Cardiac Magnetic Resonance Study Research Articles

Evaluation of the prognostic value of lateral MAPSE in patients with suspected coronary artery disease

ObjectivesTo evaluate the prognostic value of lateral mitral annular plane systolic excursion (MAPSE) in the prediction of major adverse cardiology events (MACE) in patients with suspected coronary artery disease (CAD). Methods233 consecutive patients were enrolled with suspected CAD from October 2012 to September 2013 and performed contrast-enhanced cardiac magnetic resonance (CMR) and two-dimensional echocardiogram studies no later than 72 h after admission. CMR imaging protocol included 4-chamber cine(cine-CMR), cardiovascular magnetic resonance angiography (CMRA) and late gadolinium enhancement (LGE). The primary endpoint is the time of first occurrence of a MACE The independent association between lateral MAPSE and MACE was evaluated by Kaplan-Meier analysis and multivariable Cox regression analysis. C statistic and net reclassification improvement (NRI) were used to evaluate the prognostic value of lateral MAPSE in MACE. ResultsForty-five MACE occurred during an average follow-up of 9.2 years. Patients with lateral MAPSE＜9.885 mm experienced a significantly higher incidence of MACE than patients with lateral MAPSE ≥ 9.885 mm (P＜0.001). After adjustment for established univariate predictors (age, diabetes, hypertension, hypercholesterolemia, transmural myocardial infarction), lateral MAPSE remained a significant independent predictor of MACE (HR = 1.373; P = 0.020). The incorporation of lateral MAPSE into the risk model resulted in significant improvement in C statistic (increasing from 0.668 to 0.844; P = 0.005). NRI improvement was 0.33 (P＜0.001). Conclusionslateral MAPSE derived from cine-CMR is an independent predictor of MACE, and improve risk reclassification beyond traditional clinical and CMR risk factors in patients with suspected coronary disease.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS>29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

Left atrioventricular coupling index is an independent associate of new-onset AF and stroke in hypertrophic cardiomyopathy: a CMR study

Abstract Background Left atrial (LA) dysfunction is an important marker of disease progression in hypertrophic cardiomyopathy (HCM). LA volumes and functional parameters are associated with new-onset atrial fibrillation (AF) and its complications including stroke. The association between left atrioventricular coupling (LACI), a parameter reflecting the contribution of the left ventricular and LA remodeling to LA dysfunction, with the occurrence of new-onset AF and stroke has not been evaluated. Aim To investigate the association between LACI and the occurrence of new-onset AF or stroke in patients with HCM. Methods In patients with an established diagnosis of HCM and cardiac magnetic resonance (CMR) data, LACI was calculated as the ratio between the LA and the LV end-diastolic volumes. New-onset AF or occurrence of stroke comprised the primary combined endpoint. Cumulative event-free survival rates for the occurrence of the primary endpoint were estimated with the population divided according to a LACI cut-off value of 40%. The association between clinical and CMR variables and the primary endpoint was assessed with univariable and multivariable Cox proportional hazard regression models. Results Of 114 patients with HCM, (mean age 54±16 years, 33 (29%) female, LV ejection fraction 67.0±8.4%), 71 patients (49%) had a LACI > 40% (left atrioventricular uncoupling). During a median follow-up of 4.1 (1.8-6.4) years, 19 (16.7%) patients experienced new-onset AF or stroke. Patients with preserved left atrioventricular coupling (LACI ≤ 40%) had a lower cumulative rate of events compared to those with left atrioventricular uncoupling (log-rank p=0.031, Fig. 1). LACI was independently associated with new-onset AF or stroke after adjusting by the presence of late gadolinium enhancement (LGE) sex and age (HR=23.27, p=0.016). Conclusions In patients with HCM, the presence of left atrioventricular uncoupling is independently associated with the occurrence of new-onset AF or stroke.

Prevalence of cardiomyopathies and myocardial scar in patients with non-complicated premature ventricular beats: a CMR study

