Multiparametric Cardiac Magnetic Resonance Research Articles

Characterisation of metabolic phenotype in aortic stenosis: insights from a multi-parametric cardiac magnetic resonance study

Abstract Introduction Left ventricular hypertrophy develops in Aortic stenosis (AS) as a result of increased afterload and is related to perturbations in cardiac fatty acid metabolism with evidence of steatosis and impaired myocardial energetics in severe AS. However, there is wide individual heterogeneity when it comes to degree of hypertrophy and progression to myocardial fibrosis and heart failure in those with same degree of stenosis. Underlying interplay of metabolism and hypertrophy may explain this variability. Purpose We sought to determine if a gradient of myocardial energetic impairment and steatosis exists across the spectrum of AS and precedes irreversible structural remodelling and subclinical LV dysfunction. We investigated metabolic remodelling in AS, focusing on its relationship with stenosis severity, degree of hypertrophy and fibrosis. Methods 74 AS participants including mild AS (n=18), asymptomatic moderate AS (n=38), asymptomatic severe AS (n=18), and healthy volunteers (n=13) underwent assessment of cardiac function, energetics (myocardial phosphocreatine to adenosine triphosphate ratio, PCr/ATP) and myocardial triglyceride content (MTG) using cardiovascular magnetic resonance (CMR) imaging and spectroscopy. Participants were divided into quartile groups based on their LV wall thickness (LVWT) and peak aortic valve gradient (AVG) to study relationship between cardiac metabolism and hemodynamic markers of LV structure and function. Results Baseline CMR characteristics (Fig. 1B-C) show a stepwise deterioration in LV structure and function across both the LVWT and AVG quartile groups (p values significant) with high LV mass index and relatively dilated LV as disease severity increases. Cardiac energetics (PCr/ATP]) were reduced in mild-moderate AS, Q2 (1.43±0.13 vs normal controls, Q1 1.80±0.14, p=0.05, Fig.2A) with a progressive decline with increasing AS severity (severe AS, Q4 PCr/ATP 1.39±0.14, p=0.02 vs controls). MTG was elevated in mild-moderate AS, Q2 (1.52±0.84 vs normal, Q1 1.25±0.70%, p=0.032, Fig. 2B). Whilst all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (R 0.219, p 0.03). In addition, PCr/ATP was strongly associated with the presence of myocardial fibrosis (p 0.01) strengthening the hypothesis that metabolic changes may play a causative role in disease progression (Fig. 2C). Conclusion A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, notably we show in our study that these metabolic changes precede irreversible LV remodelling and subclinical dysfunction. These findings may have value for defining distinct metabolic phenotypes and identifying those most at risk of decompensation. This also opens another avenue for precision metabolic therapy in AS with a potential to intervene and delay or prevent decompensation. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship

The value of CMR high-risk attributes in predicting ventricular remodeling in ST-segment-elevation myocardial infarction patients with mildly reduced or preserved ejection fraction

Objective: To evaluate the predictive value of a multiparametric cardiac magnetic resonance (CMR) approach for ventricular remodeling in ST-segment-elevation myocardial infarction (STEMI) patients with mildly reduced or preserved left ventricular ejection fraction (LVEF). Methods: This study is a prospective cohort study. STEMI patients with acute LVEF>40% after primary percutaneous coronary intervention (PCI) in Beijing Anzhen Hospital from October 2019 to September 2021 were enrolled. All patients received acute (3-7 days) and follow-up (3 months) CMR post-PCI. According to absence or presence of ventricular remodeling, patients were divided into ventricular remodeling group and non-ventricular remodeling group. Basic clinical characteristics and CMR indicators were analyzed and compared between the two groups. Logistic regression and receiver operating characteristic (ROC) curves were used to explore the predictive performance of CMR high-risk attributes for ventricular remodeling in STEMI patients with mildly reduced or preserved LVEF. The predictive value of combining multiple high-risk characteristics of CMR for ventricular remodeling was analyzed and compared with the traditional clinical risk factor model. Results: A total of 123 STEMI patients were enrolled (aged (57.1±11.1) years, 102 (82.9%) males). There were 97 cases (78.9%) patients in the non-ventricular remodeling group and 26 cases (21.1%) in the ventricular remodeling group. After adjustment for clinical risk factors, stroke volume<51.6 ml, global circumferential strain>-13.7%, infarct size>39.2%, microvascular obstruction>0.5%, and myocardial salvage index<43.9 were independently associated with ventricular remodeling in STEMI patients with mildly reduced or preserved LVEF. The incidence of ventricular remodeling increased with the increasing number of CMR high-risk attributes (P<0.01). The number of CMR high-risk attributes ≥3 was an independent predictor of adverse remodeling (adjusted OR=5.95, 95 CI%: 2.25-15.72, P<0.01) in STEMI patients with mildly reduced or preserved LVEF. Furthermore, the number of CMR high-risk attributes had incremental predictive value over baseline clinical risk factors (area under curve: 0.843 vs. 0.696, P<0.01). Conclusions: In STEMI patients with mild reduced or preserved LVEF, 5 CMR characteristics are associated with ventricular remodeling. The combination of ≥3 CMR high-risk characteristics is an independent predictor of ventricular remodeling, which has incremental predictive value beyond traditional risk factors in this patient cohort.

