Stress Cardiovascular Magnetic Resonance Research Articles

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

The epidemiological characteristics and prognostic profiles of the population with CAD newly diagnosed are heterogeneous, particularly in terms of age, risk factors, degree of CAD burden and left ventricular abnormalities. To identify patient subgroups by phenotypic unsupervised clustering integrating clinical data, CCTA and CMR parameters to unveil pathophysiological differences between subgroups of patients with CAD newly diagnosed. Between 2008 and 2020, consecutive symptomatic patients without known CAD referred for CCTA were screened. Among those, patients with obstructive CAD (at least 1 ≥ 50% stenosis on CCTA) and referred for stress CMR were included and followed for MACE (CV death or nonfatal MI). A cluster analysis was performed on clinical, CCTA and CMR variables. In total, 2015 patients (46.3% male, mean age 70 ± 12 years) completed the follow-up (median: 6.8 [IQR: 5.9–9.2] years). Three mutually exclusive phenogroups (PG) were identified: [PG1] older females without CV risk factor, without proximal stenosis by CCTA and preserved LVEF; [PG2] young females with several CV risk factors, with calcified stenosis by CCTA and preserved LVEF; and [PG3] young males with ≥ 1 proximal significant stenosis without calcification by CCTA, myocardial scar and reduced LVEF. The occurrence of MACE ( P < 0.001), cardiovascular mortality ( P < 0.001) and all-cause mortality ( P < 0.001) differed among the three phenogroups. The PG3 presented the worse prognosis. In each phenogroup, 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 < 0.001) ( Fig. 1 ). Cluster analysis of clinical, CCTA and CMR variables identified 3 phenogroups of patients with CAD newly diagnosed 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.

Feasibility of adenosine stress cardiovascular magnetic resonance perfusion imaging in patients with MR-conditional transvenous permanent pacemakers and defibrillators

BackgroundThe use of stress perfusion-cardiovascular magnetic resonance (CMR) imaging remains limited in patients with implantable devices. The primary goal of the study was to assess the safety, image quality, and the diagnostic value of stress perfusion-CMR in patients with MR-conditional transvenous permanent pacemakers (PPM) or implantable cardioverter-defibrillators (ICD).MethodsConsecutive patients with a transvenous PPM or ICD referred for adenosine stress-CMR were enrolled in this single-center longitudinal study. The CMR protocol was performed using a 1.5 T system according to current guidelines while all devices were put in MR-mode. Quality of cine, late-gadolinium-enhancement (LGE), and stress perfusion sequences were assessed. An ischemia burden of ≥ 1.5 segments was considered significant. We assessed the safety, image quality and the occurrence of interference of the magnetic field with the implantable device. In case of ischemia, we also assessed the correlation with the presence of significant coronary lesions on coronary angiography.ResultsAmong 3743 perfusion-CMR examinations, 66 patients had implantable devices (1.7%). Image quality proved diagnostic in 98% of cases. No device damage or malfunction was reported immediately and at 1 year. Fifty patients were continuously paced during CMR. Heart rate and systolic blood pressure remained unchanged during adenosine stress, while diastolic blood pressure decreased (p = 0.007). Six patients (9%) had an ischemia-positive stress CMR and significant coronary stenoses were confirmed by coronary angiography in all cases.ConclusionStress perfusion-CMR is safe, allows reliable ischemia detection, and provides good diagnostic value.

Deep learning applications in myocardial perfusion imaging, a systematic review and meta-analysis

