minor, and no abnormalities. Predictors of myocardial ischemia on CMR and major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, hospitalization for heart failure and late revascularization (> 180 days after CMR) were evaluated.ResultsAverage age was 69 ± 11 years (51% men). One hundred and eighty-five patients (37.4%) had major and 154 (31.1%) had minor ECG abnormalities. In patients with suspected CAD, myocardial ischemia was presented in 83 patients (23.8%). Multivariable analysis demonstrated major ECG abnormality as the strongest predictor of myocardial ischemia (HR 2.51; 95% CI 1.44–4.36; p = 0.001). Adding ECG to clinical pretest probability models improved the prediction of myocardial ischemia in ROC analyses (p = 0.04). In the whole cohort (n = 495), 91 MACE occurred during the median follow-up period of 4.8 years. Multivariable analysis showed that diabetes mellites, history of heart failure, prior revascularization, left ventricular ejection fraction, ischemia, and major ECG abnormality were independent predictors of MACE.ConclusionAbnormal resting ECG is common in patients with known or suspected chronic CAD. ECG had important diagnostic and prognostic values in this population.

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test.

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations.Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion.Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: −19.4 ± 1.9%, GLSDHE: −20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= −19.5 ± 2.3%, GLSDob= −19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001).Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive 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.

Fast-Strain Encoded Cardiac Magnetic Resonance During Vasodilator Perfusion Stress Testing.

Background: Cardiac magnetic resonance perfusion imaging during vasodilator stress is an established modality in patients with suspected and known coronary artery disease (CAD).Aim: This study aimed to evaluate the performance of fast-Strain-Encoded-MRI (fast-SENC) for the diagnostic classification and risk stratification of patients with ischemic heart disease.Methods: Perfusion and fast-SENC cardiac magnetic resonance (CMR) images were retrospectively analyzed in 111 patients who underwent stress CMR. The average myocardial perfusion score index, global and segmental longitudinal and circumferential strain (GLS and GCS and SLS and SCS, respectively), were measured at rest and during stress. The combination of SLS and SCS was referred to as segmental aggregate strain (SAS). Segments exhibiting perfusion defects or SAS impairment during stress were defined as “ischemic.” All-cause mortality, non-fatal infarction, and urgent revascularization were deemed as our combined clinical endpoint.Results: During adenosine stress testing, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. During a mean follow-up of 1.94 ± 0.65 years, 25 (22.5%) patients reached the combined endpoint (death in n = 2, infarction in n = 3 and urgent revascularization in n = 20). Inducible perfusion defects were associated with higher number of segments with inducible SAS reduction ≥6.5% (χ2 = 37.8, AUC = 0.79, 95% CI = 0.71–0.87, p < 0.001). In addition, patients with inducible perfusion defects or SAS impairment exhibited poorer outcomes (AUCPerf = 0.81 vs. AUCSAS = 0.74, p = NS vs. each other, and χ2 = 30.8, HR = 10.3 and χ2 = 9.5, HR = 3.5, respectively, p < 0.01 for both).Conclusion: Purely quantitative strain analysis by fast-SENC during vasodilator stress was related to the diagnosis of ischemia by first-pass perfusion and is non-inferior for the risk stratification of patients with ischemic heart disease. This may bear clinical implications, especially in patients with contraindications for contrast agent administration.

Pressure-volume relationship by pharmacological stress cardiovascular magnetic resonance.

The variation between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an index of myocardial contractility, easily obtained during routine stress echocardiography and never tested during dipyridamole stress-cardiac magnetic resonance (CMR). We assessed the ΔESPVR index in patients with known/suspected coronary artery disease (CAD) who underwent dipyridamole stress-CMR. One-hundred consecutive patients (24 females, 63.76 ± 10.17years) were considered. ESPVR index was evaluated at rest and stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson's method. The ΔESPVR index showed a good inter-operator reproducibility. Mean ΔESPVR index was 0.48 ± 1.45mmHg/mL/m2. ΔESPVR index was significantly lower in males than in females. ΔESPVR index was not correlated to rest left ventricular end-diastolic volume index or ejection fraction. Forty-six of 85 patients had myocardial fibrosis detected by the late gadolinium enhancement technique and they showed significantly lower ΔESPVR values. An abnormal stress CMR was found in 25 patients and they showed significantly lower ΔESPVR values. During a mean follow-up of 56.34 ± 30.04months, 24 cardiovascular events occurred. At receiver-operating characteristic curve analysis, a ΔESPVR < 0.02mmHg/mL/m2 predicted the presence of future cardiac events with a sensitivity of 0.79 and a specificity of 0.68. The noninvasive assessment of the ΔESPVR index during a dipyridamole stress-CMR exam is feasible and reproducible. The ΔESPVR index was independent from rest LV dimensions and function and can be used for a comparative assessment of patients with different diseases. ΔESPVR indexby CMR can be a useful and simple marker for additional prognostic stratification.