Using Multiparametric Cardiac Magnetic Resonance to Phenotype and Differentiate Biopsy-Proven Chronic from Healed Myocarditis and Dilated Cardiomyopathy.

(1) Objectives: To discriminate biopsy-proven myocarditis (chronic vs. healed myocarditis) and to differentiate from dilated cardiomyopathy (DCM) using cardiac magnetic resonance (CMR). (2) Methods: A total of 259 consecutive patients (age 51 ± 15 years; 28% female) who underwent both endomyocardial biopsy (EMB) and CMR in the years 2008–2021 were evaluated. According to right-ventricular EMB results, patients were divided into either chronic (n = 130, 50%) or healed lymphocytic myocarditis (n = 60, 23%) or DCM (n = 69, 27%). The CMR protocol included functional, strain, and late gadolinium enhancement (LGE) imaging, T2w imaging, and T2 mapping. (3) Results: Left-ventricular ejection fraction (LV-EF) was higher, and the indexed end-diastolic volume (EDV) was lower in myocarditis patients (chronic: 42%, median 96 mL/m²; healed: 49%, 86 mL/m²) compared to the DCM patients (31%, 120 mL/m²), p < 0.0001. Strain analysis demonstrated lower contractility in DCM patients vs. myocarditis patients, p < 0.0001. Myocarditis patients demonstrated a higher LGE prevalence (68% chronic; 59% healed) than the DCM patients (45%), p = 0.01. Chronic myocarditis patients showed a higher myocardial edema prevalence and ratio (59%, median 1.3) than healed myocarditis (23%, 1.3) and DCM patients (13%, 1.0), p < 0.0001. T2 mapping revealed elevated values more frequently in chronic (90%) than in healed (21%) myocarditis and DCM (23%), p < 0.0001. T2 mapping yielded an AUC of 0.89 (sensitivity 90%, specificity 76%) in the discrimination of chronic from healed myocarditis and an AUC of 0.92 (sensitivity 86%, specificity 91%) in the discrimination of chronic myocarditis from DCM, both p < 0.0001. (4) Conclusions: Multiparametric CMR imaging, including functional parameters, LGE and T2 mapping, may allow differentiation of chronic from healed myocarditis and DCM and therefore help to optimize patient management in this clinical setting.

Using multi-parametric quantitative MRI to screen for cardiac involvement in patients with idiopathic inflammatory myopathy

Idiopathic inflammatory myopathies (IIM) is a group of heterogeneous autoimmune systemic diseases, which not only involve skeletal muscle but also myocardium. Cardiac involvement in IIM, which eventually develops into heart failure, is difficult to identify by conventional examinations at early stage. The aim of this study was to investigate if multi-parametric cardiac magnetic resonance (CMR) imaging can screen for early cardiac involvement in IIM, compared with clinical score (Myositis Disease Activity Assessment Tool, MDAAT). Forty-nine patients of IIM, and 25 healthy control subjects with comparable age-range and sex-ratio were enrolled in this study. All subjects underwent CMR examination, and multi-slice short-axis and 4-chamber cine MRI were acquired to evaluate biventricular global circumferential strain (GCS) and global longitudinal strain (GLS). Native T1 and T2 mapping were performed, and post-contrast T1 mapping and LGE were acquired after administration of contrast. A CMR score was developed from native T1 mean and T2 mean for the identification of cardiac involvement in the IIM cohort. Using contingency tables MDAAT and CMR were compared and statistically analyzed using McNemar test. McNemar’s test revealed no significant difference between CMR score and MDAAT (p = 0.454). CMR score had potential to screen for early cardiac involvement in IIM patients, compared to MDAAT.

Left ventricular thrombus after acute ST-segment elevation myocardial infarction: multi-parametric cardiac magnetic resonance imaging with long-term outcomes.