BackgroundCoronary artery disease (CAD) is a leading cause of death worldwide, and the diagnostic process comprises of invasive testing with coronary angiography and non-invasive imaging, in addition to history, clinical examination, and electrocardiography (ECG). A highly accurate assessment of CAD lies in perfusion imaging which is performed by myocardial perfusion scintigraphy (MPS) and magnetic resonance imaging (stress CMR). Recently deep learning has been increasingly applied on perfusion imaging for better understanding of the diagnosis, safety, and outcome of CAD.The aim of this review is to summarise the evidence behind deep learning applications in myocardial perfusion imaging. MethodsA systematic search was performed on MEDLINE and EMBASE databases, from database inception until September 29, 2020. This included all clinical studies focusing on deep learning applications and myocardial perfusion imaging, and excluded competition conference papers, simulation and animal studies, and studies which used perfusion imaging as a variable with different focus. This was followed by review of abstracts and full texts. A meta-analysis was performed on a subgroup of studies which looked at perfusion images classification. A summary receiver-operating curve (SROC) was used to compare the performance of different models, and area under the curve (AUC) was reported. Effect size, risk of bias and heterogeneity were tested. Results46 studies in total were identified, the majority were MPS studies (76%). The most common neural network was convolutional neural network (CNN) (41%). 13 studies (28%) looked at perfusion imaging classification using MPS, the pooled diagnostic accuracy showed AUC = 0.859. The summary receiver operating curve (SROC) comparison showed superior performance of CNN (AUC = 0.894) compared to MLP (AUC = 0.848). The funnel plot was asymmetrical, and the effect size was significantly different with p value < 0.001, indicating small studies effect and possible publication bias. There was no significant heterogeneity amongst studies according to Q test (p = 0.2184). ConclusionDeep learning has shown promise to improve myocardial perfusion imaging diagnostic accuracy, prediction of patients’ events and safety. More research is required in clinical applications, to achieve better care for patients with known or suspected CAD.

Prognostic value of stress CMR-related coronary revascularization to predict death: A propensity score matching analysis a large registry with &gt; 200,000 patient-years of follow-up

While the benefit of coronary revascularization in patients with stable CAD is debated, data assessing the potential interest of stress CMR to guide coronary revascularization are limited. To assess the long-term prognostic value of stress CMR-related coronary revascularization in consecutive patients from a large registry. Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 years (IQR: 5.0–8.0) included all consecutive patients referred for stress CMR. Stress CMR-related coronary revascularization was defined by any coronary revascularization performed within 90 days after CMR with presence of inducible ischemia. The primary outcome was all-cause death based on the National Death Registry. Among the 31,752 consecutive patients (mean age 63.7 ± 12.1 years and 65.7% males), 2679 (8.4%) died at 206,453 patient-years of follow-up. In the overall population, CMR-related coronary revascularization was an independent predictor of greater survival (HR: 0.58; 99.5% CI: 0.46–0.74; P < 0.001). In 1680, 1:1 matched patients using a limited number of variables (840 revascularized, 840 non-revascularized), CMR-related revascularization was associated with a lower incidence of death only in patients with severe inducible ischemia (> 5 segments, P < 0.001), but showed no benefit in patients with mild or moderate ischemia (≤ 5 segments, P = 0.109). Using multivariable analysis in the propensity-matched population, CMR-related revascularization remained an independent predictor of a lower incidence of all-cause mortality (HR = 0.66; 99.5% CI: 0.54–0.80, P < 0.001) ( Fig. 1 ). In this large observational series of consecutive patients, stress CMR-related revascularization guided by the presence of inducible ischemia was associated with a lower incidence of death in patients with severe ischemia.

Incremental long-term prognostic value of stress CMR above traditional risk factors to predict death a large registry with &gt; 200,000 patient-years of follow-up

While the benefit of coronary revascularization in patients with stable coronary artery disease (CAD) is debated, data assessing the potential interest of stress CMR to guide coronary revascularization are limited. To assess the long-term prognostic value of stress CMR in consecutive patients from a large registry. Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 years (IQR: 5.0–8.0) included all consecutive patients referred for stress CMR. The primary outcome was all-cause death based on the National Death Registry. Among the 31,752 consecutive patients (mean age 63.7 ± 12.1 years and 65.7% males), 2679 (8.4%) died at 206,453 patient-years of follow-up. Inducible ischemia and late gadolinium enhancement (LGE) by CMR were associated with death (both P < 0.001). In multivariable Cox regression, inducible ischemia and LGE were independent predictors of death (HR = 1.61; 99.5% CI: 1.41–1.84; HR = 1.62; 99.5% CI: 1.41–1.86, respectively; P < 0.001). The addition of LVEF, LGE and inducible ischemia significantly improved the C statistic to 0.71 (99.5% CI: 0.70–0.72; C statistic improvement for model 1: 0.03; NRI = 0.035). The addition of the presence of LGE and the number of segments of LGE and inducible ischemia significantly improved the C statistic to 0.74 (99.5% CI: 0.73–0.75; C statistic improvement for model 1: 0.06; NRI = 0.061) ( Fig. 1 ). In this large observational series of consecutive patients, stress perfusion CMR had important incremental long-term prognostic value to predict death over traditional risk factors.

