Native Myocardial T1 Times Research Articles

Native hepatic T1-time as a non-invasive predictor of diastolic dysfunction and a monitoring tool for disease progression and treatment response in patients with pulmonary hypertension

AimsHepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). Methods and resultsWe retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. ConclusionsHepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.

Improvement in Cardiac Morphology Demonstrated by Cardiac Magnetic Resonance Imaging and Echocardiography after Haploidentical Hematopoietic Cell Transplantation in Adults with Sickle Cell Disease

Cardiopulmonary complications account for approximately 40% of deaths in patients with sickle cell disease (SCD). Diffuse myocardial fibrosis, elevated tricuspid regurgitant jet velocity (TRV) and iron overload are all associated with early mortality. While HLA-matched sibling hematopoietic cell transplant (HCT) offers a potential cure, fewer than 20% of patients have a suitable donor. Haploidentical HCT allows for an increased donor pool and has recently demonstrated improved safety and efficacy. Our group has reported improved cardiac morphology via echocardiography at one year after HCT. Herein, we describe the first use of cardiac magnetic resonance imaging (CMR), the gold standard for measuring volume, mass, and ventricular function, to evaluate changes in cardiac morphology post-HCT in adults with SCD. We analyzed baseline and 1-year data from 12 adults with SCD who received nonmyeloablative haploidentical peripheral blood HCT at the NIH. Patients underwent non-contrast CMR at 3T, echocardiography, and laboratory studies. One year after HCT, patients showed marked improvement in cardiac chamber morphology by CMR, including left ventricular (LV) mass and volume (70.2 to 60.1 g/m2, p = 0.02; 114.5 to 90.6 mL/m2, p = 0.001). Furthermore, mean TRV normalized by 1 year, suggesting that HCT may offer a survival benefit. Fewer patients had pathologically prolonged native myocardial T1 times, an indirect marker of myocardial fibrosis at 1 year; these data showed a trend toward significance. In this small sample, CMR was very sensitive in detecting cardiac mass and volume changes after HCT and provided complementary information to echocardiography. Notably, post-HCT improvement in cardiac parameters can be attributed only in part to the resolution of anemia; further studies are required to determine the role of myocardial fibrosis reversal, improved blood flow, and survival impact after HCT for SCD.

Genetics of myocardial interstitial fibrosis in the human heart and association with disease.

Myocardial interstitial fibrosis is associated with cardiovascular disease and adverse prognosis. Here, to investigate the biological pathways that underlie fibrosis in the human heart, we developed a machine learning model to measure native myocardial T1 time, a marker of myocardial fibrosis, in 41,505 UK Biobank participants who underwent cardiac magnetic resonance imaging. Greater T1 time was associated with diabetes mellitus, renal disease, aortic stenosis, cardiomyopathy, heart failure, atrial fibrillation, conduction disease and rheumatoid arthritis. Genome-wide association analysis identified 11 independent loci associated with T1 time. The identified loci implicated genes involved in glucose transport (SLC2A12), iron homeostasis (HFE, TMPRSS6), tissue repair (ADAMTSL1, VEGFC), oxidative stress (SOD2), cardiac hypertrophy (MYH7B) and calcium signaling (CAMK2D). Using a transforming growth factor β1-mediated cardiac fibroblast activation assay, we found that 9 of the 11 loci consisted of genes that exhibited temporal changes in expression or open chromatin conformation supporting their biological relevance to myofibroblast cell state acquisition. By harnessing machine learning to perform large-scale quantification of myocardial interstitial fibrosis using cardiac imaging, we validate associations between cardiac fibrosis and disease, and identify new biologically relevant pathways underlying fibrosis.