Left ventricular thrombus (LVT) after acute ST-segment elevation myocardial infarction (STEMI) are generally associated with poorer outcomes for patients at long-term follow-up. We hypothesis that tissue characteristics and strain parameters by cardiac magnetic resonance (CMR) imaging may indicate the interactions of LVT with ventricular myocardium remodeling at both acute stage and chronic stages in STEMI patients. This retrospective study included 111 consecutive STEMI patients (38 with LVT and 73 without LVT). All patients underwent CMR during acute stage (within 7days) and chronic stage (after at least 2months) periods after percutaneous coronary intervention (PCI). Left ventricular native T1, extracellular volume (ECV), radial, circumferential, and longitudinal strain were analyzed in both phases. Major adverse cardiac events (MACE, including cardiovascular death, myocardial reinfarction, and hospitalization for heart failure), thromboembolic and bleeding events, were the clinical endpoints of the study. During the acute stage, left ventricular ejection fraction (LVEF) (OR 0.77, P value = 0.01) and longitudinal strain (OR 1.90, P value < 0.001) were correlated with LVT formation. Strain parameters were reduced, while the native T1 and ECV values of both the infarcted area and remote myocardium were elevated in LVT patients. During the chronic stage, LVT resolved in 29 of 38 patients (76%). LVT remaining patients had lower LVEF, a larger LV, and higher ECV in the acute stage than those of the LVT-resolved patients. In the long-term follow up of 678days, LVT (HR 2.45, P value = 0.02), aneurysm (HR 1.81, P value = 0.04), and native T1 (HR 2.44, P value = 0.01) were identified as three independent predictors of MACE, the incidence of thromboembolic events and bleeding events by a multivariable stepwise Cox proportional hazards regression. STEMI patients developing LVT had worse LV function, myocardial infarction extent, strain, and higher T1 and ECV values than STEMI patients without LVT. The LVT-remaining patients in the chronic stage had poorer functional and mapping parameters beginning in the first week. During the acute stage, LVEF and global longitudinal strain were independent correlated with LVT formation. During the long-term follow up, LVT, aneurysm and elevated myocardial T1 were associated with adverse outcomes in acute STEMI patients.

Time-dependent cardiac structural and functional changes after kidney transplantation: a multi-parametric cardiac magnetic resonance study.

To map time-dependent cardiac structural and functional change patterns after renal transplantation (KT) using cardiac magnetic resonance (CMR). Fifty-three patients with pre-KT and post-KT CMR exams were retrospectively analyzed. Patients were divided into three groups according to the time of post-KT CMR: group 1 (3 months post-KT, n = 16), group 2 (6 months post-KT, n = 21), and group 3 (over 9 months post-KT, n = 16). Twenty-one age- and sex-matched healthy controls (HC) were recruited for the study. CMR-derived left ventricular (LV) volumes, LV mass index (LVMi), LV ejection fraction (LVEF), global radial strain (GRS), global circumferential strain (GCS), global longitudinal strain (GLS), and native T1 value were compared. The association between the changes of CMR parameters was assessed. LVMi post-KT decreased in groups 2 (p < 0.001) and 3 (p = 0.004) but both groups had higher LVMi values compared to HC (both p < 0.001). GLS post-KT was decreased in group 1 (p = 0.021), but slightly increased in group 2 (p = 0.728) and group 3 (p = 0.100) without significant difference. GLS post-KT in group 3 was not different from HC (p = 0.104). LVEF, GRS, and GCS post-KT in groups 2 and 3 significantly increased and showed no significant difference from HC. The post-KT native T1 value in all three groups significantly decreased; however, no group showed any significant difference from HC. The change of LVEF was associated with the change of GCS, GRS, and GLS. Although GRS, GCS, GLS, and native T1 values reversed to normal level, LVMi remained impaired in median 14 months after KT. • Kidney transplantation has favorable effects on cardiac structure and function. • In a median 14 months of follow-up after KT, left ventricle strain and native T1 value reversed to normal level while LV mass index (LVMi) did not. Left ventricular hypertrophy may help to explain why KT recipients are still at increased cardiovascular risk. • The reason for the decrease of native T1 value after KT may be more than myocardial fibrosis and needs to be further studied.

Multiparametric Cardiac Magnetic Resonance Imaging Detects Altered Myocardial Tissue and Function in Heart Transplantation Recipients Monitored for Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a complication beyond the first-year post-heart transplantation (HTx). We aimed to test the utility of cardiac magnetic resonance (CMR) to detect functional/structural changes in HTx recipients with CAV. Seventy-seven prospectively recruited HTx recipients beyond the first-year post-HTx and 18 healthy controls underwent CMR, including cine imaging of ventricular function and T1- and T2-mapping to assess myocardial tissue changes. Data analysis included quantification of global cardiac function and regional T2, T1 and extracellular volume based on the 16-segment model. International Society for Heart and Lung Transplantation criteria was used to adjudicate CAV grade (0-3) based on coronary angiography. The majority of HTx recipients (73%) presented with CAV (1: n = 42, 2/3: n = 14, 0: n = 21). Global and segmental T2 (49.5 ± 3.4 ms vs 50.6 ± 3.4 ms, p < 0.001;16/16 segments) were significantly elevated in CAV-0 compared to controls. When comparing CAV-2/3 to CAV-1, global and segmental T2 were significantly increased (53.6 ± 3.2 ms vs. 50.6 ± 2.9 ms, p < 0.001; 16/16 segments) and left ventricular ejection fraction was significantly decreased (54 ± 9% vs. 59 ± 9%, p < 0.05). No global, structural, or functional differences were seen between CAV-0 and CAV-1. Transplanted hearts display functional and structural alteration compared to native hearts, even in those without evidence of macrovasculopathy (CAV-0). In addition, CMR tissue parameters were sensitive to changes in CAV-1 vs. 2/3 (mild vs. moderate/severe). Further studies are warranted to evaluate the diagnostic value of CMR for the detection and classification of CAV.