Abstract 12603: Impaired Coronary Flow Reserve in Athletes With Long-Term Cardiovascular Symptoms After COVID-19

Introduction: Cardiovascular symptoms post-acute sequelae of SARS-CoV-2 infection (CV-PASC) have been increasingly recognized, but the underlying pathobiology is unclear. Endothelial and cardiac pericyte ACE2 receptors are important targets of SARS-CoV-2, resulting in virally-induced endothelial activation, which may adversely affect the coronary microvasculature and impair myocardial performance. We hypothesized that athletes with CV-PASC have microvascular and subclinical myocardial dysfunction. Methods: We compared 15 athletes with CV-PASC with 7 control athletes without prior COVID-19 using regadenoson stress cardiac magnetic resonance (CMR). All athletes participated in &gt;6 hours of endurance activities per week. We analyzed CMR volumes, function, global circumferential strain (GCS), late gadolinium enhancement (LGE), and coronary flow reserve (CFR) by coronary sinus method. Values presented as median [IQR]. Results: CMR in CV-PASC athletes occurred 102 [66,123] days post-SARS-CoV-2 infection. There were no differences in chamber volumes, function, or LGE between groups. One CV-PASC athlete had acute myocarditis (7%). CV-PASC athletes had decreased CFR compared with control athletes ( Figure 1 ). Multiple CV-PASC participants had CFR below the 95% CI of the controls and reported normal values from the literature (2.9 and 2.5, respectively). GCS was worse in CV-PASC athletes at the base (-23.7% [-21.6,-26.4] vs -31.1% [-27.3,-33.0], p=0.01), mid-LV (-21.5% [-18.5,-22.8] vs -28.5 [-25.4,-29.9], p=0.008), and apex (-27.1% [-24.1,-29.9] vs -30.6% [-27.8,-38], p=0.07), though the apex did not reach statistical significance. Conclusions: This pilot case-control study found CV-PASC athletes had reduced CFR and associated subclinical myocardial dysfunction as assessed by GCS compared to control athletes. These findings suggest coronary microvascular dysfunction related to endothelial injury may mediate CV-PASC symptoms.

Histologic validation of stress cardiac magnetic resonance T1-mapping techniques for detection of coronary microvascular dysfunction in rabbits

BackgroundTo investigate the diagnostic performance of stress cardiac magnetic resonance (CMR) T1-mapping for the detection of coronary microvascular dysfunction (CMD) by correlating microvascular density (MVD) and collagen volume fraction (CVF) with T1 response to adenosine triphosphate (ATP) stress (stress ΔT1) in rabbits. MethodsTwenty-four New Zealand white rabbits were randomly divided into the CMD group induced by microembolization spheres (n = 10), sham-operated group (n = 5), and control group (n = 9). All rabbits underwent 3.0 T CMR, both rest and ATP stress T1-maps were obtained, and first-pass perfusion imaging was performed. Stress ΔT1 and myocardial perfusion reserve index (MPRI) were calculated. For the histologic study, each rabbit was sacrificed after CMR scanning. Left ventricular myocardial tissue was stained with Hematoxylin-eosin (H&E), Masson, and CD31, from which MVD and CVF were extracted. Pearson correlation analyses were performed to determine the strength of the association between the stress ΔT1 and both MVD and CVF. ResultsThe stress ΔT1 values (CMD, 2.53 ± 0.37% vs. control, 6.00 ± 0.64% vs. Sham, 6.07 ± 0.97%, p < 0.001) and MPRI (CMD, 1.45 ± 0.13 vs. control, 1.94 ± 0.23, vs. sham, 1.89 ± 0.15, p < 0.001) were both lower in CMD rabbits compared with sham-operated and control rabbits. Further, the stress ΔT1 showed a high correlation with CVF (r = −0.806, p < 0.001) and MVD (r = 0.920, p < 0.001). ConclusionsStress T1 response strongly correlates with pathological MVD and CVF, indicating that stress CMR T1 mapping can accurately detect microvascular dysfunction.

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.