Cardiovascular magnetic resonance for early detection of late cardiotoxicity in asymptomatic survivors of hodgkin and non-hodgkin lymphoma

Abstract Funding Acknowledgements Type of funding sources: None. Background Long-term survivors of Hodgkin (HL) and non-Hodgkin (NHL) lymphomas experience late adverse effects of mediastinal radiotherapy and/or anthracycline containing chemotherapy, which lead to premature cardiovascular morbidity and mortality. It is unknown whether early stages of myocardial dysfunction and heart failure in these survivors can be detected by cardiovascular magnetic resonance imaging (CMR). Purpose To identify early sensitive markers for the detection of subclinical late cardiotoxicity using CMR in asymptomatic survivors of HL and (primary mediastinal large B-cell lymphoma) NHL. Methods For this prospective observational study, we included 80 HL or selected NHL survivors, who have been free of disease for ≥5 years and were treated with mediastinal radiotherapy (RT) with/without chemotherapy. Patients with known cardiac disease were excluded. Included patients were compared to 40 age- and sex matched healthy controls. CMR included 1) cine imaging for assessment of left ventricular (LV) and right ventricular (RV) dimensions, systolic function and strain; 2) 2-dimensional late gadolinium enhancement (LGE) imaging; 3) T2 mapping and 4) pre- and post-contrast T1 mapping (MOLLI) for assessment of native T1 values and extracellular volume (ECV). Results Of the 80 patients, 78 (98%) had a history of HL and 2 (2%) of NHL with a mean age of 47 ± 11 years (46% male). All patients were treated with mediastinal RT which was combined with anthracycline containing chemotherapy in 68 (85%) patients. The median interval between diagnosis and CMR was 20 [14 – 26] years. Differences in CMR characteristics between patients and healthy controls are shown in the table. LV end-systolic volume was statistically significantly higher, but LV ejection fraction and mass were significantly lower in patients compared to healthy controls. RV volumes were significantly lower in patients, but RV ejection fraction was preserved. Strain parameters of the LV, i.e. global longitudinal strain, global circumferential strain and global radial strain, were slightly but significantly reduced in patients. No significant differences were found in myocardial T2 times and ECV; however, native myocardial T1 time was significantly higher in patients compared to healthy controls. LGE was detected in 25% of the patients and in the majority of patients with LGE this was classified as hinge point fibrosis. Conclusion Asymptomatic survivors of HL and NHL are not exempt of late cardiotoxicity, which can be detected by subtle changes in LV myocardial function, strain and native T1 value with CMR. Furthermore, late gadolinium enhancement was present in 25% of the patients. Further longitudinal studies are needed to assess the implication of these changes in relation to clinical outcome.

Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal

BackgroundMapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping.MethodsThis is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2.ResultsTwenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (− 25 ml, p = 0.002), LV stroke volume (− 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (− 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters.ConclusionsAcute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.

Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study

ObjectivesA proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance. BackgroundCKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown. MethodsA total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T1 mapping (biomarker of diffuse fibrosis), T2 mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro–B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography. ResultsNative myocardial T1 times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/eʹ, N-terminal pro–B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VO2Peak, %VO2VT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T1 time (p < 0.001). Native myocardial T1 time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VO2Peak (p < 0.001). ConclusionsImaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862)

FASt single-breathhold 2D multislice myocardial T1 mapping (FAST1) at 1.5T for full left ventricular coverage in three breathholds.

