Myocardial scarring and recurrence of ventricular arrhythmia in patients surviving an out-of-hospital cardiac arrest.

INTRODUCTION: Prediction of recurrent ventricular arrhythmia (VA) in survivors of an out-of-hospital cardiac arrest (OHCA) is important, but currently difficult. Risk of recurrence may be related to presence of myocardial scarring assessed with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Our study aims to characterize myocardial scarring as defined by LGE-CMR in survivors of a VA-OHCA and investigate its potential role in the risk of new VA events. METHODS: Between 2015 and 2022, a total of 230 VA-OHCA patients without ST-segment elevation myocardial infarction had CMR before implantable cardioverter-defibrillator implantation for secondary prevention at Copenhagen University Hospital, Rigshospitalet, and Hospital Clínic, University of Barcelona, of which n = 170 patients had a conventional (no LGE protocol) CMR and n = 60 patients had LGE-CMR (including LGE protocol). Scar tissue including core, border zone (BZ) and BZ channels were automatically detected by specialized investigational software in patients with LGE-CMR. The primary endpoint was recurrent VA. RESULTS: After exclusion, n = 52 VA-OHCA patients with LGE-CMR and a mean left ventricular ejection fraction of 49 ± 16% were included, of which 18 (32%) patients reached the primary endpoint of VA. Patients with recurrent VA in exhibited greater scar mass, core mass, BZ mass, and presence of BZ channels compared with patients without recurrent VA. The presence of BZ channels identified patients with recurrent VA with 67% sensitivity and 85% specificity (area under the ROC curve (AUC) 0.76; 95% CI: 0.63-0.89; p < .001) and was the strongest predictor of the primary endpoint. CONCLUSIONS: The presence of BZ channels was the strongest predictor of recurrent VA in patients with an out of-hospital cardiac arrest and LGE-CMR.

Scar border zone mass and presence of border zone channels assessed with cardiac magnetic resonance imaging are associated with ventricular arrhythmia in patients with ST-segment elevation myocardial infarction.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (CMR) permits characterization of left ventricular ischaemic scars. We aimed to evaluate if scar core mass, border zone (BZ) mass, and BZ channels are risk markers for subsequent ventricular arrhythmia (VA) in ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A sub-study of the DANish Acute Myocardial Infarction-3 multi-centre trial and Danegaptide phase II proof-of-concept clinical trial in which a total of 843 STEMI patients had a 3-month follow-up CMR. Of these, 21 patients subsequently experienced VA during 100 months of follow-up and were randomly matched 1:5 with 105 controls. A VA event was defined as: ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. Ischaemic scar characteristics were automatically detected by specialized software. We included 126 patients with a median left ventricular ejection fraction of 51.0 ± 11.6% in cases with VA vs. 55.5 ± 8.5% in controls (P = 0.10). Cases had a larger mean BZ mass and more often BZ channels compared to controls [BZ mass: 17.2 ± 10.3 g vs. 10.3 ± 6.0 g; P = 0.0002; BZ channels: 17 (80%) vs. 44 (42%); P = 0.001]. A combination of ≥17.2 g BZ mass and the presence of BZ channels was five times more prevalent in cases vs. controls (P ≤ 0.00001) with an odds ratio of 9.40 (95% confidence interval 3.26-27.13; P ≤ 0.0001) for VA. This identified cases with 52% sensitivity and 90% specificity. CONCLUSION(S): Scar characterization with CMR indicates that a combination of ≥17.2 g BZ mass and the presence of BZ channels had the strongest association with subsequent VA in STEMI patients. CLINICALTRIALS.GOV: Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER), NCT01960933 (DANAMI 3-PRIMULTI), and NCT01977755 (Danegaptide).

Left Atrial Remodeling and Cerebrovascular Disease Assessed by Magnetic Resonance Imaging in Continuously Monitored Patients.