High-resolution non-contrast free-breathing coronary cardiovascular\xa0magnetic resonance angiography for detection of coronary artery disease: validation against invasive coronary angiography

BackgroundCoronary artery disease (CAD) is the single most common cause of death worldwide. Recent technological developments with coronary cardiovascular magnetic resonance angiography (CCMRA) allow high-resolution free-breathing imaging of the coronary arteries at submillimeter resolution without contrast in a predictable scan time of ~ 10 min. The objective of this study was to determine the diagnostic accuracy of high-resolution CCMRA for CAD detection against the gold standard of invasive coronary angiography (ICA).MethodsForty-five patients (15 female, 62 ± 10 years) with suspected CAD underwent sub-millimeter-resolution (0.6 mm3) non-contrast CCMRA at 1.5T in this prospective clinical study from 2019–2020. Prior to CCMR, patients were given an intravenous beta blockers to optimize heart rate control and sublingual glyceryl trinitrate to promote coronary vasodilation. Obstructive CAD was defined by lesions with ≥ 50% stenosis by quantitative coronary angiography on ICA.ResultsThe mean duration of image acquisition was 10.4 ± 2.1 min. On a per patient analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 95% (75–100), 54% (36–71), 60% (42–75) and 93% (70–100), respectively. On a per vessel analysis the sensitivity, specificity, positive predictive value and negative predictive value (95% confidence intervals) were 80% (63–91), 83% (77–88), 49% (36–63) and 95% (90–98), respectively.ConclusionAs an important step towards clinical translation, we demonstrated a good diagnostic accuracy for CAD detection using high-resolution CCMRA, with high sensitivity and negative predictive value. The positive predictive value is moderate, and combination with CMR stress perfusion may improve the diagnostic accuracy. Future multicenter evaluation is now required.

401 Myocardial viability and ischaemia assessment in chronic coronary total occlusions according to collaterals distribution: a retrospective analysis

Abstract Aims Whether CTO-PCI (chronic total occlusions—percutaneous coronary intervention) offers clinical benefit over optimal medical therapy is still a matter of debate. Viability and ischaemia assessment could improve selection of candidates to PCI. Traditionally, well-developed collaterals are considered a marker of myocardial viability in CTO territory. Current literature offers few data concerning the relationship between viability/ischaemia and collaterals distribution. Methods and results We retrospectively analysed the Cardiovascular Magnetic Resonance (CMR) studies and coronary angiographies of patients with at least one CTO referred at Humanitas Research Hospital between June 2009 and September 2020. We included 131 patients who underwent CMR with LGE assessment; of them, 111 (85%) underwent stress-CMR with adenosine. AHA segments (16 segment/patient for a total of 2096 segment assessed) were assessed on three short axis projection and scored for WMSI on cine images, for the presence of ischaemia on first pass perfusion, and for viability on LGE images. Viability was defined as LGE transmurality ≤50% and WMSI (wall motion score index) &amp;gt;1. Patients were divided in three groups according to collaterals distribution at coronary angiography: Patients with TD collaterals were more likely to have viable segments in the CTO-territory (90% of the segments in TD, 76% in WD, and 71% in PD, coeff. 0.107, P &amp;lt; 0.001). No statistically significant differences were found between groups as regard the amount of ischaemic segments (61% of the segments in TD, 65% in WD, and 60% in PD, P = 0.189). Conclusions The presence of myocardial viability is slightly associated with the degree of coronary collateralization at coronary angiography while the amount of ischaemia is not. Stress CMR should be considered in CTO patients before a reopening attempt.

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 11227: Ischemia Mediated Contractile Dysfunction Modulates Functional Mitral Regurgitation - Multiparametric Strain and Tissue Characterization Data from the Society of Cardiovascular Magnetic Resonance (scmr) Registry