Abstract Introduction Frequent or symptomatic premature ventricular beats (PVBs) in subjects with no personal or family history of cardiac disease or sudden death is a recurrent motive for cardiac magnetic resonance (CMR) prescriptions. This represents a significant burden on healthcare services, given the low availability of CMR technique. If CMR is a recommended imaging modality in patients with history of cardiac arrest due to ventricular arrhythmia, sustained ventricular arrhythmias or when first-line tests are abnormal, its diagnostic value in this specific setting has not been evaluated. Purpose To determine the prevalence of significant CMR abnormalities (myocardial fibrosis, arrhythmogenic cardiomyopathies) in patients with no personal nor family history of cardiac disease and non-complicated PVBs. Methods Between September 2010 and July 2021, 416 healthy adults with no personal nor family cardiac disease history underwent CMR at our institution to explore non complicated PVBs, and were retrospectively included (Figure 1). Right and left ventricular (RV/LV) function and dimensions were systematically evaluated on CMR, as the presence of myocardial late gadolinium enhancement (LGE). Criteria for cardiomyopathies (hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), ARVD), the presence and location of myocardial fibrosis were looked after. Results A total of 605 patients were referred for CMR to explore frequent PVBs, representing 14% of all tests performed during this period. Among them, 12 patients (3%) presented significant myocardial abnormalities possibly related to PVBs: 2 patients had sequelae of myocardial infarction and 3 of myocarditis, 1 patient had criteria of HCM and 1 of ARVD, finally 5 presented non-specific myocardial fibrosis (septal mid-wall LGE). In addition, after a mean follow-up of 5 years, there was no death in patients with abnormal CMR, and only 2 patients underwent transcatheter ablation for focal non complicated but symptomatic PVBs. There was no hospitalization for heart failure. Conclusion In patients with non-complicated PVBs and no history of cardiac disease, the rate of cardiomyopathy pattern or myocardial scar on CMR is very low (3%). In this specific population, events were very rare: frequent isolated PVBs, even when associated with myocardial abnormalities, were a benign condition in our study. Given the high volume of patients referred for this indication in daily practice (14% of total CMRs in our center), the limited availability and high costs of CMR, and the difficulties of CMR sequences acquisition in the context of frequent PVBs (possibly leading to misdiagnosis), these data suggest that we should refine the selection of patients undergoing CMR for PVBs exploration.

Postoperative assessment of interstitial myocardial fibrosis in aortic valve pathologies: insights from a cardiac magnetic resonance study

Abstract Background Data on the characteristics of diffuse myocardial fibrosis (DMF) among patient undergoing valve surgery for aortic regurgitation (AR), high-gradient aortic stenosis (HG-AS), and low-flow low-gradient aortic stenosis with low ejection fraction (LFLG-AS) are limited. Purpose To assess the postoperative characteristics of DMF and to compare post- and pre-operative cardiac magnetic resonance imaging (CMR) data. Methods Patients diagnosed with AR (38), HG-AS (62), and LFLG-AS (39), who met criteria for surgical intervention, were prospectively included. Pseudo-severe AS was excluded. Post-operative CMR was performed 6 to 8 months after surgery, and a comparison between post- and pre-operative data was made (delta=Δ). Quantitative analysis included assessment of extracellular volume fraction (ECV), indexed ECV (iECV), and myocardial mass (MM). Results There were differences in baseline characteristics among patients with AR, HG-AS, and LFLG-AS concerning age (54±14 vs 63±8 vs 67±8 years, respectively; p<0.01), male gender (75% vs 50% vs 82%, respectively; p<0.01), NYHA functional class III and IV (37.5% vs 55.2% vs 30.8%, respectively; p=0.03), EuroSCORE II (1.16±0.5 vs 1.26±0.46 vs 3.39±2.65%, respectively; p<0.01), and STS (0.74±0.29 vs 1.11±0.5 vs 3.21±2.11%, respectively; p<0.01). Global ECV was similar between groups (29.2±5.6 vs 27.0±3.6 vs 29.4±5.9%, respectively; p=0.01), MM was different between groups (215±76 vs 161±51 vs 203±51g, respectively; p<0.01), and iECV was different between groups and significantly higher in AS patients (50.1±31.0 vs 21±8 vs 34.2±10.2ml/m², respectively; p<0.01). All patients underwent valve surgery and there were differences regarding extracorporeal circulation time (94±25 vs 97±20 vs 75±41min, respectively; p<0.01), and 30-day mortality (0% vs 3% vs 15%, respectively; p<0.01). Post-surgery data from patients with AR (32), HG-AS (62), and LFLG-AS (21) demonstrated a comparable decrease across all groups concerning preoperative MM (ΔMM: -39.3±41.5 vs -33.4±30.9 vs -23.4±34.2g, respectively; p=0.36) (Figure 1). In contrast, iECV decreased post-surgery only in AR, remaining stable in HG-AS and LFLG-AS (ΔiECV: -19.1±22.5 vs -1.4±7.4 vs 0.9±12ml/m², respectively; p<0.01). Thus, postoperative ECV maintained commensurate values in AR, while increasing in HG-AS and LFLG-AS (ΔECV: -0.1±4.5 vs 1.5±5.1 vs 2.9±4.9%, respectively; p=0.09). Δ left ventricular ejection fraction (LVEF) was similar across groups (ΔLVEF: -1.5±10.6 vs 1.1±11.7 vs 2.6±16%, respectively; p=0.44). Conclusion In the postoperative period, a decrease in MM was observed in all groups of aortic valve pathologies. However, only patients with AR showed a simultaneous and proportional reduction in DMF mass, explaining the patterns of ECV variation. Thus, the reduction of DMF in the postoperative period appears to vary according to the phenotypes presented, and patients with AR exhibit early reverse remodeling despite having high levels of DMF.Delta iECV, LV mass and ECV measures