BackgroundConventional myocardial T1 mapping techniques such as modified Look–Locker inversion recovery (MOLLI) generate one T1 map per breathhold. T1 mapping with full left ventricular coverage may be desirable when spatial T1 variations are expected. This would require multiple breathholds, increasing patient discomfort and prolonging scan time.PurposeTo develop and characterize a novel FASt single‐breathhold 2D multislice myocardial T1 mapping (FAST1) technique for full left ventricular coverage.Study TypeProspective.Population/PhantomNumerical simulation, agarose/NiCl2 phantom, 9 healthy volunteers, and 17 patients.Field Strength/Sequence1.5T/FAST1.AssessmentTwo FAST1 approaches, FAST1‐BS and FAST1‐IR, were characterized and compared with standard 5‐(3)‐3 MOLLI in terms of accuracy, precision/spatial variability, and repeatability.Statistical TestsKruskal‐Wallis, Wilcoxon signed rank tests, intraclass correlation coefficient analysis, analysis of variance, Student's t‐tests, Pearson correlation analysis, and Bland–Altman analysis.ResultsIn simulation/phantom, FAST1‐BS, FAST1‐IR, and MOLLI had an accuracy (expressed as T1 error) of 0.2%/4%, 6%/9%, and 4%/7%, respectively, while FAST1‐BS and FAST1‐IR had a precision penalty of 1.7/1.5 and 1.5/1.4 in comparison with MOLLI, respectively. In healthy volunteers, FAST1‐BS/FAST1‐IR/MOLLI led to different native myocardial T1 times (1016 ± 27 msec/952 ±22 msec/987 ± 23 msec, P < 0.0001) and spatial variability (66 ± 10 msec/57 ± 8 msec/46 ± 7 msec, P < 0.001). There were no statistically significant differences between all techniques for T1 repeatability (P = 0.18). In vivo native and postcontrast myocardial T1 times in both healthy volunteers and patients using FAST1‐BS/FAST1‐IR were highly correlated with MOLLI (Pearson correlation coefficient ≥0.93).Data ConclusionFAST1 enables myocardial T1 mapping with full left ventricular coverage in three separated breathholds. In comparison with MOLLI, FAST1 yield a 5‐fold increase of spatial coverage, limited penalty of T1 precision/spatial variability, no significant difference of T1 repeatability, and highly correlated T1 times. FAST1‐IR provides improved T1 precision/spatial variability but reduced accuracy when compared with FAST1‐BS. Level of Evidence: 1 Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2020;51:492–504.

Cardiac structure and function in patients with schizophrenia taking antipsychotic drugs: an MRI study

Cardiovascular disease (CVD) is a major cause of excess mortality in schizophrenia. Preclinical evidence shows antipsychotics can cause myocardial fibrosis and myocardial inflammation in murine models, but it is not known if this is the case in patients. We therefore set out to determine if there is evidence of cardiac fibrosis and/or inflammation using cardiac MRI in medicated patients with schizophrenia compared with matched healthy controls. Thirty-one participants (14 patients and 17 controls) underwent cardiac MRI assessing myocardial markers of fibrosis/inflammation, indexed by native myocardial T1 time, and cardiac structure (left ventricular (LV) mass) and function (left/right ventricular end-diastolic and end-systolic volumes, stroke volumes, and ejection fractions). Participants were physically fit, and matched for age, gender, smoking, blood pressure, BMI, HbA1c, ethnicity, and physical activity. Compared with controls, native myocardial T1 was significantly longer in patients with schizophrenia (effect size, d = 0.89; p = 0.02). Patients had significantly lower LV mass, and lower left/right ventricular end-diastolic and stroke volumes (effect sizes, d = 0.86–1.08; all p-values < 0.05). There were no significant differences in left/right end-systolic volumes and ejection fractions between groups (p > 0.05). These results suggest an early diffuse fibro-inflammatory myocardial process in patients that is independent of established CVD-risk factors and could contribute to the excess cardiovascular mortality associated with schizophrenia. Future studies are required to determine if this is due to antipsychotic treatment or is intrinsic to schizophrenia.

Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study

Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m2. Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ± 2% vs. 24 ± 2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ± 25 vs. 1002 ms ± 30, p = 0.014; ShMOLLI 974 ms ± 39 vs. 992 ms ± 33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ± 24 vs. 63 ± 20 ml/m2, p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ± 38 to 83 g/m2 ± 23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD.

Kidney transplantation is associated with reduced myocardial fibrosis. A cardiovascular magnetic resonance study with native T1 mapping

BackgroundThe measurement of native T1 through cardiovascular magnetic resonance (CMR) is a noninvasive method of assessing myocardial fibrosis without gadolinium contrast. No studies so far have evaluated native T1 after renal transplantation. The primary aim of the current study is to assess changes in the myocardium native T1 6 months after renal transplantation.MethodsWe prospectively evaluated 44 renal transplant patients with 3 T CMR exams: baseline at the beginning of transplantation and at 6 months after transplantation.ResultsThe native T1 time was measured in the midventricular septum and decreased significantly from 1331 ± 52 ms at the baseline to 1298 ± 42 ms 6 months after transplantation (p = 0.001). The patients were split into two groups through a two-step cluster algorithm: In cluster-1 (n = 30) the left ventricular (LV) mass index and the prevalence of diabetes were lower. In cluster-2 (n = 14) the LV mass index and diabetes prevalence were higher. Decrease in native T1 values was significant only in the patients in cluster-1 (p = 0.001).ConclusionsThe native myocardial T1 time decreased significantly 6 months after renal transplant, which may be associated with the regression of the reactive fibrosis. The patients with greater baseline LV mass index and the diabetic group did not reach a significant decrease in T1.

Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy.

AimsThis study aims to assess subclinical changes in functional and morphological myocardial magnetic resonance parameters very early into an anthracycline treatment, which may predict subsequent development of anthracycline‐induced cardiomyopathy (aCMP).Methods and resultsThirty sarcoma patients with planned anthracycline‐based chemotherapy (360–400 mg/m2 doxorubicin‐equivalent) were recruited. Median treatment time was 19.1 ± 2.1 weeks. Enrolled individuals received three cardiovascular magnetic resonance studies (before treatment, 48 h after first anthracycline treatment, and upon completion of treatment). Native T1 mapping (modified Look–Locker inversion recovery 5s(3s)3s), T2 mapping, and extracellular volume maps were acquired in addition to a conventional cardiovascular magnetic resonance with steady‐state free precession cine imaging at 1.5 T. Patients were given 0.2 mmol/kg gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10%. For analysis, 23 complete data sets were available. Nine patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. When assessed 48 h after first dose of antracyclines, patients with subsequent aCMP had significantly lower native myocardial T1 times compared with before therapy (1002.0 ± 37.9 vs. 956.5 ± 29.2 ms, P < 0.01) than patients who did not develop aCMP (990.9 ± 56.4 vs. 978.4 ± 57.4 ms, P > 0.05). Patients with aCMP had decreased left ventricular mass upon completion of therapy (86.9 ± 24.5 vs. 81.1 ± 22.3 g; P = 0.02), while patients without aCMP did not show a change in left ventricular mass (81.8 ± 21.0 vs. 79.2 ± 18.1 g; P > 0.05). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy.ConclusionsEarly decrease of T1 times 48 h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy.

Diffuse Myocardial Interstitial Fibrosis and Dysfunction in Early Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have a disproportionately high risk of cardiovascular (CV) morbidity and mortality from the very early stages of CKD. This excess risk is believed to be the result of myocardial disease commonly termed uremic cardiomyopathy (UC). It has been suggested that interstitial myocardial fibrosis progresses with advancing kidney disease and may be the key mediator of UC. This longitudinal study reports data on the myocardial structure and function of 30 patients with CKD with no known cardiovascular disease and healthy controls. All patients underwent cardiac magnetic resonance imaging including T1 mapping and late gadolinium enhancement (if estimated glomerular filtration rate > 30 ml/min/1.73 m2). Over a mean follow-up period of 2.7 ± 0.8 years, there was no change in left ventricular mass, volumes, ejection fraction, native myocardial T1 times, or extracellular volume with CKD or in healthy controls. Global longitudinal strain (20.6 ± 2.9 s−1 vs 19.8 ± 2.9 s−1, p = 0.03) and mitral annular planar systolic excursion (13 ± 2 mm vs 12 ± 2 mm, p = 0.009) decreased in CKD but were clinically insignificant. Midwall late gadolinium enhancement was present in 4 patients at baseline and was unchanged at follow-up. Renal function was stable in this cohort over follow-up (change in estimated glomerular filtration rate was −3 ml/min/1.73 m2) with no adverse clinical CV events. In conclusion, this study demonstrates that in a cohort of patients with stable CKD, left ventricular mass, native T1 times, and extracellular volume do not increase over a period of 2.7 years.

Increased myocardial native T1 relaxation time in patients with nonischemic dilated cardiomyopathy with complex ventricular arrhythmia.