Introduction: LV ischemia has been linked to functional mitral regurgitation (FMR) but ischemia is present many pts without FMR. CMR concomitantly assesses MR, ischemia and LV function but has not been used to test factors modifying impact of ischemia on FMR. Methods: Vasodilator stress CMR was performed in CAD pts in a multicenter registry, in whom advanced (≥moderate) FMR was confirmed by core lab. LV ischemia was categorized by subpapillary involvement (subtending mitral apparatus). To test mechanism by which ischemia impacts FMR, LV strain was measured in pts with ischemia and &lt;5% LV infarct, with and without (1:2) FMR, matched for ischemia extent/distribution. Followup was done for mortality. Results: 2639 pts were studied; 7% had advanced FMR. While FMR pts had more ischemia in subpapillary (21.8 ± 28.3 vs 13.4 ± 21.9%) and nonpapillary (19.2 ± 25.5 vs 13.0 ± 22.2%) regions (p&lt;0.001), multivariate analysis showed only subpapillary ischemia (OR 1.13 per 5% LV [1.05, 1.21] p=0.001) to be associated with FMR (nonpapillary p=NS). Wall motion scores in ischemic subpapillary segments were higher in pts with FMR (1.7±0.9 vs 0.8±0.9, p&lt;0.001) paralleling strain subgroup data (n=114): FMR prevalence increased stepwise with impaired radial and circumferential strain ( Figure ). Adverse mitral remodeling associated with impaired strain; mitral tenting area (OR -0.01 per % [-0.02, -0.004] p&lt;0.01) and papillary fractional shortening (OR 0.36 per % [0.26, 0.47] p&lt;0.001) each associated with subpapillary radial strain controlling for nonpapillary strain (p=NS). On follow up (median 4.7 [2.2, 7.7] yr), FMR, age, subpapillary ischemia and infarction each independently predicted death (p&lt;0.001): When categorized as dysfunctional or non-dysfunctional, only ischemic/dysfunctional myocardium (HR 1.15 per 5% LV [1.05, 1.14] p&lt;0.001) associated with death. Conclusions: Ischemia mediated LV dysfunction on multiparametric CMR modulates likelihood of FMR and adverse prognosis.

Prognostic value of pre-hospitalization stress perfusion cardiovascular magnetic resonance to predict death in patients hospitalized for COVID-19

BackgroundInducible ischaemia is a strong marker of vascular vulnerability. Knowing the important role of the vascular tropism of COVID-19 to explain its severity, the presence of a prior inducible ischaemia may be a key pathogenetic determinant of COVID-19 severity.AimsTo investigate the prognostic value of prior inducible ischaemia on stress cardiovascular magnetic resonance (CMR) to predict death in patients hospitalized for COVID-19.MethodsWe retrospectively analysed consecutive patients referred for stress perfusion CMR during 1/1/18–1/1/20 who were later hospitalized for COVID-19. The primary outcome was all-cause death, including in-hospital and post-hospitalization deaths, based on the electronic national death registry.ResultsAmong the patients referred for stress CMR, 481 were hospitalized for COVID-19 (mean age 68.4 ± 9.6 years, 61.3% male) and completed the follow-up (median [interquartile range] 73 [36–101] days). There were 93 (19.3%) all-cause deaths, of which 13.7% occurred in hospital and 5.6% were post-hospitalization deaths. Age, male sex, hypertension, diabetes, known coronary artery disease (CAD), the presence of prior inducible ischaemia, the number of ischaemic segments, the presence of late gadolinium enhancement and left ventricular ejection fraction were significantly associated with all-cause death. In multivariable stepwise Cox regression analysis, age (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01–1.07; P = 0.023), hypertension (HR: 2.77; 95% CI: 1.71–4.51; P < 0.001), diabetes (HR: 1.72; 95% CI: 1.08–2.74; P = 0.022), known CAD (HR: 1.78; 95% CI: 1.07–2.94; P = 0.025) and prior inducible ischaemia (HR 2.05; 95% CI: 1.27–3.33; P = 0.004) were independent predictors of all-cause death.ConclusionsIn COVID-19 patients, prior inducible ischaemia by stress CMR during the 2 years preceding the COVID-19 pandemic was independently associated with all-cause death.

Combined assessment of stress cardiovascular magnetic resonance and angiography to predict the effect of revascularization in chronic coronary syndrome patients.