Left atrial remodeling and novel biomarkers in obese patients with heart failure with preserved ejection fraction compared to type-2-diabetics and obese controls: a cardiac magnetic resonance study

Abstract Background Elevated filling pressures and subsequent left atrial (LA) dilation are common findings in heart failure with preserved ejection fraction (HFpEF), reflecting a chronic state of the disease and holding prognostic value. HFpEF is thought to develop through a long-term pro-inflammatory state triggered by comorbidities, such as obesity and type 2 diabetes mellitus (T2DM). Emerging biomarkers have shown associations with structural remodeling, but also increased myocardial stiffness. Purpose To elucidate the relationship between LA volume and function, and prognostic biomarkers (NT-proBNP, BNP-32, IL1R1, Galectin-3, and Pentraxin-3) in an obese cohort with T2DM or HFpEF and T2DM, versus healthy obese controls. Methods We conducted a prospective cohort study of 35 obese participants, divided into three groups: T2DM (n=16), HFpEF with T2DM (NYHA II-III, n=13), and healthy obese controls (n=6). Each subject underwent comprehensive CMR at a 3T scanner to assess LA strain and volume. Atrial strain was assessed on 2- and 4-chamber view cine images by experienced CMR investigators using dedicated software. Routine labs and serum levels of biomarkers were measured. If labs or images were repeated, the average was calculated. Statistical significance was determined through ANOVA and student’s t-test for group comparisons and Pearson correlation for associations between LA parameters and biomarker levels. Results Cohorts were evenly matched in terms of demographics, vital signs, and ventricular volumes and functions, as depicted in Table 1. Only one patient in the HFpEF subgroup reported history of atrial fibrillation. Both minimum and maximum LA volumes were significantly elevated in the HFpEF group compared to the T2DM and control groups (p < 0.018). LA strain (conduit, reservoir, and booster) was notably compromised in the HFpEF cohort, contrasting with the obese T2DM group where LA strain values did not differ significantly from those observed in obese controls (Figure 1). Biomarker analysis revealed a marked increase of NT-proBNP, BNP-32, Galectin-3, and Pentraxin-3 in the HFpEF cohort. In the HFpEF cohort, IL1R1 was the only biomarker that was strongly associated with higher left ventricular enddiastolic (r=0.69, p=0.003) and endsystolic volumes (r=0.75, p=0.009). Moreover, IL1R1 was the only biomarker associated with atrial functional changes (booster strain, r=-0.57, p=0.043) in the HFpEF patients. Our findings indicate that ILR1 plays a crucial role in the cardiometabolic (obesity-T2DM) HFpEF phenotype, with its activation leading to advanced cardiac remodeling. Conclusion Obese HFpEF patients with T2DM showed severely altered left atrial morphology and function compared to those that are only obese or obese with T2DM. Moreover, our findings revealed that atrial remodeling in this population is driven by pro-fibrotic inflammatory pathways.Characteristics of the study cohortLeft atrial strain analysis

Mortality and heart failure in patients with severe tricuspid regurgitation. Impact of RV volumes and function by CMR.

Abstract Background Beyond symptoms, right ventricle (RV) dilatation and dysfunction are established criteria for intervention in patients with significant tricuspid regurgitation (TR); however defined thresholds to support intervention are lacking. As a result, the optimal timing for intervention remains controversial and it is commonly undertaken at a late stage. Purpose To describe prognostic cut-off values of RV size and function by Cardiac Magnetic Resonance in a multicentre cohort of patients with at least severe TR. Methods The study enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. Conventional parameters of biventricular volume and function were assessed in all patients. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 28 months (IQR: 10-54 months), 42% of the patients (n=134) experienced the combined endpoint (n=113 were admitted due to HF, n=61 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in a multivariate Cox proportional model (LR Chi-Square: 88.01, p<0.001), RV-EDV and RVEF were independently associated with all-cause mortality and heart failure (adjusted HR for RV-EDV per ml/m2 =1.008 [1.005-1.012], p<0.001 and RVEF HR per 1%=0.961 [0.942-0.981], p<0.001). Thresholds of RV-EDV ≥ 93 ml/m2, RV-ESV ≥ 39 ml/m2 and RVEF ≤ 58% held the best accuracy to predict outcomes (figure). In multivariable analysis, prognostic cut-off values of RV-EDV, RV-ESV and RVEF was associated with 1.91, 2.03, and 1.76-fold increased risk of HF or all-cause mortality respectively (RV-EDV HR: 1.91 [1.34-2.71], p<0.001, RV-ESV HR 2.03 [1.42-2.89], p<0.001 and RVEF HR1.76 [1.25-2.49], p=0.001). Conclusion RV size and function are crucial for determining optimal timing for TR intervention. CMR remains the gold standard to assess RV remodeling. Cut-off values of RV volume and function by CMR are defined in a multicentre cohort of patients based on outcome data; proposed thresholds differ from those previously established by echocardiography.Kaplan Meier curves