BACKGROUND: Atrial remodeling is associated with future atrial fibrillation (AF) and stroke. AF has been associated with cognitive impairment and cerebral white matter lesions. We wished to investigate the possible direct association between atrial remodeling and cerebrovascular disease in patients with and without AF documented by implantable loop recorder (ILR). METHODS: Cardiac and cerebral magnetic resonance imaging were acquired in a cross-sectional study, including participants ≥70 years of age with stroke risk factors without known AF. Cerebrovascular disease was visually rated using the Fazekas scale and number of lacunar strokes. Left atrial (LA) and ventricular volumes and function were analyzed. Associations between atrial remodeling and cerebrovascular disease were assessed with logistic regression models. The analyses were stratified according to sinus rhythm or any AF during 3 months of continuous ILR monitoring to account for subclinical AF. RESULTS: Of 200 participants investigated, 87% had a Fazekas score ≥1 and 45% had ≥1 lacunar infarct. Within 3 months of ILR monitoring, AF was detected in 28 (14%) participants. For participants with sinus rhythm (n = 172), lower LA passive emptying fraction was associated with Fazekas score after multivariable adjustment (OR [95% CI]: 0.51 [0.27; 0.86] p = 0.02), and increased LA maximum (OR [95% CI]: 1.38 [1.07; 1.82] p = 0.01) and minimum volumes (OR [95% CI]: 1.48 [1.03; 2.17] p = 0.04) were associated with lacunar infarcts. There were no significant associations in patients with AF. CONCLUSION: In AF-free patients, as documented by ILR monitoring, we found an independent association between LA passive emptying fraction and Fazekas score and between atrial volumes and lacunar infarcts.

Genome-wide association study identifies 18 novel loci associated with left atrial volume and function.

AIMS: Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA volume and function using cardiac magnetic resonance imaging data. METHODS AND RESULTS: We used the UK Biobank, which is a large prospective population study with available phenotypic and genetic data. On a subset of 35 658 European individuals, we performed genome-wide association studies on five volumetric and functional LA variables, generated using a machine learning algorithm. In total, we identified 18 novel genetic loci, mapped to genes with known roles in cardiomyopathy (e.g. MYO18B, TTN, DSP, ANKRD1) and arrhythmia (e.g. TTN, CASQ2, MYO18B, C9orf3). We observed high genetic correlation between LA volume and function and stroke, which was most pronounced for LA passive emptying fraction (rg = 0.40, P = 4 × 10-6). To investigate whether the genetic risk of atrial fibrillation (AF) is associated with LA traits that precede overt AF, we produced a polygenetic risk score for AF. We found that polygenetic risk for AF is associated with increased LA volume and decreased LA function in participants without AF [LAmax 0.25 (mL/m2)/standard deviation (SD), 95% confidence interval (CI) (0.15; 0.36), P = 5.13 × 10-6; LAmin 0.21 (mL/m2)/SD, 95% CI (0.15; 0.28), P = 1.86 × 10-10; LA active emptying fraction -0.35%/SD, 95% CI (-0.43; -0.26), P = 3.14 × 10-14]. CONCLUSION: We report on 18 genetic loci associated with LA volume and function and show evidence for several plausible candidate genes important for LA structure.

Left atrial volume and function assessed by cardiac magnetic resonance imaging are markers of subclinical atrial fibrillation as detected by continuous monitoring.

AIMS: We aimed to investigate whether left atrial (LA) markers from cardiovascular magnetic resonance (CMR) were able to predict atrial fibrillation (AF) in elderly patients with risk factors for stroke. METHODS AND RESULTS: At baseline, 203 participants with stroke risk factors but without history of AF underwent advanced CMR and received an implantable loop recorder. During a median of 40 (37-42) months of continuous monitoring, incident AF was detected in 79 patients (39%). With regards to CMR markers, a steep increase in incidence rate of AF was seen with LA maximum volume (LAmax) above 55 mL/m2, LA minimum volume (LAmin) above 30 mL/m2, LA total emptying fraction (LA TEF) below 45%, LA active emptying fraction (LA AEF) below 37%, LA strain S below 25%, LA strain A below 17%, and LA strain rate A above -1.7 s-1. After multivariate adjustment, the above-mentioned CMR markers remained associated with AF incidence: hazard ratio (95% confidence interval) 1.25 (1.06-1.48) and 1.51 (1.22-1.87) per 10 mL/m2 increase of LAmax and LAmin, respectively, 1.49 (1.26-1.76) and 1.46 CI (1.25-1.71) per 5% decrease in LA TEF and LA AEF, respectively, 1.23 (1.05-1.44) and 1.56 (1.18-2.06) per 5% decrease in LA strain S and A, respectively, and 2.06 (1.31-3.23) per s-1 increase in LA strain rate A. In prediction analyses, LA functional indices increased area under the receiver operating characteristic curve significantly. CONCLUSION: The risk of AF, including asymptomatic AF, increases significantly with increasing LA volumes and worsening LA function.