The role of revascularization in chronic coronary syndrome (CCS) and the value of ischaemia vs. anatomy to guide decision-making are in constant debate. We explored the potential of a combined assessment of ischaemic burden by vasodilator stress cardiovascular magnetic resonance (CMR) and presence of multivessel disease by angiography to predict the effect of revascularization on all-cause mortality in CCS. The study group comprised 1066 CCS patients submitted to vasodilator stress CMR pre-cardiac catheterization (mean age 66 ± 11 years, 69% male). Stress CMR-derived ischaemic burden (extensive if >5 ischaemic segments) and presence of multivessel disease in angiography (two- or three-vessel or left main stem disease) were computed. The influence of revascularization on all-cause mortality was explored and adjusted hazard ratios (HRs) with the corresponding 95% confidence intervals were obtained. During a median 7.51-year follow-up, 557 (52%) CMR-related revascularizations and 308 (29%) deaths were documented. Revascularization exerted a neutral effect on all-cause mortality in the whole study group [HR 0.94 (0.74-1.19), P = 0.6], in patients without multivessel disease [n = 598, 56%, HR 1.12 (0.77-1.62), P = 0.6], and in those with multivessel disease without extensive ischaemic burden [n = 181, 17%, HR 1.66 (0.91-3.04), P = 0.1]. However, compared to non-revascularized patients, revascularization significantly reduced all-cause mortality in patients with simultaneous multivessel disease and extensive ischaemic burden (n = 287, 27%): 3.77 vs. 7.37 deaths per 100 person-years, HR 0.60 (0.40-0.90), P = 0.01. In patients with CCS submitted to catheterization, evidence of simultaneous extensive CMR-related ischaemic burden and multivessel disease identifies the subset in whom revascularization can reduce all-cause mortality.

Sex differences in mortality in stable patients undergoing vasodilator stress cardiovascular magnetic resonance

Abstract Introduction The prognostic value and therapeutic implications of ischemia as derived from vasodilator stress cardiovascular magnetic resonance (CMR) could differ in men and women, but it has not been stablished. Purpose We assessed the influence of the ischemic burden as derived from CMR on the risk of death and the effect of revascularization across sex. Methods We evaluated 6,237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischemia was defined as &amp;gt;5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used. Results A total of 2,371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularization. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived ischemic burden across sex (p-value for interaction=0.039). Women exhibited an adjusted lower risk of death along most of the continuous ischemic burden but equalled men's risk when extensive ischemia was present. Likewise, CMR-related revascularization was shown to be differentially associated with the risk of mortality across sex (p-value for interaction=0.025). In patients with non-extensive ischemia, revascularization was related to a higher risk of death, with a greater extent in women. At higher ischemic burden, revascularization was associated with a lower risk in men, with more uncertain results in women. Conclusions CMR-derived ischemic burden allows predicting the risk of death and gives insight into the potential effect of revascularization in men and women with CCS. Compared to men, women with nonextensive ischemia displayed a lower risk and a similar risk with a higher ischemic burden. The impact of CMR-related revascularization on mortality risk was also significantly different according to ischemic burden and sex. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Instituto de Salud Carlos III and cofunded by the European Regional Development Fund (ERDF).

Cardiac magnetic resonance strain and mechanical dispersion assessment in patients with chronic total coronary artery occlusion

Abstract Background Chronic total occlusions (CTO) are a frequent angiographic finding. Viability of CTO-subtended myocardium is dependent on the presence of an adequate collateral circulation. At rest, collateral supply may be sufficient to avert ischaemia and maintain normal systolic function. However, it remains unclear whether CTO-subtended myocardium may be considered truly normal, or whether subtle functional abnormalities may be present at rest. Purpose To determine whether, in the absence of infarction and hibernation, CTO-subtended myocardium remains functionally normal or whether abnormalities of strain and/or mechanical dispersion may be present at rest. Methods In a retrospective, single centre, observational study, we studied patients with ≥1 angiographically-diagnosed CTO referred for clinical stress perfusion cardiovascular magnetic resonance (CMR), and compared healthy volunteers (HVs) with a normal stress CMR scan. CMR imaging comprised functional and scar assessment with qualitative [visual] evaluation of infarction and segmental wall motion. Patients with infarction and/or wall motion score index (WMSI) ≥1 were excluded from further analysis. In remaining CTO subjects and HVs, segmental peak systolic longitudinal strain and circumferential strain were analysed (in 3 long-axis planes and 3 short-axis planes, respectively) and mechanical dispersion for both orientations was computed. Image analysis was performed using Medis (QStrain) software blinded to all clinical information. Results From a total of 389 patients with ≥1 angiographically-diagnosed CTO, 68 had normal WMSI and no infarction (63.0±11.7 years, 79.4% male, LVEF 62.6±4.5%). Fifty HVs (61.1±7.0 years, 74.0% males, LVEF 61.1±5.3%) were also studied. The majority of CTO patients had concomitant coronary artery disease in at least one non-CTO vessel (n=37, 54.4%). GLS was lower in CTO patients than HVs (−21.8%±1.5% versus −24.0±1.1%; p&amp;lt;0.0001; Figure 1). By contrast, GCS was greater in CTO patients (−32.7±2.5% versus −28.8±2.1%; p&amp;lt;0.0001). Mechanical dispersion was increased in CTO patients (Figure 2), both longitudinally (90.3±14.6 ms in CTO patients versus 68.6±11.1 ms in HVs; p&amp;lt;0.0001) and circumferentially (66.7±9.1 ms versus 55.3±6.6 ms, respectively; p=0.02). Conclusion Subclinical changes in left ventricular dynamics are present at rest in CTO patients with fully viable myocardium and no evidence of resting regional wall abnormality. Further study is warranted to evaluate the potential association between mechanical dispersion and arrhythmic events in CTO. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): NIHR Clinician Scientist Award (CS-2018-18-ST2-007 to J.R.A.) and Research Professorship award (RP-2017-08-ST2-007 to G.P.M.). Figure 1. Strain analysis. CTO vs HVFigure 2. Mechanical dispersion. CTO vs HV