Regadenoson stress CMR: safety, feasibility and hemodynamic response

Abstract Background and objectives The use of regadenoson for stress cardiac magnetic resonance (CMR) has potential advantages over other vasodilators. We sought to evaluate the safety, feasibility and hemodynamic response (heart rate and blood pressure) of regadenoson in an unselected population undergoing stress CMR for clinical work-up. Methods A total of 603 regadenoson stress CMR clinical examinations performed between May 2017 and May 2020 in our institution were retrospectively reviewed. Studies were performed using a conventional stress/rest CMR protocol with a 1.5T MRI scanner. A fixed dose of 5 ml of regadenoson was employed as stressor. As part of the protocol, 200 mg of theophylline was administered between stress and rest acquisitions to reverse the vasodilator effect of regadenoson. Adverse events, clinical symptoms, and hemodynamic response were assessed. Results In our cohort, no severe adverse events requiring hospitalization were observed, and only 5 adverse events were reported (0.83%). Only two patients (0.3%) did not complete the test due to adverse events or symptoms related to regadenoson administration (one case presented severe hypotension; the other presented unbearable chest pain). There were no cases of bronchospasm, stress-induced arrhythmia or death. Over half of patients reported mild symptoms after drug administration (52%, n=314), more frequently dyspnea (19%, n=112), chest pain (18%, n=106) and flushing (6%, n=34). All symptoms resolved after theophylline administration. Overall, an increase in heart rate (mean increase and (standard deviation) = 24 (12.6) bpm and a mild decrease in systolic (−8.2 (17.1) mmHg) and diastolic (−4.9 (10.2) mmHg) blood pressure were observed as response to regadenoson. A blunted heart rate response was observed in elderly (p&amp;lt;0.01), diabetic (p&amp;lt;0.01) and obese (p=0.01) patients. Only 46 patients (7.8%) did not show tachycardization response. Conclusions The use of regadenoson in stress CMR proved to be safe and feasible in the vast majority of patients. Adverse events were not frequent with regadenoson and symptoms were transient and well tolerated, while premature ending of the test related to drug administration was very rare. Funding Acknowledgement Type of funding sources: None. Hemodynamic response

PERAN PEMERIKSAAN NON INVASIF DAN PENCITRAAN KARDIOVASKULAR DALAM MANAJEMEN PENYAKIT JANTUNG KORONER

&lt;p&gt;&lt;em&gt;Noninvasive cardiac test is a cornerstone of the diagnostic work-up in patients with suspected coronary artery disease (CAD). It is essential for the assessment of CAD and considered the gate-keeper to invasive coronary angiography. Cardiac tests include exercise electrocardiography, single photon emission computed tomography myocardial perfusion imaging, positron emission tomography myocardial perfusion imaging, stress echocardiography, coronary computed tomography angiography, and stress cardiac magnetic resonance. However, clinicians face a challenge when deciding which test is most appropriate for a given patient. Basic knowledge of each modality will facilitate the decision-making process in CAD assessment&lt;/em&gt;&lt;em&gt;.&lt;/em&gt;&lt;/p&gt;

Human hyperpolarized [1-13C] pyruvate CMR and adenosine stress test

Abstract Background Hyperpolarized (HP) [1-13C]pyruvate cardiac magnetic resonance (CMR) imaging can visualize myocardial perfusion and metabolism beyound glucose uptake. Depending on the prevailing metabolic conditions, buid-up of either [1-13C]lactate or 13C-bicarbonate can be measured. The aim of the present study was to assess cardiac metabolism using HP [1-13C]pyruvate rest-stress CMR. Methods Six healthy volunteers underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during an adenosine stress test. Signal from HP [1-13C]pyruvate and its downstream metabolites was measured at the mid-left-ventricle (LV) level. We did semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion. Pressure-volume loops were assessed non-invasively. Results Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2±2.8 sec to 2.7±1.3 sec, p=0.04. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 0.011±0.009 sec–1 to 0.020±0.010 sec–1, p=0.04. The pyruvate oxidation (kPB) increased from 0.004±0.004 sec–1 to 0.012±0.007 sec–1, p=0.008. This increase in oxidative metabolism was positively correlated with heart rate (R2=0.44, p=0.02). Conclusion We observed a significant increase in carbohydrate oxidation during cardiac stress in the healthy human heart. The present study forms the basis for comparisons in future research in patients with heart failure and coronary artery disease. HP [1-13C]pyruvate CMR could be a possible alternative to PET in the future. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Danish Heart FoundationIndependent Research Fund, Denmark Increased conversion rate of pyruvateIncreased metabolite signal in LV

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

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.

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.