Safety of magnetic resonance scanning without monitoring of patients with pacemakers.

AIMS: The objective of this study was to investigate whether it is safe to perform 1.5-Tesla magnetic resonance imaging (MRI) scans in pacemaker (PM) patients without pulse oximetry or electrocardiogram monitoring and with no special specific absorption rate (SAR) or time limits, provided that the PMs are interrogated and programmed to asynchronous mode prior to the scan. METHODS AND RESULTS: This study reports the outcome of 207 MRI scans on PM patients at Rigshospitalet, Copenhagen University Hospital from June 2010 to September 2013. All MRIs were performed with the PMs in asynchronous mode and without additional monitoring. There were no adverse events registered among the PM patients during the study period. The only statistically significant change after MRI scans was a small, but clinically insignificant increase in atrial sense. No occurrences of reprogramming to power-on-reset were registered. CONCLUSION: It is possible to perform MRI scans relatively safely in PM patients without additional monitoring or change in the normal MRI protocol, given that the PM has been assessed and reprogrammed prior to MRI. This is especially important to remember in the acute setting where MRI scans may be delayed when monitoring facilities are unavailable.

Flow measurement at the aortic root - impact of location of through-plane phase contrast velocity mapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the gold standard of cardiac volumetric measurements. Flow in the aortic root is often measured at the sinotubular junction, even though placing the slice just above valve level may be more precise. It is unknown how much flow measurements vary at different levels in the aortic root and which level corresponds best to left ventricle volumetry. METHODS: All patients were older than 70 years presenting with at least one of the following diagnoses: diabetes, hypertension, prior stroke and/or heart failure. Patients with arrhythmias during CMR and aortic stenosis were excluded from the analyses. Stroke volumes were measured volumetrically (SVref) from steady-state free precision short axis images covering the entire left ventricle, excluding the papillary muscles and including the left ventricular outflow tract. Flow sequences (through-plane phase contrast velocity mapping) were obtained at valve level (SVV) and at the sinotubular junction (SVST). Firstly, SVV and SVST were compared to each other and secondly, after excluding patients with mitral regurgitations to ensure that stroke volumes measured volumetrically would theoretically be equal to flow measurements, SVV and SVST were compared to SVref. RESULTS: Initially, 152 patients were included. 22 were excluded because of arrhythmias during scans and 9 were excluded for aortic stenosis. Accordingly, data from 121 patients were analysed and of these 63 had visually evident mitral regurgitation on cine images. On average, stroke volumes measured with flow at the sinotubular junction was 13-16 % lower than when measured at valve level (70.0 mL ±13.8 vs. 81.8 mL ±15.5). This was in excess of the expected difference caused by the outflow to the coronary arteries. In the 58 patients with no valvulopathy, stroke volumes measured at valve level (79.0 mL ±12.4) was closest to the volumetric measurement (85.4 mL ±12.0) but still significantly lower (p < 0.001). Flow measured at the ST-junction (68.1 mL ±11.6) was significantly lower than at valve level and the volumetric measurements. The mean difference between SVref-SVV (6.4 mL) and SVref-SVST (18.2 mL) showed similar variances (SD 7.4 vs. 8.1 respectively) and hence equal accuracy. CONCLUSIONS: Aortic flow measured at valve level corresponded best with volumetric measurements and on average flow measured at the sinotubular junction underestimated flow approximately 15 % compared to valve level. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02036450 . Registered 08/01/2014.

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.

Left atrial late gadolinium enhancement in patients with ischaemic stroke.