The impact of dark-blood versus conventional bright-blood late gadolinium enhancement on the myocardial ischemic burden

PurposeIn perfusion cardiovascular magnetic resonance (CMR), ischemic burden predicts adverse prognosis and is often used to guide revascularization. Ischemic scar tissue can cause stress perfusion defects that do not represent myocardial ischemia. Dark-blood late gadolinium enhancement (LGE) methods detect more scar than conventional bright-blood LGE, however, the impact on the myocardial ischemic burden estimation is unknown and evaluated in this study. MethodsForty patients with CMR stress perfusion defects and ischemic scar on both dark-blood and bright-blood LGE were included. For dark-blood LGE, phase sensitive inversion recovery imaging with left ventricular blood pool nulling was used. Ischemic scar burden was quantified for both methods using >5 standard deviations above remote myocardium. Perfusion defects were manually contoured, and the myocardial ischemic burden was calculated by subtracting the ischemic scar burden from the perfusion defect burden. ResultsIschemic scar burden by dark-blood LGE was higher than bright-blood LGE (13.3 ± 7.4% vs. 10.3 ± 7.1%, p < 0.001). Dark-blood LGE derived myocardial ischemic burden was lower compared with bright-blood LGE (15.6% (IQR: 10.3 to 22.0) vs. 19.3 (10.9 to 25.5), median difference −2.0%, p < 0.001) with a mean bias of −2.8% (95% confidence intervals: −4.0 to −1.6%) and a large effect size (r = 0.62). ConclusionStress perfusion defects are associated with higher ischemic scar burden using dark-blood LGE compared with bright-blood LGE, which leads to a lower estimation of the myocardial ischemic burden. The prognostic value of using a dark-blood LGE derived ischemic burden to guide revascularization is unknown and warrants further investigation.

Long-Term Prognostic Value of Stress Cardiovascular Magnetic Resonance-Related Coronary Revascularization to Predict Death: A Large Registry With >200 000 Patient-Years of Follow-Up.

Although the benefit of coronary revascularization in patients with stable coronary disease is debated, data assessing the potential interest of stress cardiovascular magnetic resonance (CMR) to guide coronary revascularization are limited. We aimed to assess the long-term prognostic value of stress CMR-related coronary revascularization in consecutive patients from a large registry. Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 years (interquartile range, 5.0-8.0) included all consecutive patients referred for stress CMR. CMR-related coronary revascularization was defined by any coronary revascularization performed within 90 days after CMR. The primary outcome was all-cause death based on the National Death Registry. Among the 31 762 consecutive patients (mean age 63.7±12.1 years and 65.7% males), 2679 (8.4%) died at 206 453 patient-years of follow-up. Inducible ischemia and late gadolinium enhancement by CMR were associated with death (both P<0.001). In multivariable Cox regression, inducible ischemia and late gadolinium enhancement were independent predictors of death (hazard ratio, 1.61 [99.5% CI, 1.41-1.84]; hazard ratio, 1.62 [99.5% CI, 1.41-1.86], respectively; P<0.001). In the overall population, CMR-related coronary revascularization was an independent predictor of greater survival (hazard ratio, 0.58 [99.5% CI, 0.46-0.74]; P<0.001). In 1680, 1:1 matched patients using a limited number of variables (840 revascularized, 840 nonrevascularized), CMR-related revascularization was associated with a lower incidence of death in patients with severe inducible ischemia (≥6 segments, P<0.001) but showed no benefit in patients with mild or moderate ischemia (<6 segments, P=0.109). Using multivariable analysis in the propensity-matched population, CMR-related revascularization remained an independent predictor of a lower incidence of all-cause mortality (hazard ratio, 0.66 [99.5% CI, 0.54-0.80], P<0.001). In this large observational series of consecutive patients, stress perfusion CMR had important incremental long-term prognostic value to predict death over traditional risk factors. CMR-related revascularization was associated with a lower incidence of death in patients with severe ischemia.