LV reverse remodeling after SAVR in patients with severe symptomatic aortic stenosis: impact on the clinical outcome

Abstract Introduction Surgical aortic valve replacement (SAVR) is the treatment of choice for young patients with severe aortic stenosis (AS) and low surgical risk. Left ventricular (LV) reverse remodeling (RR) after surgery is expected to occur. However, this is not always the case following afterload relief, and this may impact the prognosis. We aimed to assess the prognostic effect of distinct definitions of LV RR after SAVR in the long-term outcome of patients with severe AS. Methods Single-centre prospective study including patients referred for SAVR due to severe symptomatic AS, with no previous history of ischemic cardiomyopathy. Both pre- and post-operative transthoracic echocardiographic (TTE) and cardiac magnetic resonance (CMR) study (at the 3rd to 6th month after SAVR) were performed. LV RR was defined when in presence of at least one of the imaging criteria: >15% decrease in end-diastolic volume (EDV) by CMR; >15% decrease in LV indexed mass (LVM) by CMR; >10% decrease in geometric remodeling (LV mass/EDV ratio) by CMR; >10% increase in LV ejection fraction (LVEF) by CMR; >50% increase on global longitudinal strain (GLS) by TTE. We assess the prognostic value of RR definitions for the outcome after SAVR using Cox regression and Kaplan-Meier analysis. The primary endpoint was defined as all-cause mortality, heart failure (HF) hospitalization or worsening HF. Results We enrolled 140 patients – mean age 71±9 years-old, 49% male, predominantly high-gradient-normal flow AS (mean gradient 65±18mmHg, aortic valve area 0.7±0.2cm2, index stroke volume 47±11mL/m2) submitted to SAVR. At a mean follow-up (FUP) of 34±12 months, 23 (16%) patients met the primary endpoint: 4% (5 patients) died immediately after surgery; three patients died at the FUP (overall mortality rate of 6%). 12 patients (9%) were admitted for HF and 7 (5%) had at least one episode of worsening HF. 118 patients had complete pre and post-surgery imaging study (mean FUP: 36±10 months): 103 patients (87%) had at least one RR parameter (Table 1). Post-operative RR was not independently associated with the clinical outcome (Figure 1A). LVM was the sole independent predictor of the outcome at univariate analysis (Figure 1B–F). Conclusions LV RR after SAVR is highly prevalent in a cohort of patients with classical severe symptomatic AS. However, only LVM regression independently predicts the clinical outcome after surgery. This may stand the greater importance of structural reverse remodeling, rather than LV functional improvement, after pressure overload relief.

Gender-specific differences in severe tricuspid regurgitation. Finding from a TR multicentre CMR registry

Abstract Background Observational studies have suggested that severe tricuspid regurgitation (TR) is more prevalent in women than in men, although the pathophysiological causes that justify this difference are unknown. Purpose 1) to assess clinical and imaging differences by Cardiac Magnetic Resonance (CMR) between men and women and 2) to examine the relationship between gender and all-cause mortality in a multicentre cohort of patients with at least severe TR. Methods The study-enrolled patients with at least severe TR assessed by 2D echocardiography who underwent a contemporary cardiac magnetic resonance (CMR) study. The primary outcome was all-cause mortality. Results 318 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (70 ± 11 years, 67% female, 73% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. Women showed a non-significant tend to lower prevalence of comorbidities, lower BNP and significantly lower creatinine values (table). Regarding CMR variables, women showed smaller indexed right ventricle (RV) volumes higher RVEF and lower TR regurgitant volume (table, p<0.05 for all). Left ventricle (LV) volumes were smaller and LVEF higher in women compared to men (p<0.001). During a median follow-up of 28 months (IQR: 10-54 months), there were 61 deaths (19%) with an estimated 5-year survival of 74%. Cumulative all-cause mortality was significantly worse in men compared to women (27% vs. 15%, p<0.001, figure). Male gender was significantly associated with all-cause mortality independently of age, RV volumes, RVEF and LVEF (HR 2,2 [1.34-3,68], p =0.002). Different cut-off values of index RV volumes and EF were predictive of mortality in men and women. In men a RV-EDV >110 ml/m2 and RVEF<57%; in women a RV-EDV >90 ml/m2 and RVEF< 60% were predictive of all-cause mortality (p<0.01). Conclusion Severe TR is more prevalent in women; however, it shows lower RV remodeling, better RV function and lower rate of events compared to men. Different prognostic RV cut-off values are provided based on CMR data.Gender differencesKaplan Meier Curves

Effective RV ejection fraction by CMR: a new index of RV function in patients with severe TR