AIMS: To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. METHODS AND RESULTS: This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke (<30 days) and 50 age- and sex-matched controls. LA fibrosis assessment was achieved in 78 patients and 45 controls. Blinded to the cardiac magnetic resonance results, strokes were adjudicated according to modified Trial of Org 10172 in Acute Stroke Treatment classification as undetermined aetiology (n = 42) or as attributable to large- or small-vessel disease (n = 36). Patients with stroke had a larger extent of LA fibrosis [6.9%, interquartile range (IQR) 3.6-15.4%] than matched controls (4.2%, IQR 2.3-7.5%; P = 0.007). No differences in LA fibrosis were observed between patients with stroke of undetermined aetiology and those with large- or small-vessel disease (6.6%, IQR 3.8-16.0% vs. 6.9%, IQR 3.4-14.6%; P = 0.73). CONCLUSION: LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.

Atrial cardiomyopathy in patients with ischaemic stroke: a cross-sectional and prospective cohort study-the COAST study.

INTRODUCTION: Despite workup for the aetiology of ischaemic stroke, about 25% of cases remain unexplained. Paroxysmal atrial fibrillation is typically suspected but often not detected. Even if atrial fibrillation (AF) is detected, the quantitative threshold of clinically relevant AF remains unclear. Emerging evidence suggests that left atrial (LA) functional and structural abnormalities may convey a risk of ischaemic stroke in which AF is only one of several features. These abnormalities have been termed 'atrial cardiomyopathy'. This study uses cardiac magnetic resonance (CMR) to evaluate atrial cardiomyopathy among patients with stroke of undetermined aetiology compared with those with an attributable mechanism and controls without established cardiovascular disease. METHODS AND ANALYSIS: This cross-sectional and prospective cohort study included 100 patients with recent ischaemic stroke and 50 controls with no established cardiovascular disease. The study will assess LA structural and functional abnormalities with CMR. Inclusion began in March 2019, and follow-up is planned to be complete in January 2023. There are two scheduled follow-ups: (1) 18 months after individual inclusion, counting from the index diagnostic MRI of the brain, (2) end of study follow-up at 18 months after inclusion of the last patient, assessing the incidence of recurrent ischaemic stroke, AF and cardiovascular death. The primary endpoint is the extent of CMR-assessed atrial fibrosis in the LA at baseline. The study is powered to detect a difference of 6% fibrosis between stroke of undetermined aetiology and stroke of known mechanism with a SD of 9%, a significance level of 0.05, and power of 80%. ETHICS AND DISSEMINATION: This study has been approved by the Danish National Committee on Health Research Ethics (H-18055313). All participants in the study signed informed consent. Results from the study will be published in peer-reviewed journals regardless of the outcome. TRIAL REGISTRATION NUMBER: NCT03830983.

Association between four-dimensional echocardiographic left atrial measures and left atrial fibrosis assessed by left atrial late gadolinium enhancement.

AIMS: Left atrial (LA) fibrosis is a hallmark of atrial cardiomyopathy, and non-invasive surrogate measures of LA fibrosis are therefore needed. We investigated the association between four-dimensional (4D) echocardiographic LA measures and LA fibrosis. METHODS AND RESULTS: A multimodality imaging substudy was performed in a randomized clinical trial (LOOP study), recruiting elderly participants with cardiovascular risk factors. LA late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging was used as a surrogate for LA fibrosis. 4D echocardiographic LA quantification was used to measure maximal and minimal LA volume (LAVmax and LAVmin, respectively), LA emptying fractions (LAEFtotal), and strain. Logistic regression was used to relate LA measures to high LA LGE (≥17 cm2). Of the 44 participants (mean age 76 years, 64% men, median LA LGE 13.1 cm2), 14 exhibited high LA LGE. These participants exhibited abnormalities in several LA functional measures but not LAVmax. In linear regressions, only increasing LAVmin, and decreasing LAEFtotal, and reservoir strain were associated with increasing LA LGE. Furthermore, increasing LAVmin was associated with a higher likelihood of high LA LGE [odds ratio (OR) = 1.19 (1.04-1.37)]. Decreasing LAEFtotal and reservoir strain were also associated with higher likelihood of LA LGE [OR = 1.18 (1.05-1.33)] and OR = 1.15 (1.02-1.30), per 1% decrease in LAEFtotal and reservoir strain, respectively]. These findings were consistent after multivariable adjustments. LAEFtotal provided the highest performance for detecting high LA LGE (area under the curve of 0.78). CONCLUSION: LAVmin, LAEFtotal, and reservoir strain measured by 4D echocardiography are significantly associated with LA LGE. LAEFtotal provides the best performance for detecting high LA LGE.