Differential Diagnosis of Thick Myocardium according to Histologic Features Revealed by Multiparametric Cardiac Magnetic Resonance Imaging.

Left ventricular (LV) wall thickening, or LV hypertrophy (LVH), is common and occurs in diverse conditions including hypertrophic cardiomyopathy (HCM), hypertensive heart disease, aortic valve stenosis, lysosomal storage disorders, cardiac amyloidosis, mitochondrial cardiomyopathy, sarcoidosis and athlete’s heart. Cardiac magnetic resonance (CMR) imaging provides various tissue contrasts and characteristics that reflect histological changes in the myocardium, such as cellular hypertrophy, cardiomyocyte disarray, interstitial fibrosis, extracellular accumulation of insoluble proteins, intracellular accumulation of fat, and intracellular vacuolar changes. Therefore, CMR imaging may be beneficial in establishing a differential diagnosis of LVH. Although various diseases share LV wall thickening as a common feature, the histologic changes that underscore each disease are distinct. This review focuses on CMR multiparametric myocardial analysis, which may provide clues for the differentiation of thickened myocardium based on the histologic features of HCM and its phenocopies.

Cardiac rest and stress metabolism in type 2 diabetes (T2D): can the diabetic heart flex under stress?

Abstract Background Efficient matching of energy supply to demand is essential for maintaining normal cardiac function. Altered cardiac metabolism may contribute to the development of cardiac dysfunction by impairing metabolic flexibility in type 2 diabetes (T2D). Purpose We aimed to evaluate the effect of T2D on myocardial substrate preferences in response to acute increases in cardiac workload and the effects on contractile function utilising simultaneous coronary sinus (CS) and aorta blood sampling and cardiac magnetic resonance (CMR) imaging Methods Eligible participants without obstructive coronary artery disease (&amp;gt;50% luminal coronary artery stenosis on coronary angiography) underwent transmyocardial arteriovenous blood sampling. Metabolites in paired coronary sinus and arterial samples were quantified to determine myocardial fuel selection at rest and during a stress protocol with intravenous dobutamine. Free fatty acid (FFA), glucose, 3-hydroxybutyric acid (3HBA) and lactate utilisation at rest and haemodynamic stress was calculated as an extraction fraction % (EF). Participants underwent dobutamine stress multiparametric CMR imaging at 3.0 Tesla (Skyra, Siemens, Germany) on a separate visit within 21 days to quantify cardiac volumes, function and perfusion. Results Two thousand and sixty-one participants were screened and due to stringent inclusion and exclusion criteria for this mechanistic study, three T2D patients and five matching controls were enrolled. Baseline demographics and metabolic and CMR results are documented in Table 1. At peak stress levels there was a significant increase in FFA use from rest to stress in controls only (p=0.002). There were no significant differences in FA or glucose uptake between T2D patients and controls at rest or stress. 3HBA EF was significantly increased in T2D during stress (25.04% vs 5.31%, p=0.007). Mean FFA and 3-HBA changes calculated as extraction fraction at stress and rest are illustrated in Figure 1. Conclusions We demonstrate for the first time in vivo that the diabetic heart switches to ketone bodies during increased workloads as a significant fuel source. At present, it is unknown whether enhanced ketone body metabolism in T2D is beneficial, maladaptive, or a bystander. As the energetic properties of ketones are favourable, increased myocardial ketone oxidation could be an adaptive change designed to compensate for defects in myocardial energy metabolism in diabetes. Further, larger studies are warranted. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation - Clinical Research Training FellowshipWellcome Trust Seed Grant Table 1Figure 1

Multiparametric Cardiovascular Magnetic Resonance in Acute Myocarditis: Comparison of 2009 and 2018 Lake Louise Criteria With Endomyocardial Biopsy Confirmation.