Abstract Background Right ventricle (RV) dysfunction represent an formal indication for intervention in patients with significant tricuspid regurgitation (TR). RV ejection fraction (RVEF) by Cardiac Magnetic Resonance (CMR) is considered the gold standard of RV function; however it is influenced by changes of preload conditions and may remain unaffected until late stages in severe TR. Effective RV ejection fraction (eRVEF) is corrected by the amount of TR and may reflect an earlier parameter of RV dysfunction. Purpose To compare the prognostic impact of both indices of RV function: RVEF and eRVEF in a multicentre cohort of patients with severe TR. Methods Patients with at least severe TR assessed by 2D echocardiography with a contemporary cardiac magnetic resonance (CMR) study were included in this study. In addition to conventional parameters of biventricular volume and function, eRVEF was assessed in all patients. eRVEF was calculated according to the formula: eRVEF=net pulmonary forwardflow/RV− EDV (figure). A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined. Results 271 patients with severe TR recruited from 5 tertiary care hospitals were included in this study (age 71 ± 11 years, 67% female, 83% NYHA I or II). Regarding the etiology, 10% were primary TR, 1% CIED-related TR, 46 % atrial secondary TR and 43% ventricular secondary TR. After a median follow-up of 27 months (IQR: 10-53 months), 41% of the patients (n=112) experienced the combined endpoint (n=97 were admitted due to HF, n=49 died). After adjusting for age, NYHA class, comorbidities, type of TR and LVEF in multivariate Cox proportional models, both RVEF and eRVEF were independently associated with all-cause mortality and heart failure (adj HR for RVEF HR per 1%=0.96 [0.94-0.98], p<0.001 and for eRVEF per 1%=0.98 [0.96-0.99], p<0.001). A value of eRVEF of ≤37% were associated with impaired prognosis (figure). eRVEF identified higher rates of RV dysfunction compared to RVEF (49% vs 38%, p<0.001). eRVEF was superior to RVEF to predict outcomes (higher AUC 0.70 [0.63-0.76] vs 0.66 [0.59-0.73, p<0.001; Δ C-statistic 0.139 [0.040-0.237], p=0.05). Conclusion RV function is crucial for determining optimal timing for TR intervention. eRVEF is corrected by the amount of TR and identify higher rates of RV dysfunction in severe TR. eRVEF held stronger association with outcome compared to RVEF.eRVEF calculationKaplan Meier Curves

The clinical impact of cardiac magnetic resonance imaging upon suspected myocardial infarction with non-obstructive coronary artery disease

Abstract Background Cardiac magnetic resonance (CMR) may identify the underlying pathology in myocardial infarction with non-obstructed coronary arteries (MINOCA), however there are scant prospective data evaluating the more important measure of actual change in diagnosis and management consequent to CMR. Purpose To evaluate impact of CMR in MINOCA upon diagnosis, diagnostic certainty and management, adjudicated by treating physicians to minimise investigator bias. Methods Prospective, multi-center international pre- and post-CMR study of suspected MINOCA. Physician diagnosis, diagnostic certainty and intended management were established by questionnaire before and after CMR. The primary outcome was change in diagnosis or management. Secondary outcomes were change in diagnosis, change in management, change in diagnostic certainty, and number-needed-to-test for de-prescription of dual antiplatelet therapy (DAPT). Potential predictors of impactful CMR were evaluated by multivariable logistic regression analysis. Results 320 patients referred by 74 clinicians underwent CMR; mean age 55.6 (12.3) years, 48.1% female. CMR was conducted at median 11 days (IQR 6-19) post presentation. CMR led to change in diagnosis or management in 62.8% (95% CI 57.4% - 68.2%, p<0.0001) and significantly increased diagnostic certainty [8/10 post-CMR (5-9) vs 6/10 pre-CMR (4-7), p<0.0001]. Predictors of impactful CMR on multivariable analysis were early CMR (≤14 days), absence of atheroma on coronary angiography, significant pre-CMR diagnostic uncertainty (≤5/10), and a history of vascular disease. DAPT was deprescribed or modified to single antiplatelet in 61.7% patients. The number-needed-to-test to deprescribe DAPT was 2.6 (and 1.6 if a myocardial infarction mimic was co-suspected pre-CMR), which has important cost-benefit implications for CMR in MINOCA. Conclusions In this first prospective multi-centre study of CMR in MINOCA where diagnostic utility was adjudicated by the treating physicians, CMR was associated with frequent and significant changes in diagnosis, clinician certainty and clinical care, including frequent de-prescription of DAPT. Early CMR is to be encouraged, particularly in patients where there is significant diagnostic uncertainty and no atheroma on coronary angiography.