To study the relationship between diffuse myocardial fibrosis and complex ventricular arrhythmias (ComVA) in patients with nonischemic dilated cardiomyopathy (NICM). We hypothesized that NICM patients with ComVA would have a higher native myocardial T1 time, suggesting more extensive myocardial diffuse fibrosis. We prospectively enrolled NICM patients with a history of ComVA (n = 50) and age-matched NICM patients without ComVA (n = 57). Imaging was performed at 1.5T with a protocol that included cine magnetic resonance imaging (MRI) for left ventricular (LV) function, late gadolinium enhancement (LGE) for focal scar, and native T1 mapping for diffuse fibrosis assessment. Global native T1 time was significantly higher in patients with NICM with ComVA when compared to patients with NICM without ComVA (1131 ± 42 vs. 1107 ± 45 msec, P = 0.006), and this finding remained after excluding segments with scar on LGE (1124 ± 36 vs. 1102 ± 44 msec, P = 0.006). Native T1 was similar in NICM patients with and without the presence of LGE (1121 ± 39 vs. 1117 ± 48 msec, P = 0.68) and mildly correlated with LV end-diastolic volume index (r = 0.27, P = 0.005), LV end-systolic volume index (r = 0.24, P = 0.01), and LV ejection fraction (r = -0.28, P = 0.003). Native T1 value for each 10-msec increment was an independent predictor of ComVA (odds ratio 1.14, 95% confidence interval 1.03-1.25; P = 0.008) beyond LV function and LGE. NICM patients with ComVA have higher native T1 compared to NICM without any documented ComVA. Native myocardial T1 is independently associated with ComVA, after adjusting for LV function and LGE. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:779-786. In memoriam: The authors are grateful for Dr. Josephson's inspiring guidance and contributions to this study.

Novel cardiac nuclear magnetic resonance method for noninvasive assessment of myocardial fibrosis in hemodialysis patients

Left ventricular hypertrophy and myocardial fibrosis frequently occur in patients with end-stage renal disease receiving hemodialysis therapy and are associated with poor prognosis. Native T1 mapping is a novel cardiac magnetic resonance imaging technique that measures native myocardial T1 relaxation, a surrogate of myocardial fibrosis. Here we compared global and segmental native myocardial T1 time and global longitudinal, circumferential and segmental strain, and cardiac function of 35 hemodialysis patients and 22 control individuals. The median native global T1 time was significantly higher in the hemodialysis than the control group (1270 vs. 1085 ms), with the septal regions of hemodialysis patients having significantly higher median T1 times than nonseptal regions (1293 vs. 1252 ms). The mean peak global circumferential strain and global longitudinal strain were both significantly reduced in hemodialysis patients compared with controls (-18.3 vs. -21.7 and -16.1 vs. -20.4, respectively). Systolic strain was also significantly reduced in the septum compared with the nonseptal myocardium in hemodialysis patients (-16.2 vs. -21.9) but not in control subjects. Global circumferential strain and longitudinal strain significantly correlated with global native T1 values (r= 0.41 and 0.55, respectively), and the septal native T1significantly correlated with the septal systolic strain (r= 0.46). Thus, myocardial fibrosis may be assessed noninvasively with native T1 mapping; the interventricular septum appears to be particularly prone to the development of fibrosis in hemodialysis patients.

Early-stage heart failure with preserved ejection fraction in the pig: a cardiovascular magnetic resonance study.