Background: Cardiac magnetic resonance (CMR) has been shown to improve the diagnosis of myocarditis, but no systematic comparison of this technique is currently available. The purpose of this study was to compare the 2009 and 2018 Lake Louise Criteria (LLC) for the diagnosis of acute myocarditis using 3.0 T MRI with endomyocardial biopsy (EMB) as a reference and to provide the cutoff values for multiparametric CMR techniques.Methods: A total of 73 patients (32 ± 14 years, 71.2% men) with clinically suspected myocarditis undergoing EMB and CMR with 3.0 T were enrolled in the study. Patients were divided into two groups according to EMB results (EMB-positive and -negative groups). The CMR protocol consisted of cine-SSFP, T2 STIR, T2 mapping, early and late gadolinium enhancement (EGE, LGE), and pre- and post-contrast T1 mapping. Their potential diagnostic ability was assessed with receiver operating characteristic curves.Results: The myocardial T1 and T2 relaxation times were significantly higher in the EMB-positive group than in the EMB-negative group. Optimal cutoff values were 1,228 ms for T1 relaxation times and 58.5 ms for T2 relaxation times with sensitivities of 86.0 and 83.7% and specificities of 93.3 and 93.3%, respectively. The 2018 LLC had a better diagnostic performance than the 2009 LLC in terms of sensitivity, specificity, positive predictive value, and negative predictive value. T1 mapping + T2 mapping had the largest area under the curve (0.95) compared to other single or combined parameters (2018 LLC: 0.91; 2009 LLC: 0.76; T2 ratio: 0.71; EGEr: 0.67; LGE: 0.73; ). The diagnostic accuracy for the 2018 LLC was the highest (91.8%), followed by T1 mapping (89.0%) and T2 mapping (87.7%).Conclusion: Emerging technologies such as T1/ T2 mapping have significantly improved the diagnostic performance of CMR for the diagnosis of acute myocarditis. The 2018 LLC provided the overall best diagnostic performance in acute myocarditis compared to other single standard CMR parameters or combined parameters. There was no significant gain when 2018LLC is combined with the EGE sequence.

Nicorandil Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats, as Evaluated by 7 T Cardiovascular Magnetic Resonance Imaging

PurposeDoxorubicin-induced cardiotoxicity (DIC) is a common side effect of doxorubicin chemotherapy, and a major mechanism of DIC is inflammation. However, no effective method exists to prevent DIC. In the present study, we investigated the cardioprotective effects of nicorandil against DIC using multiparametric cardiac magnetic resonance (CMR) imaging and elucidated the anti-inflammatory properties of nicorandil in rat models.MethodsMale Sprague-Dawley rats received four weekly intraperitoneal doxorubicin doses (4 mg/kg/injection) to establish the DIC model. After treatment with or without nicorandil (3 mg/kg/day) or diazoxide (10 mg/kg/day) orally, all the groups underwent weekly CMR examinations, including cardiac function and strain assessment and T2 mapping, for 6 weeks. Additionally, blood samples and hearts were collected to examine inflammation and histopathology.ResultsAccording to our results, the earliest DIC CMR parameter in the doxorubicin group was T2 mapping time prolongation compared with the DIC rats treated with nicorandil (doxorubicin+nicorandil group) at week 2. Subsequently, the left ventricular ejection fraction (LVEF) and global peak systolic myocardial strain in the doxorubicin group were significantly reduced, and nicorandil effectively inhibited these effects at week 6. Our results were confirmed by histopathological evaluations. Furthermore, nicorandil treatment had a protective effect against the doxorubicin-induced inflammatory response. Interestingly, similar protective results were obtained using the KATP channel opener diazoxide.ConclusionCollectively, our findings indicate that nicorandil application ameliorates DIC in rats with significantly higher cardiac function and myocardial strain and less fibrosis, apoptosis and inflammatory cytokine production. Nicorandil prevents T2 abnormalities in the early stages of DIC, showing a high clinical value for early nicorandil treatment in chemotherapy patients.

Multiparametric cardiac magnetic resonance imaging in pediatric and adolescent patients with acute myocarditis

BackgroundThe diagnostic value of cardiac magnetic resonance imaging (MRI) employing the 2018 Lake Louise criteria in pediatric and adolescent patients with acute myocarditis is undefined.ObjectiveTo evaluate the diagnostic value of the Lake Louise criteria in pediatric and adolescent patients with suspected acute myocarditis and to show the utility of cardiac MRI for follow-up in this patient cohort.Materials and methodsForty-three patients (age range: 8–21 years) with suspected acute myocarditis and 13 control patients who underwent cardiac MRI were retrospectively analyzed. T2-weighted and late gadolinium enhancement imaging were performed in all patients. T1 and T2 mapping were available in 26/43 patients (60%). The Lake Louise criteria were assessed. In 27/43 patients (63%), cardiac MRI follow-up was available. Receiver operating characteristic analysis, Pearson’s correlation coefficient and paired Student’s t-test were used for statistical analysis.ResultsIn the total cohort, the Lake Louise criteria achieved a sensitivity of 86% (95% confidence interval [CI]: 72–95%) and a specificity of 100% (95% CI: 79–100%) for the diagnosis of acute myocarditis. In the subgroup of patients with available mapping parameters, the diagnostic performance of the Lake Louise criteria was higher when mapping parameters were implemented into the score (area under the receiver operating characteristic curve: 0.944 vs. 0.870; P=0.033). T2 relaxation times were higher in patients with admission to the intermediate care unit and were associated with the length of intermediate care unit stay (r=0.879, P=0.049). Cardiac MRI markers of active inflammation decreased on follow-up examinations (e.g., T1 relaxation times: 1,032±39 ms vs. 975±33 ms, P<0.001; T2 relaxation times: 58±5 ms vs. 54±5 ms, P=0.003).ConclusionThe Lake Louise criteria have a high diagnostic performance for the diagnosis of acute myocarditis and are a valuable tool for follow-up in pediatric and adolescent patients. The mapping techniques enhance the diagnostic performance of the 2018 Lake Louise criteria.