Study design of the CARDIO-TTRansform cardiac magnetic resonance imaging substudy

Abstract Background Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping can track treatment response in patients with cardiac amyloidosis by assessing changes in cardiac amyloid burden along with associated changes in structure and function. The CARDIO-TTRansform trial is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial designed to assess the efficacy and safety of eplontersen in transthyretin amyloid cardiomyopathy (ATTR-CM). Eplontersen is a ligand-conjugated antisense oligonucleotide designed to reduce hepatic production of transthyretin protein, the amyloid fibril precursor protein in ATTR-CM. Patients with hereditary or wild-type ATTR-CM on available standard of care were randomized 1:1 to receive 45 mg of eplontersen or placebo via subcutaneous injection every 4 weeks. Patients in the main study with no contraindication to CMR were invited to participate in this sub-study. Purpose The primary objective is to measure the change in amyloid burden (defined as % change in ECV from baseline) over time in patients receiving eplontersen versus placebo. Methods Participants will undergo CMR with ECV mapping at baseline, 25, 49, 97 and 140 weeks (Figure 1). Images will be acquired under a standardized protocol comprising cine imaging with steady state free precession sequence, late gadolinium enhancement imaging (LGE) and T1 mapping. T1 mapping will be performed before the administration of contrast and will be repeated 15 minutes post-contrast using the same slice locations, to produce ECV maps. Results In the main study, 1432 patients were randomized from 120 sites across 20 countries. Of these patients, 157 patients were enrolled in the CMR sub-study, from 6 centers across 4 countries. Images will be read centrally at the end of the study. All participants in the study will also receive serial transthoracic echocardiography with strain analysis to correlate findings with conventional imaging techniques, and a subset of patients from the CMR substudy will be co-enrolled in a scintigraphy substudy for further characterization of amyloid deposition in their heart. Conclusion The CARDIO-TTRansform CMR substudy represents the largest CMR study of ATTR-CM. The CMR sub-study has enrolled a broad global population of patients with hereditary and wild-type ATTR-CM and will provide key information on the impact of eplontersen on the cardiac amyloid load and the associated change in structure and function.

Prognostic evaluation with cardiac magnetic resonance in patients with systemic sclerosis

Abstract Systemic sclerosis (SSc) is an autoimmune disease with multiorgan involvement. Cardiac involvement is common and impact in prognosis. Cardiac magnetic resonance (CMR) allows an evaluation in ventricular and atrial function and hemodynamics forces. Our study aimed to assess RVD prevalence in SSc patients and analyze its impact on cardiovascular events. Methods In this retrospective study, we included patients diagnosed with SSc and followed-up in a specialized unit. We collected clinical, hemodynamic, and imaging data, including baseline CMR studies. Pulmonary function tests were also performed. RVD was defined as a right ventricular ejection fraction ≤52% in men and ≤51% in women. Patients were monitored for a composite endpoint consisting of cardiovascular death and/or admissions due to heart failure (HF). We assessed the predictors of this endpoint using Cox regression analysis. Results The study included 74 patients with SSc, most were female (81 %) with a mean age of 60±12 years. RVD prevalence was 32 %. Patients with RVD had greater ventricular volumes (160±44.9 vs 130±36.2; p=0.003), lower right ventricular global strain (-18 % vs. -26 %; p <0.001) and lower right atria strain (19% vs 29%; p=<0.001). We don’t found differences in presence of LGE of both ventricles. In the multivariate analysis RVEF (HR 2.9.; p = 0.022), pulmonary trunk dilatation (HR 1.15; p= 0.004, pulmonary hypertension at baseline (HR 2.98; 0.09); RV GLS (HR 1.08; p = 0.03) and RA GLS (HR 0.96; p = 0.024) were predictors of composite outcome of cardiovascular death and/or heart failure hospitalization. During a mean follow-up of 46 months, patients with RVD had higher rates of heart failure admissions (38% vs. 12%; p = 0.01) and cardiovascular mortality (29% vs. 6%; p 0.01). No ventricular arrhythmias occurred. Conclusion RVD is common among SSc patients. RVEF and pulmonary hypertension are the strongest variables linked to increased adverse cardiovascular clinical events and decreased survival in these patients.

Deep learning of echocardiography distinguishes between presence and absence of late gadolinium enhancement on cardiac magnetic resonance in patients with hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) can cause myocardial fibrosis, which can be a substrate for fatal ventricular arrhythmias and subsequent sudden cardiac death. Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) represents myocardial fibrosis and is associated with sudden cardiac death in patients with HCM, CMR is resource-intensive, can carry an economic burden, and is sometimes contraindicated. In this study for patients with HCM, we aimed to distinguish between patients with positive and negative LGE on CMR using deep learning of echocardiographic images.MethodsIn the cross-sectional study of patients with HCM, we enrolled patients who underwent both echocardiography and CMR. The outcome was positive LGE on CMR. Among the 323 samples, we randomly selected 273 samples (training set) and employed deep convolutional neural network (DCNN) of echocardiographic 5-chamber view to discriminate positive LGE on CMR. We also developed a reference model using clinical parameters with significant differences between patients with positive and negative LGE. In the remaining 50 samples (test set), we compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the DCNN-derived probability and the reference model.ResultsAmong the 323 CMR studies, positive LGE was detected in 160 (50%). The reference model was constructed using the following 7 clinical parameters: family history of HCM, maximum left ventricular (LV) wall thickness, LV end-diastolic diameter, LV end-systolic volume, LV ejection fraction < 50%, left atrial diameter, and LV outflow tract pressure gradient at rest. The discriminant model combining the reference model with DCNN-derived probability significantly outperformed the reference model in the test set (AUC 0.86 [95% confidence interval 0.76–0.96] vs. 0.72 [0.57–0.86], P = 0.04). The sensitivity, specificity, positive predictive value, and negative predictive value of the combined model were 0.84, 0.76, 0.78, and 0.83, respectively.ConclusionCompared to the reference model solely based on clinical parameters, our new model integrating the reference model and deep learning-based analysis of echocardiographic images demonstrated superiority in distinguishing LGE on CMR in patients with HCM. The novel deep learning-based method can be used as an assistive technology to facilitate the decision-making process of performing CMR with gadolinium enhancement.