Long-term prognostic value of ischaemia and cardiovascular magnetic resonance-related revascularization for stable coronary disease, irrespective of patient’s sex: a large retrospective study

To assess the sex-specific, long-term prognostic value of myocardial ischaemia induced by stress cardiovascular magnetic resonance (CMR) and early CMR-related revascularization in consecutive patients from a large registry. Between 2008 and 2010, all consecutive patients referred for stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular mortality or recurrent non-fatal myocardial infarction (MI). Early CMR-related revascularization was defined as any revascularization within 90 days after CMR. Among 3664 patients (56.9% male, mean age 69.9 ± 11.8 years), 472 (12.9%) had MACE (163 women and 309 men) after a median follow-up of 8.8 (IQR 6.9-9.5) years. Inducible ischaemia and late gadolinium enhancement (LGE) by CMR were associated with MACE in women and men (all P < 0.001). In multivariable Cox regression, inducible ischaemia, LGE, and CMR-related revascularization were independent predictors of MACE both in women [heart rate (HR) 4.79, 95% confidence interval (CI) 2.17-9.10; HR 1.82, 95% CI 1.22-2.71; HR 0.71, 95% CI 0.54-0.92, respectively; all P < 0.001] and men (HR 3.88, 95% CI 2.33-5.98; HR 1.48, 95% CI 1.16-1.89; HR 0.78, 95% CI 0.65-0.97, respectively; all P < 0.001). The addition of CMR-parameters led to improved model discrimination for MACE (C-statistic 0.61 vs. 0.71; NRI = 0.212; IDI = 0.032) for both women and men. CMR-related revascularization was associated with a lower incidence of MACE in patients with left ventricular ejection fraction (LVEF)<50%. Inducible ischaemia and early CMR-related revascularization were good long-term predictors of MACE irrespective of sex. CMR-related revascularization was associated with a lower MACE incidence in the sole sub-set of patients with LVEF < 50%.

Coronary artery spasm and impaired myocardial perfusion in patients with ANOCA: Predictors from a multimodality study using stress CMR and acetylcholine testing

BackgroundFunctional coronary disorders such as coronary spasm and microvascular dysfunction (including microvascular spasm and impaired microvascular dilatation) are frequent findings among patients with angina and non-obstructed coronary arteries (ANOCA). In this study, we investigated a potential association of coronary spasm and myocardial perfusion abnormalities as well as predictors of such functional coronary disorders in ANOCA patients using a multimodality diagnostic strategy including adenosine stress CMR and intracoronary acetylcholine testing. MethodsWe enrolled 129 patients with ANOCA who underwent acetylcholine testing and adenosine stress perfusion CMR. Patients were allocated to 3 groups according to their spasm testing result with regard to standardized COVADIS criteria: 1) epicardial spasm, 2) microvascular spasm, and 3) no spasm. The myocardial perfusion reserve index (MPRI) was semiquantitatively determined from adenosine stress perfusion CMR. Multivariate regression analyses were performed to identify predictors of coronary functional disorders. ResultsPatients with epicardial spasm had lower MPRI than patients without, whereas MPRI was preserved in patients with microvascular spasm. Multivariate analyses revealed age, previous myocardial infarction, LVEF and epicardial spasm as independent predictors of diminished MPRI, whereas previous PCI was associated with epicardial spasm, and female sex was a strong predictor of microvascular spasm. ConclusionsOur results demonstrate coexistence of different functional coronary disorder endotypes involving the macro- and microvascular level of the coronary circulation in patients with ANOCA. We demonstrate that epicardial spasm is associated with diminished myocardial perfusion reserve and report further predictors of coronary functional disorders.