Prognostic value of pulmonary transit time by cardiac magnetic resonance in patients with heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): National Institute for Health Research Leicester Cardiovascular Biomedical Research Centre Background Quantifying pulmonary transit time (PTT) from cardiac magnetic resonance (CMR) first pass perfusion imaging is a novel technique for the evaluation of haemodynamic congestion in heart failure. Previous studies have demonstrated that PTT is prolonged in patients with heart failure with reduced ejection fraction (HFrEF) and that it provides independent prognostic information in this patient group. However, the potential diagnostic and prognostic roles of PTT assessment in patients with heart failure with preserved ejection fraction (HFpEF) remain to be established. Aim To compare PTT in healthy controls and in patients with HFpEF, and to determine the prognostic value of PTT in HFpEF. Methods In a prospective, observational study, HFpEF and age-matched control subjects underwent multi-parametric CMR at 3-Tesla, comprising quantitative left ventricular volumetric assessment using a standard steady-state free precession (SSFP) pulse sequence, and first-pass perfusion imaging at rest using a T1-weighted segmented inversion recovery gradient echo sequence (following injection of 0.04mmol/kg of contrast). PTT was calculated as the time interval between the peaks of signal intensity curves in the right and left ventricular blood pools (defined on the basal slice of the rest perfusion images). The primary endpoint was the composite of death or hospitalisation with heart failure. Results 88 HFpEF patients (age 73 ± 9 years, 51% male, EF 56.4 ± 5.6%) and 40 controls (age 73 ± 5 years, 43% male, EF 58.5 ± 4.7%) were studied. PTT was comparable in HFpEF patients (7.7 ± 3.8s) and in healthy controls (7.5 ± 1.8, p = 0.69). Normalised to cardiac cycle lengths, PTT remained comparable in HFpEF patients and healthy controls (8.5 ± 4.0 cardiac cycles versus 7.8 ± 1.6 cardiac cycles, respectively, p = 0.19). In the HFpEF group, during median follow-up of 3.4 years, there were 38 events (25 hospitalisations with heart failure, 13 deaths); a significant relationship between survival and PTT was not demonstrated (HR 1.06 [0.99,1.14] for a one-unit increase, p = 0.098). Conclusion In HFpEF, PTT is not prolonged compared with PTT in healthy subjects. Unlike in HFrEF, PTT does not appear to be diagnostically or prognostically significant in HFpEF. Figure 1: Graph showing signal intensity curves in the right (red) and left (green) ventricular blood pools Figure 2: Kaplan-Meier plot showing comparable rates of the composite endpoint in patients with PTT greater/less than median PTT (8 cardiac cycles)

Left ventricular fibrosis and hypertrophy are associated with mortality in heart failure with preserved ejection fraction

Cardiac magnetic resonance (CMR) is emerging as an important tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This study sought to investigate the prognostic value of multiparametric CMR, including left and right heart volumetric assessment, native T1-mapping and LGE in HFpEF. In this retrospective study, we identified patients with HFpEF who have undergone CMR. CMR protocol included: cines, native T1-mapping and late gadolinium enhancement (LGE). The mean follow-up period was 3.2 ± 2.4 years. We identified 86 patients with HFpEF who had CMR. Of the 86 patients (85% hypertensive; 61% males; 14% cardiac amyloidosis), 27 (31%) patients died during the follow up period. From all the CMR metrics, LV mass (area under curve [AUC] 0.66, SE 0.07, 95% CI 0.54–0.76, p = 0.02), LGE fibrosis (AUC 0.59, SE 0.15, 95% CI 0.41–0.75, p = 0.03) and native T1-values (AUC 0.76, SE 0.09, 95% CI 0.58–0.88, p < 0.01) were the strongest predictors of all-cause mortality. The optimum thresholds for these were: LV mass > 133.24 g (hazard ratio [HR] 1.58, 95% CI 1.1–2.2, p < 0.01); LGE-fibrosis > 34.86% (HR 1.77, 95% CI 1.1–2.8, p = 0.01) and native T1 > 1056.42 ms (HR 2.36, 95% CI 0.9–6.4, p = 0.07). In multivariate cox regression, CMR score model comprising these three variables independently predicted mortality in HFpEF when compared to NTproBNP (HR 4 vs HR 1.65). In non-amyloid HFpEF cases, only native T1 > 1056.42 ms demonstrated higher mortality (AUC 0.833, p < 0.01). In patients with HFpEF, multiparametric CMR aids prognostication. Our results show that left ventricular fibrosis and hypertrophy quantified by CMR are associated with all-cause mortality in patients with HFpEF.