BackgroundThe hypertensive deoxy-corticosterone acetate (DOCA)-salt-treated pig (hereafter, DOCA pig) was recently introduced as large animal model for early-stage heart failure with preserved ejection fraction (HFpEF). The aim of the present study was to evaluate cardiovascular magnetic resonance (CMR) of DOCA pigs and weight-matched control pigs to characterize ventricular, atrial and myocardial structure and function of this phenotype model.MethodsFive anesthetized DOCA and seven control pigs underwent 3 T CMR at rest and during dobutamine stress. Left ventricular/atrial (LV/LA) function and myocardial mass (LVMM), strains and torsion were evaluated from (tagged) cine imaging. 4D phase-contrast measurements were used to assess blood flow and peak velocities, including transmitral early-diastolic (E) and myocardial tissue (E’) velocities and coronary sinus blood flow. Myocardial perfusion reserve was estimated from stress-to-rest time-averaged coronary sinus flow. Global native myocardial T1 times were derived from prototype modified Look-Locker inversion-recovery (MOLLI) short-axis T1 maps. After in-vivo measurements, transmural biopsies were collected for stereological evaluation including the volume fractions of interstitium (VV(int/LV)) and collagen (VV(coll/LV)). Rest, stress, and stress-to-rest differences of cardiac and myocardial parameters in DOCA and control animals were compared by t-test.ResultsIn DOCA pigs LVMM (p < 0.001) and LV wall-thickness (end-systole/end-diastole, p = 0.003/p = 0.007) were elevated. During stress, increase of LV ejection-fraction and decrease of end-systolic volume accounted for normal contractility reserves in DOCA and control pigs. Rest-to-stress differences of cardiac index (p = 0.040) and end-diastolic volume (p = 0.042) were documented. Maximal (p = 0.042) and minimal (p = 0.012) LA volumes in DOCA pigs were elevated at rest; total LA ejection-fraction decreased during stress (p = 0.006). E’ was lower in DOCA pigs, corresponding to higher E/E’ at rest (p = 0.013) and stress (p = 0.026). Myocardial perfusion reserve was reduced in DOCA pigs (p = 0.031). T1-times and VV(int/LV) did not differ between groups, whereas VV(coll/LV) levels were higher in DOCA pigs (p = 0.044).ConclusionsLA enlargement, E’ and E/E’ were the markers that showed the most pronounced differences between DOCA and control pigs at rest. Inadequate increase of myocardial perfusion reserve during stress might represent a metrics for early-stage HFpEF. Myocardial T1 mapping could not detect elevated levels of myocardial collagen in this model.Trial registrationThe study was approved by the local Bioethics Committee of Vienna, Austria (BMWF-66.010/0091-II/3b/2013).

Diffuse Interstitial Fibrosis and Myocardial Dysfunction in Early Chronic Kidney Disease

Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, it is hypothesized that nonatherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis, account for a significant excess of CV risk. This cross-sectional observational study of 129 age- (mean age 57±10 years) and gender-matched subjects examined: nondiabetic CKD stages 2 to 4 (mean glomerular filtration rate 50±22 ml/min/1.73 m2) with no history of CV disease, subjects who are hypertensive with normal renal function, and healthy controls. Cardiac magnetic resonance imaging was performed for assessment of LV volumes and systolic function (myocardial deformation). Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial T1 times before contrast and myocardial extracellular volume (ECV) after gadolinium administration in combination with standard late gadolinium enhancement techniques for detection of coarse fibrosis. Patients with CKD had increased native T1 times (986±37 ms) and ECV (0.28±0.04) compared with controls (955±30 ms, 0.25±0.03) and subjects who are hypertensive (956±31 ms, 0.25±0.02, p<0.05). Both T1 times and ECV were correlated with impaired systolic function as assessed by global longitudinal systolic strain (r=-0.22, p<0.05, and r=-0.43, p<0.01, respectively). There were no differences in LV volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is increased in early CKD and is associated with abnormal global longitudinal strain, an early feature of uremic cardiomyopathy and a key indicator of adverse CV prognosis.

Myocardial T1 mapping in pediatric and congenital heart disease.

In addition to the depiction of anatomy and function, tissue characterization of the myocardium has emerged as an important asset of cardiac magnetic resonance (CMR). Among the tissue properties that are quantifiable by CMR is diffuse myocardial fibrosis. Diffuse fibrosis is regarded to be the common pathological pathway toward loss of myocardial function in many cardiac conditions, including congenital heart disease.1–4 As fibrosis seems to have a major role in myocardial failure and may be reversible,5–8 its assessment by CMR has the potential to transform the way we monitor and treat our patients.9 In this review, we describe the technical aspects of fibrosis quantification with CMR and outline past and potential applications in congenital and pediatric heart disease. Diffuse myocardial fibrosis, which is present to a varying degree in children with acquired and congenital heart disease, has been attributed to abnormal loading conditions, cyanosis, and genetic predisposition.1,7,10,11 Myocardial fibrosis manifests in the pressure-loaded left ventricle of infants and children with aortic stenosis and coarctation.1 In patients with tetralogy of Fallot right ventricular myofiber disorganization and interstitial fibrosis have been demonstrated histologically.2,12 Interestingly, right ventricular fibrosis not only occurs in late adult survivors, but is already present in infants with this condition.12 The changes in myocardial architecture observed with fibrotic remodeling can be detrimental to heart function: Fibrous endocardial thickening of the right ventricular infundibulum is a predictor of poor right ventricular function in patients after tetralogy of Fallot repair.3 In patients with tricuspid atresia myocardial fibrosis is associated with systolic ventricular dysfunction early in life.4,13 In addition to being a mediator of cardiac dysfunction, diffuse fibrosis is the substrate for electric instability and a risk factor for life-threatening ventricular arrhythmia.14 Antifibrotic drugs have …

Free-breathing multislice native myocardial T1 mapping using the slice-interleaved T1 (STONE) sequence.