Long-Term Prognostic Value of Stress CMR in Patients With Heart Failure and Preserved Ejection Fraction

ObjectivesThe objectives of this study were to investigate the long-term prognostic value of inducible myocardial ischemia assessed by vasodilator stress cardiovascular magnetic resonance (CMR) in patients with HFpEF. BackgroundSome studies suggest that ischemia could play a key role in HF in patients with preserved ejection fraction (HFpEF). MethodsBetween 2008 and 2019, consecutive patients prospectively referred for stress CMR with HFpEF as defined by current guidelines, without known coronary artery disease (CAD), were followed for the occurrence of major adverse cardiovascular events (MACE), as defined by cardiovascular mortality or nonfatal myocardial infarction (MI). Secondary composite outcomes included cardiovascular mortality or hospitalization for acute HF. Cox regression analysis was performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR. ResultsAmong the 1,203 patients with HFpEF (73 ± 13 years of age; 29% males) who underwent stress CMR and completed follow-up (6.9 years interquartile range [IQR]: 6.7 to 7.7 years]), 108 experienced a MACE (9%). Kaplan-Meier analysis showed inducible ischemia and LGE were significantly associated with MACE (HR: 6.63; 95% confidence interval [CI]: 4.54 to 9.69; and HR: 2.56; 95% CI: 1.60 to 4.09, respectively; both p < 0.001) and secondary outcomes (HR: 8.40; 95% CI: 6.31 to 11.20; p < 0.001; and HR: 1.87; 95% CI: 1.27 to 2.76, respectively; p = 0.002). In multivariate analysis, inducible ischemia and LGE were independent predictors of MACE (HR: 6.10; 95% CI: 4.14 to 9.00; p < 0.001 and HR: 1.62; 95% CI: 1.06 to 2.49; p = 0.039; respectively). ConclusionsStress CMR-inducible myocardial ischemia and LGE have accurate discriminative long-term prognostic value in HFpEF patients without known CAD to predict the occurrence of MACE.

Safety and tolerability of regadenoson in comparison with adenosine stress cardiovascular magnetic resonance: Data from a multicentre prospective registry.

To assess the feasibility and incidence of immediate complications of stress cardiovascular magnetic resonance (CMR) with regadenoson in comparison with adenosine in a large referral population. This is a large, multicenter, prospective registry of vasodilator stress-CMR in a referral population. We recorded the clinical and demographic data, quality of test, CMR findings, hemodynamic data, and complications. Between January 2016 and July 2019, 2908 patients underwent stress-CMR, 2253 with regadenoson and 655 with adenosine. 25.1% of patients had previously known coronary artery disease (CAD). In 305 patients regadenoson was used due to presence of chronic obstructive pulmonary disease (COPD) or asthma, while in 1948 subjects regadenoson was used as first-line vasodilator. Quality was optimal in 90.0%, suboptimal in 9.5%, and poor in 0.5%. Images were diagnostic in 98.9%. After stress with regadenoson, aminophylline 200mg was administered intravenously in all patients. No patient died or had severe immediate complications with regadenoson as opposed to 2 severe bronchospasm with adenosine (p = 0.05). 11 patients (0.5%) had non-severe complications with regadenoson and five patients (0.8%) with adenosine (p = n.s.). Only two patients (0.088%) had non-severe bronchospasm after regadenoson administration. All complications were solved in the CMR unit, with no need for further specific care. Factors significantly associated with presence of complications were history of COPD or asthma and detection of inducible ischaemia. Patients had significantly more minor symptoms when adenosine was used (66.0% vs. 18.4%, p < 0.0001). Stress-CMR with regadenoson is feasible, providing diagnostic information in a referral population. Regadenoson had an excellent safety profile and better tolerability than adenosine, with no serious immediate complications and low incidence of non-severe complications. Only inducible ischaemia and previous history of COPD or asthma were associated with complications after regadenoson-CMR. The incidence of minor symptoms was low.

Evidence and Applicability of Stress Cardiovascular Magnetic Resonance in Detecting Coronary Artery Disease: State of the Art.

Cardiovascular magnetic resonance is increasingly used in clinical practice, as it has emerged over the years as an invaluable imaging technique for diagnosis and prognosis, with clear-cut applications in managing patients with both ischemic and non-ischemic heart disease. In this review, we focus on the evidence and clinical application of stress CMR in coronary artery disease from diagnosis to prognosis.