Invasive and non-invasive quantification of myocardial fibrosis in primary mitral regurgitation: prognostic implications for post-operative remodelling, symptom burden and exercise capacity

Abstract Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4 years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were feasible from 86 patients with median CVF of 14.6% [IQR 7.4–20.3]. Fibrosis was present even in NYHA Class I patients (13.6% [6.3–18.8]), and was significantly higher than the 3.3% [2.6–6.1] obtained from 8 autopsy controls without cardiac disease (P&amp;lt;0.001). Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although it did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV (27.4±3.3%) correlated with systolic (LVEF Rho=−0.22, P=0.029; LVESVi Rho=0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e' R=0.25, P=0.022), exercise capacity (%VO2max R=−0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Post-operatively, although LVEF remained normal (defined as &amp;gt;50%) in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P&amp;lt;0.001), there was a reduction in ECV (27.4±3.3 vs 26.6±2.8%, P=0.027) that was proportionate to its pre-operative expansion (Figure1), suggesting that fibrosis was reversible within our patients. Neither histological CVF nor ECV predicted change in LVESVi, LVEF, symptom burden or exercise capacity following repair. GCS was an independent predictor of post-operative LVESVi and LVEF on multiple linear regression models. Whilst improvements in symptom burden and exercise capacity was observed in NYHA II-III patients, this sub-group of patients failed to achieve the same level of fitness and symptom-free status as NYHA I patients (VO2max 92.2±18.8% vs 102.9±21.1%, P=0.017; MLHFQ 12 [5–26] vs 3 [0–10], P&amp;lt;0.001). Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Effects of Levosimendan on cardiac function, size and strain in heart failure patients

Levosimendan improves cardiac function in heart failure populations; however, its exact mechanism is not well defined. We analysed the short-term impact of levosimendan in heart failure patients with ischemic and non-ischemic cardiomyopathy (CMP) using multiparametric cardiac magnetic resonance (CMR). We identified 33 patients with ischemic or non-ischemic CMP who received two consecutive CMR scans prior to and within one week after levosimendan administration. Changes in LV ejection fraction (LVEF) and LV volumes, as well as changes in strain rates, were measured prior to and within one week after levosimendan infusion. LV scarring, based on late gadolinium enhancement (LGE), was correlated to changes in LV size and strain rates. Both LV endiastolic (EDV) and endsystolic volumes (ESV) significantly decreased (EDV: p=0,001; ESV: p=0,002) after levosimendan administration, with no significant impact on LVEF (p=0.41), cardiac output (p=0.61), and strain rates. Subgroup analyses of ischemic or non-ischemic CMP showed no significant differences between the groups in terms of short-term LV reverse remodeling. The presence and extent of scarring in LGE did not correlate with changes in LV size and strain rates. CMR is able to monitor cardiac effects of levosimendan infusion. Short-term follow-up of a single levosimendan infusion using CMR shows a significant decrease in LV size, but no impact on LVEF or strain measurements. There was no difference between patients with ischemic or non-ischemic CMP. Quantification of LV scarring in CMR is not able to predict changes in LV size and strain rates in response to levosimendan.

Additive effect of hypertension on left ventricular structure and function in patients with asymptomatic type 2 diabetes mellitus.

We aimed to comprehensively determine the effects of hypertension on left ventricular (LV) structure, microcirculation, tissue characteristics, and deformation in type 2 diabetes mellitus (T2DM) using multiparametric cardiac magnetic resonance (CMR) imaging. We prospectively enrolled 138 asymptomatic patients with T2DM (80 normotensive and 58 hypertensive individuals) and 42 normal glucose-tolerant and normotensive controls and performed multiparametric CMR examination to assess cardiac geometry, microvascular perfusion, extracellular volume (ECV), and strain. Univariable and multivariable linear analysis was performed to analyze the effect of hypertension on LV deformation in patients with T2DM. Compared with controls, patients with T2DM exhibited decreased strain, decreased microvascular perfusion, increased LV remodeling index, and increased ECV. Hypertension lead to greater deterioration of LV strain (peak strain-radial, P = 0.002; peak strain-longitudinal, P = 0.006) and LV remodeling index (P = 0.005) in patients with T2DM after adjustment for covariates; however, it did not affect microvascular perfusion (perfusion index, P = 0.469) and ECV (P = 0.375). In multivariable analysis, hypertension and diabetes were independent predictors of reduced LV strain, whereas hypertension is associated with greater impairment of diastolic function (P = 0.009) but not systolic function (P = 0.125) in the context of diabetes, independent of clinical factors and myocardial disorder. Hypertension in the context of diabetes is significantly associated with LV diastolic function and concentric remodeling; however, it has little effect on systolic function, myocardial microcirculation, or fibrosis independent of covariates, which provide clinical evidence for understanding the pathogenesis of comorbidities and explaining the development of distinct heart failure phenotypes.

Feature tracking and mapping analysis of myocardial response to improved perfusion reserve in patients with refractory angina treated by coronary sinus Reducer implantation: a CMR study.