Accuracy, analysis time, and reproducibility of dedicated 4D echocardiographic left atrial volume quantification software.

Four-dimensional (4D) echocardiography may provide more accurate estimations of left atrial (LA) volumes than 2-dimensional (2D) measures. We sought to compare the concordance of a novel 4D LA quantification software versus 2D echocardiography against cardiac magnetic resonance (CMR). This was a multimodality imaging substudy of a randomized clinical trial (the LOOP study). Elderly participants with stroke risk factors were included. A subgroup of this study population underwent transthoracic echocardiography (n = 1441) and a subset underwent CMR within two weeks (n = 73). The mean age of the echocardiographic study population was 74 years and 54% were men. The maximal LA volume (LAVmax) was 47 mL by 2D, 52 mL by 4D, and 104 mL by CMR. While 2D echocardiography showed a moderate correlation with 4D (R2 = 0.51) it yielded significantly lower values for LAVmax with a mean difference of 4.5 ± 11.9 mL, p < 0.001. 4D echocardiography correlated strongly with CMR measurements (R2 = 0.70), whereas 2D echocardiography showed a moderate correlation (R2 = 0.53). However, both modalities systematically underestimated LAVmax largely compared to CMR (2D vs. CMR: - 54.9 ± 21.3 mL; 4D vs. CMR: - 49.7 ± 18.6 mL). Similar observations were made for minimal LA volume and LA volume before atrial contraction. Analyses time by 4D was shorter than for 2D (90 ± 11 vs. 118 ± 16 s, p < 0.001). Intra- and interobserver variability was lower for 4D than 2D. Four-dimensional echocardiography is faster, more reproducible, and correlates more closely to CMR than 2D echocardiography. Both 4D and 2D echocardiography systematically underestimates LA volumes compared to CMR, emphasizing that values of LA volumes are not interchangeable between echocardiography and CMR.

Impact of age on reperfusion success and long-term prognosis in ST-segment elevation myocardial infarction - A cardiac magnetic resonance imaging study.

BACKGROUND: Coronary collateral circulation and conditioning from remote ischemic coronary territories may protect culprit myocardium in the elderly, and younger STEMI patients could suffer from larger infarcts. We evaluated the impact of age on myocardial salvage and long-term prognosis in a contemporary STEMI cohort. METHODS: Of 1603 included STEMI patients 807 underwent cardiac magnetic resonance. To assess the impact of age on infarct size and left ventricular ejection fraction (LVEF) as well as the composite endpoint of death and re-hospitalization for heart failure we stratified the patients by an age cut-off of 60 years. RESULTS: Younger STEMI patients had smaller final infarcts (10% vs. 12%, P = 0.012) and higher final LVEF (60% vs. 58%, P = 0.042). After adjusting for multiple potential confounders age did not remain significantly associated with infarct size and LVEF. During 4-year follow-up, the composite endpoint occurred less often in the young (3.2% vs. 17.2%; P < 0.001) with a univariate hazard ratio of 5.77 (95% CI, 3.75-8.89; p < 0.001). Event estimates of 4 subgroups (young vs. elderly and infarct size beyond vs. below median) showed a gradual increase in the occurrence of the composite endpoint depending on both age and acute infarct size (log-rank p < 0.001). CONCLUSION: Having a STEMI after entering the seventh decade of life more than quadrupled the risk of future death or re-hospitalization for heart failure. Risk of death and re-hospitalization depended on both advanced age and infarct size, albeit no substantial difference was found in infarct size, LVEF and salvage potential between younger and elderly patients with STEMI.