Feasibility of a Cardiac Magnetic Resonance Protocol for "off-on" Cardiac Resynchronization Therapy Evaluation.

Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure and electrical dyssynchrony. Cardiac magnetic resonance (CMR) is the gold standard for assessing left ventricular (LV) function. However, the feasibility of using CMR with active CRT is still uncertain. To assess the feasibility of a CRT "off-on" protocol during CMR and measure the acute effects of CRT interruption on LV function. Patients underwent CMR before (pre-CRT) and 6 months after (post-CRT) an MR-conditional CRT defibrillator implantation. The post-CRT scan included two complete sets of cine images, one with inactive (post-CRTOFF) and one with active CRT (post-CRTON), maintaining a continuous connection between device and programmer. Out of 29 enrolled patients, 8 (28%) had complete and analyzable post-CRT data. Unsuccessful procedures were attributed to connection problems between the CRT device and the programmer (n = 10), poor image quality (n = 7), and lack of patient cooperation (n = 4). LV ejection fraction significantly increased between pre-CRT scan (28.1%) and both post-CRTOFF (37.9%; p = 0.046) and post-CRTON CMR (35.0%; p = 0.037), with a nonstatistically significant trend toward decreased LV volumes. No adverse events or significant changes in device electrical parameters (including battery level) were detected during the post-CMR scan period. A CRT "off-on" protocol during CMR studies can be safely executed in patients with an MR-conditional CRT defibrillator. However, technical improvements are needed to facilitate high-quality scans during active CRT. Favorable changes in LV function induced by CRT remodeling were not acutely reversed with the interruption of electrical therapy.

Searching for genetic determinants for left ventricular non-compaction.

Left ventricular non-compaction (LVNC) is still a pathology around which there are numerous controversies regarding the criteria for its diagnosis, presentation, prognosis, and even classification into the appropriate group of diseases. So far, about 190 genes in which mutations may be associated with LVNC have been described, and in each of them, several to several dozen different loci have been discovered. We decided to analyze the frequency of single nucleotide variants (SNVs) in correlation to Petersen's criteria. We retrospectively analyzed the results of cardiac magnetic resonance (CMR) studies. Twenty-three patients who met Petersen's criteria agreed to participate in the research and take blood samples for genetic testing. Next, we prospectively included 24 volunteers who did not meet Petersen's criteria. Petersen's criteria were complied with ratio of non-compacted to compacted myocardium (NC/C) ≥2.3. A total of 47 DNA samples were analyzed based on the selected regions of the following genes: β-myosin heavy chain (MYH7), α-cardiac actin (ACTC1), cardiac troponin T (TNNT2), myosin binding protein-C (MYBPC3), LIM-domain binding protein 3 (LBD3), and taffazin (TAZ). In total, 248 substitutions in exons and introns were obtained for all analyzed samples. No statistically significant differences were detected between the mentioned groups. No significant difference in either downward or upward trends in the number of substitutions in relation to the increasing trabeculation is observed. We indicated differences in the occurrence of the studied SNVs between groups, especially for rs8037241 (3'UTR region of ACTC1) and rs2675686 (LDB3), but they also did not show statistical significance. Although we did not find a significant correlation between the co-occurrence of individual mutations with LVNC, it is worth noting that the presence of one of the four mutations in the range rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2e. 12), and rs727503240 (MYH7e. 39) increases the risk of LVNC more than 4 times. An inverse association between the number of SNVs and the meeting the Petersen's criteria was demonstrated for studied LDB3 region and rs397516254 in exon 39 of the MYH7 gene. To our knowledge, no studies have been published comparing the prevalence of selected SNVs in a group of healthy subjects and in a group meeting the Petersen criteria for LVNC. Among both completely healthy individuals who did not meet the Petersen criteria for LVNC as well as those with symptoms who met these criteria we found a similar incidence of SNVs in the ACTC1, TNNT2, LDB3 and MYH7 genes segments analyzed. Further studies are required to confirm or exclude "potentially protective" SNV in the 39th exon of MYH7 (rs397516254) and the role of co-occurrence of individual SNVs in rs8037241 (ACTC1 3'UTR), rs3729998 (TNNT2), and rs727503240 (MYH7) for the increase of the risk of LVNC.