To develop a novel pulse sequence for free-breathing, multislice, native myocardial T1 mapping. The slice-interleaved T1 (STONE) sequence consists of multiple sets of single-shot images of different slices, acquired after a single nonselective inversion pulse. Each slice is only selectively excited once after each inversion pulse to allow sampling of the unperturbed longitudinal magnetization in the adjacent slices. For respiratory motion, a prospective slice-tracking respiratory navigator is used to decrease through-plane motion followed by a retrospective image registration to reduce in-plane motion. STONE T1 maps were calculated using both a two-parameter and three-parameter fit model. The accuracy and precision of the STONE sequence for different T1 , T2 , and inversion pulse efficiency were studied using numerical simulations and phantom experiments. T1 maps from 14 subjects were acquired with the STONE sequence and T1 s were compared to the MOdified Look-Locker Inversion recovery sequence (MOLLI). In numerical simulations and phantom experiments, the STONE sequence using a two-parameter fit model yields more accurate T1 times compared to MOLLI, with similar high precision. The three-parameter fit model further improves the accuracy, but with a reduced precision. The native myocardial T1 times were higher in the STONE sequence using two- or three-parameter fit compared to MOLLI. The standard deviation of the T1 times was lower in the STONE T1 maps with a two-parameter fit compared with MOLLI or a three-parameter fit. The STONE sequence allows accurate and precise quantification of native myocardial T1 times with the additional benefit of covering the entire ventricle. Magn Reson Med 74:115-124, 2015. © 2014 Wiley Periodicals, Inc.

In-vivo assessment of normal T1 values of the right-ventricular myocardium by cardiac MRI

To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33 ± 8 years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look-locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363 ± 37 ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42 ± 0.28 cm(2). In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p = 0.034). Average T1 time of the RV myocardium was 1,016 ± 61 ms, and average T1 of the left-ventricular (LV) was 956 ± 25 ms (p < 0.001). T1 mapping of the RV myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV.

Neurofibromatosis type 1 (NF1): knowledge, experience, and reproductive decisions of affected patients and families.

Eighty-one subjects (56 affected patients and 25 parents of isolated affected cases) from 63 families with neurofibromatosis type 1 (NF1) on the North Western Regional Genetic Family Register (NWRGFR) were interviewed. Patients were interviewed either before (n = 26) or after (n = 55) genetic counselling. In the group as a whole, knowledge of the clinical features and the genetic aspects of the condition was poor (mean score 7 within the range of 0 to 18). The following factors were significantly associated with higher knowledge: (1) genetic counselling, (2) higher social class, (3) child with NF1, (4) when NF1 had influenced reproductive decisions, (5) young age at diagnosis, and (6) member of a patient support group. The majority of the affected subjects perceived themselves to be more severely affected than by medical classification, with persons who had been diagnosed later in life, had a child with NF1, or who were concerned about the cosmetic aspects of the disease perceiving themselves to be more severely affected. Assessment of the psychosocial effects of NF1 at different stages of life showed that 63% of affected subjects experienced difficulties at school and 48% said that the condition, particularly cosmetic aspects, caused anxiety during adolescence (n = 54). These difficulties may have contributed to later problems with career attainment and confidence in relationships. Seventy-seven percent of parents stated that their child was experiencing difficulties at school relating to NF1 (n = 51). Of the subjects at risk of having a child with NF1 and who knew about NF1 before having their family (n = 32), 45% said that it had influenced their reproductive decisions. Of 29 subjects who were still considering children, 41% wished to have prenatal diagnosis in a future pregnancy, but only three subjects stated that they would terminate an affected pregnancy.