Ischemia From Nonculprit Stenoses Is Not Associated With Reduced Culprit Infarct Size in Patients with ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: In patients with ST-segment-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention, reperfusion injury accounts for a significant fraction of the final infarct size, which is directly related to patient prognosis. In animal studies, brief periods of ischemia in noninfarct-related (nonculprit) coronary arteries protect the culprit myocardium via remote ischemic preconditioning. Positive fractional flow reserve (FFR) documents functional significant coronary nonculprit stenosis, which may offer remote ischemic preconditioning of the culprit myocardium. The aim of the study was to investigate the association between functional significant, multivessel disease (MVD) and reduced culprit final infarct size or increased myocardial salvage (myocardial salvage index [MSI]) in a large contemporary cohort of STEMI patients. METHODS: Cardiac magnetic resonance was performed in 610 patients with STEMI at day 1 and 3 months after primary percutaneous coronary intervention. Patients were stratified into 3 groups according to FFR measurements in nonculprit stenosis (if any): angiographic single vessel disease (SVD), FFR nonsignificant MVD (functional SVD), or FFR-significant, functional MVD. RESULTS: A total of 431 (71%) patients had SVD, 35 (6%) had functional SVD, and 144 (23%) had functional MVD. There was no difference in final infarct size (mean infarct size [%left ventricular mass] SVD, 9±3%; functional SVD, 9±3%; and functional MVD, 9±3% [P=0.82]) or in MSI between groups (mean MSI [%left] SVD, 66±23%; functional SVD, 68±19%; and functional MVD, 69±19% [P=0.62]). In multivariable analyses, functional MVD was not associated with larger MSI (P=0.56) or smaller infarct size (P=0.55). CONCLUSIONS: Functional MVD in nonculprit myocardium was not associated with reduced culprit final infarct size or increased MSI following STEMI. This is important knowledge for future studies examining a cardioprotective treatment in patients with STEMI, as a possible confounding effect of FFR-significant, functional MVD can be discarded. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

Cardiac magnetic resonance systematically overestimates mitral regurgitations by the indirect method.

OBJECTIVE: Cardiac MRI is quickly emerging as the gold standard for assessment of mitral regurgitation, most commonly with the indirect method subtracting forward flow in aorta from volumetric segmentation of the left ventricle. We aimed to investigate how aortic flow measurements with increasing distance from the aortic valve affect calculated mitral regurgitations and whether measurements were influenced by breath-hold regimen. METHODS: Free-breathing and breath-hold phase contrast flows were measured in aorta at valve level, sinotubular (ST) junction, mid-ascending aorta and in the pulmonary trunk. Flow measurements were pairwise compared, and subsequently, after exclusion of patients with visible mitral and tricuspid regurgitations for left-sided and right-sided comparisons, respectively, flow-measured stroke volumes were compared with ventricular volumetric segmentations. RESULTS: Thirty-nine participants without arrhythmias or structural abnormalities of the large vessels were included. Stroke volumes measured with free-breathing and breath-hold flow decreased equally with increasing distance to the aortic valves (breath-hold flow: aortic valve 105.6±20.8 mL, ST junction 101.5±20.7 mL, mid-ascending aorta 98.1±21.5 mL). After exclusion of atrioventricular regurgitations, stroke volumes determined by volumetric measurements were higher compared with values determined by flow measurements, corresponding to 'false' atrioventricular regurgitations of 8.0%±5.8% with flow measured at valve level, 11.6%±5.2% at the ST junction and 15.3%±5.0% at the mid-ascending aorta. CONCLUSIONS: Stroke volumes determined by flow decrease throughout the proximal aorta and are systematically lower than volumetrically measured stroke volumes. The indirect method systematically overestimates mitral regurgitations, especially with increasing distance from the aortic valves.

Verification of threshold for image intensity ratio analyses of late gadolinium enhancement magnetic resonance imaging of left atrial fibrosis in 1.5T scans.

The use of cardiovascular magnetic resonance imaging left atrial late gadolinium enhancement (LA LGE) is increasing for fibrosis evaluation though the use is still limited to specialized centres due to complex image acquisition and lack of consensus on image analyses. Analysis of LA LGE with image intensity ratio (IIR) (pixel intensity of atrial wall normalized by blood pool intensity) provides an objective method to obtain quantitative data on atrial fibrosis. A threshold between healthy myocardium and fibrosis of 1.2 has previously been established in 3T scans. The aim of the study was to reaffirm this threshold in 1.5T scans. LA LGE was performed using a 1.5T magnetic resonance scanner on: 11 lone-AF patients, 11 age-matched healthy volunteers (aged 27-44) and 11 elderly patients without known history of AF but varying degrees of comorbidities. Mean values of IIR for all healthy volunteers +2SD were set as upper limit of normality and was reproduced to 1.21 and the original IIR-threshold of 1.20 was maintained. The degree of fibrosis in lone-AF patients [median 9.0% (IQR 3.9-12.0)] was higher than in healthy volunteers [2.8% (1.3-8.3)] and even higher in elderly non-AF [20.1% (10.2-35.8), p = 0.001]. The previously established IIR-threshold of 1.2 was reaffirmed in 1.5T LA LGE scans. Patients with lone AF presented with increased degrees of atrial fibrosis compared to healthy volunteers in the same age-range. Elderly patients with no history of AF showed significantly higher degrees of fibrosis compared to both groups with younger individuals.