The differential effects of dyslipidemia status and triglyceride-glucose index on left ventricular global function and myocardial microcirculation in diabetic individuals: a cardiac magnetic resonance study

BackgroundIt remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging.MethodsA total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI.ResultsThe LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (− 0.159[− 0.281, − 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (− 0.147[− 0.272, − 0.024], p = 0.02) and upslope (− 0.200[− 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023).ConclusionsBoth dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage.

Alteration of cardiac structure and function and its prognostic value in patients with Takayasu arteritis: a cardiac magnetic resonance study.

To investigate the prevalence and characteristics of late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) and its prognostic value in patients with Takayasu arteritis (TA). Sixty TA patients with a CMR examination were retrospectively included. All TA patients were divided into with LGE-positive and LGE-negative groups. Bi-ventricular function and location, distribution, and pattern of left ventricular (LV) LGE were evaluated in both LGE-positive and LGE-negative groups. Primary outcome was defined as a composite of cardiovascular death, hospitalization for heart failure, coronary artery revascularization, and stroke. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the association between variables and primary outcomes. Sixty consecutive TA patients were enrolled in this study. The mean age was 38.2 ± 13.8 years and 54 patients (54/60, 90.0%) were female. LGE-positive was observed in twenty-one (21/60, 35%) patients in the total patients with TA. LGE was predominantly distributed in the middle wall and subendocardial. The patchy and infarcted LGE patterns were the most common. Compared with the LGE-negative group, the LGE-positive group had reduced LV ejection fraction (P = 0.033), elevated LV end-diastolic volume index (P = 0.008), LV end-systolic volume index (P = 0.012), and LV mass (P = 0.008). During a median follow-up period of 1,892 days (interquartile range: 1,764-1,988 days), the primary outcomes occurred in thirteen patients. In the univariate analysis, LGE-positive (hazard ratio [HR] = 4.478, 95% confidence interval [CI]: 1.376-14.570; P = 0.013) were independently associated with the primary outcomes. However, LGE-positive did not retain its value as an independent predictor of primary outcomes in the multivariate analysis. Instead, LVMI (HR = 1.030, 95%CI: 1.013-1.048; P = 0.001) was the strongest independent predictor of primary outcomes in patients with TA. The Kaplan-Meier plot revealed that patients with LVMI ≥ 57.5 g/m2 have a worse prognosis. LGE-positive detected by CMR was observed in 35% of total TA patients with different distributions and patterns. LGE is associated with adverse LV remodeling and worsen cardiac function. However, LVMI rather than LGE can provide independent prognostic information in patients with TA.

Rationale and design of RESILIENCE: A prospective randomized clinical trial evaluating remote ischaemic conditioning for the prevention of anthracycline cardiotoxicity.

There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC. REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population. The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population.

Prognostic value of electroanatomic-guided endomyocardial biopsy in patients with myocarditis, arrhythmogenic cardiomyopathy and non dilated left ventricular cardiomyopathy

A wide variety of non-invasive and invasive techniques for SCD risk stratification in non ischemic cardiomyopathy (NICM) have been proposed, including left ventricular (LV) ejection fraction, QRS duration, late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and invasive electrophysiologic study with or without three-dimensional electroanatomic mapping (3D-EAM), to identify and characterize the arrhythmogenic substrate. There is still no clear consensus on the risk stratification in this clinical setting.The aim of our study is to characterize the 3D-EAM substrate in patients with the same clinical presentation of unexplained complex VAs and NICM using CMR, three-dimensional electranatomic mapping (3D-EAM) in association with endomyocardial biopsy (EMB) and genetic screening, as a more precise and early diagnostic assessment may provide important subsequent prognostic impact. The study was designed as a prospective multi-center observational evaluation and the patient follow-up was scheduled at 6 months interval. We enrolled 125 patients distinct into four different group by complete diagnostic work-up: myocarditis, non-dilated left ventricular cardiomyopathy, arrhythmogenic cardiomyopathy and control group. The four groups were compared in terms of clinical, imaging and 3D-EAM data. At multivariate analysis sustained VT/VF on admission [HR: 3.64 (1.79–7.4), p < 0.001], total bipolar scar area of left and right ventricle detected by 3D-EAM [HR: 2.24 (1.13–4.49), p = 0.02], histological diagnosis of myocarditis by 3D-EAM guided endomyocardial biopsy (EBM) [HR: 2.79 (1.04–7.44), p = 0.01] were independent predictors of complex VAs or death at follow-up. 3D-EAM guided EMB represent not only a valid diagnostic tool to identify the arrhythmogenic substrate in patients with NICM and ventricular arrhythmic phenotype but also an important predictor of complex Vas at long term follow-up.