Coronary sinus (CS) Reducer implantation improves myocardial perfusion and symptoms in patients with debilitating refractory angina. Its impact on myocardial remodeling remain uncertain. Aim of the present study was to assess possible impact of CS Reducer on myocardial systolic-diastolic deformation and microstructural remodeling, as assessed through cardiac magnetic resonance (CMR) feature tracking and mapping analysis. Twenty-eight consecutive patients with refractory angina underwent multiparametric stress CMR before and 4months after CS Reducer implantation. Eight patients were excluded (6 for absence of inducible ischemia, 2 for artifacts). Modifications in 3D systo-diastolic myocardial deformation were evaluated using feature tracking analysis on rest cine images. Myocardial microstructural remodeling was assessed by native T1 mapping, cellular and matrix volume and extracellular volume fraction (ECV). Collaterally, the percentage of ischemic myocardium (ischemic burden %) and the myocardial perfusion reserve index (MPRI) were measured. After CS Reducer implantation, myocardial contractility improved (ejection fraction rose from 61 to 67%; p = 0.0079), along with longitudinal (from - 16 to - 19%; p = 0.0192) and circumferential strain (from - 18 to - 21%; p = 0.0017). Peak diastolic radial, circumferential and longitudinal strain rate did not change (p > 0.05), and no changes in native T1, ECV, cellular and matrix volume were observed. Myocardial perfusion improved, with a reduction of ischemic burden (13-11%; p = 0.0135), and recovery of intramural perfusion balance in segments with baseline ischemia (MPRi endocardial/epicardial ratio from 0.67 to 0.96; p = 0.0107). CS Reducer improves myocardial longitudinal and circumferential strain, without microstructural remodeling and no impact on diastolic proprieties.

The combined effects of cardiac geometry, microcirculation, and tissue characteristics on cardiac systolic and diastolic function in subclinical diabetes mellitus-related cardiomyopathy

BackgroundDiabetes mellitus-related cardiomyopathy has recently been described as a distinct progression of left ventricular (LV) systolic and diastolic dysfunction. Pathological changes in the myocardium may explain the development of two different phenotypes. We evaluated the effects of LV geometry, myocardial microcirculation, and tissue characteristics on cardiac deformation in patients with subclinical type 2 diabetes mellitus (T2DM) utilizing multiparametric cardiac magnetic resonance (CMR) imaging. MethodsA total of 135 T2DM patients and 55 matched controls were prospectively enrolled and performed multiparametric CMR examination. CMR-derived parameters including cardiac geometry, function, microvascular perfusion, T1 mapping, T2 mapping, and strain were analyzed and compared between T2DM patients and controls. ResultsThe univariable and multivariable analysis of systolic and diastolic function revealed that longer duration of diabetes was associated with decreased longitudinal peak systolic strain rate (PSSR-L) (β = 0.195, p = .013), and higher remodeling index and higher extracellular volume (ECV) tended to correlate with decreased longitudinal peak diastolic strain rate (PDSR-L) (remodeling index, β = −0.339, p = .000; ECV, β = −0.172, p = .026), whereas microvascular perfusion index and T2 value affected both PSSR-L (perfusion index, β = −0.328, p = .000; T2 value, β = 0.306, p = .000) and PDSR-L (perfusion index, β = 0.209, p = .004; T2 value, β = −0.275, p = .000) simultaneously. ConclusionsThe LV concentric remodeling and myocardial fibrosis correlated with diastolic function, and perfusion function and myocardial edema were associated with both LV systolic and diastolic function.

Multiparametric cardiac magnetic resonance imaging of the heart in people with spinal cord injury

Cardiovascular disease is the foremost cause of death for individuals with spinal cord injuries and is a patient priority in this population. To reduce cardiovascular disease, health care costs, and address key patient‐centered priorities, we must understand how and why heart health deteriorates after high‐level spinal cord injuries. Using high‐resolution cardiac magnetic resonance imaging and analysis approaches (ie., 4D strain analysis, 4D flow imaging, late gadolinium enhancement), our objective was to evaluate the impact of high‐level spinal cord injury on cardiac structure and function. Cardiac dimensions including chamber wall thickness were reduced in people with cervical spinal cord injury compared to matched controls and fibrosis was more apparent. Furthermore, we observed changes in global markers of strain in the heart including both longitudinal and circumferential strain after spinal cord injury. Cardiac magnetic resonance imaging revealed deficits in structure and function of the left ventricle after SCI. The next steps are to establish the risk factors leading to abnormal hearts after spinal cord injury, and develop strategies for prevention and treatment.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Stephenson Cardiac Imaging Centre, University of Calgary, Libin Cardiovascular Institute, Hotchkiss Brain Institute, Campus Alberta Neuroscience, Clinical Neurosciences Pilot Research Fund Program, Compute Canada, Rick Hansen Institute, Wings for Life Foundation