Early-onset atrial fibrillation patients show reduced left ventricular ejection fraction and increased atrial fibrosis.

Atrial fibrillation (AF) has traditionally been considered an electrical heart disease. However, genetic studies have revealed that the structural architecture of the heart also play a significant role. We evaluated the functional and structural consequences of harboring a titin-truncating variant (TTNtv) in AF patients, using cardiac magnetic resonance (CMR). Seventeen early-onset AF cases carrying a TTNtv, were matched 1:1 with non-AF controls and a replication cohort of early-onset AF cases without TTNtv, and underwent CMR. Cardiac volumes and left atrial late gadolinium enhancement (LA LGE), as a fibrosis proxy, were measured by a blinded operator. Results: AF cases with TTNtv had significantly reduced left ventricular ejection fraction (LVEF) compared with controls (57 ± 4 vs 64 ± 5%, P < 0.001). We obtained similar findings in early-onset AF patients without TTNtv compared with controls (61 ± 4 vs 64 ± 5%, P = 0.02). We furthermore found a statistically significant increase in LA LGE when comparing early-onset AF TTNtv cases with controls. Using state-of-the-art CMR, we found that early-onset AF patients, irrespective of TTNtv carrier status, had reduced LVEF, indicating that early-onset AF might not be as benign as previously thought.

Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders.

OBJECTIVES: The authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population. BACKGROUND: LA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown. METHODS: Cardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. RESULTS: Patients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm2 increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm2 increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. CONCLUSIONS: Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450).

Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction: A DANAMI-3 sub-study.

AIMS: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47-36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07-50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27-47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83-328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. CONCLUSION: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.

Assessment of the myocardial area at risk: comparing T2-weighted cardiovascular magnetic resonance imaging with contrast-enhanced cine (CE-SSFP) imaging-a DANAMI3 substudy.

AIMS: Myocardial salvage following treatment for ST-segment elevation myocardial infarction is prognostic for morbidity and mortality. Studies with myocardial salvage as endpoint rely on valid assessment of the myocardial area at risk (AAR). T2-weighted cardiovascular magnetic resonance (CMR) imaging is the preferred method to assess the AAR. However, T2-weighted imaging can be of poor image quality and uninterpretable. Contrast-enhanced (CE) cine imaging can also show AAR and our aim was to investigate if CE-cine can replace T2-weighted imaging. Cine imaging is part of a standard CMR-protocol and implementing CE-cine imaging for assessment of the AAR would mean shorter investigation time. METHODS AND RESULTS: As a DANAMI-3 substudy, we performed successful dual imaging of the AAR in 166 participants using both T2-weighted short tau inversion recovery (T2-STIR) and CE-cine imaging. T2-STIR imaging was non-diagnostic in nine and CE-cine in one scan during the period. CE-cine measured 4.7% of left ventricle (LV) [95% confidence interval 3.2-6.2%] smaller AAR compared with T2-STIR images (P < 0.001). Visual analysis of a plot of infarct size vs. AAR showed an overestimation of the AAR when measured with T2-STIR images. There was no difference in AAR with CE-cine in an interobserver analysis of 46 scans [1.2 g (standard deviation 9.5), P = 0.42]. CONCLUSIONS: CE-cine imaging shows good internal consistency in assessment of the AAR. A visual inspection reveals possible overestimation of AAR with T2-STIR images. There is good interobserver agreement in the analysis of CE-cine imaging. CE-cine can replace T2-STIR imaging resulting in a more valid assessment of the myocardial AAR.