Sex-Related Differences in the Extent of Myocardial Fibrosis in Patients With Aortic Valve Stenosis

ObjectivesThe aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS).BackgroundPrevious studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS.MethodsA total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis.ResultsThere was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th to 75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th to 75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th–75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th–75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05).ConclusionsWomen have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload.     

Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

ObjectivesThis study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.MethodsA total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.ResultsAt the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m², maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006).ConclusionsMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.     

Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging

ObjectivesThis study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).BackgroundMyocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.MethodsTwenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post–COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.ResultsFifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings. Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs. 38.1 ms ± 2.4 vs. 39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs. 24.8% [23.1% to 25.4%] vs. 23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).ConclusionsCardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.     

Pericardial Fat and the Risk of Heart Failure

BackgroundObesity is a well-established risk factor for heart failure (HF). However, implications of pericardial fat on incident HF is unclear.ObjectivesThis study sought to examine the association between pericardial fat volume (PFV) and newly diagnosed HF.MethodsThis study ascertained PFV using cardiac computed tomography in 6,785 participants (3,584 women and 3,201 men) without pre-existing cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards regression was used to evaluate PFV as continuous and dichotomous variable, maximizing the J-statistic: (Sensitivity + Specificity – 1).ResultsIn 90,686 person-years (median: 15.7 years; interquartile range: 11.7 to 16.5 years), 385 participants (5.7%; 164 women and 221 men) developed newly diagnosed HF. PFV was lower in women than in men (69 ± 33 cm³ vs. 92 ± 47 cm³; p < 0.001). In multivariable analyses, every 1-SD (42 cm³) increase in PFV was associated with a higher risk of HF in women (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.21 to 1.71; p < 0.001) than in men (HR: 1.13; 95% CI: 1.01 to 1.27; p = 0.03) (interaction p = 0.01). High PFV (≥70 cm³ in women; ≥120 cm³ in men) conferred a 2-fold greater risk of HF in women (HR: 2.06; 95% CI: 1.48 to 2.87; p < 0.001) and a 53% higher risk in men (HR: 1.53; 95% CI: 1.13 to 2.07; p = 0.006). In sex-stratified analyses, greater risk of HF remained robust with additional adjustment for anthropometric indicators of obesity (p ≤ 0.008), abdominal subcutaneous or visceral fat (p ≤ 0.03) or biomarkers of inflammation and hemodynamic stress (p < 0.001) and was similar among Whites, Blacks, Hispanics, and Chinese (interaction p = 0.24). Elevated PFV predominantly augmented the risk of HF with preserved ejection fraction (p < 0.001) rather than reduced ejection fraction (p = 0.31).ConclusionsIn this large, community-based, ethnically diverse, prospective cohort study, pericardial fat was associated with an increased risk of HF, particularly HF with preserved ejection fraction, in women and men.     

Prognostic Value of Myocardial Extracellular Volume Fraction and T2-mapping in Heart Transplant Patients

ObjectivesThe purpose of this study was to examine prognostic value of T1- and T2-mapping techniques in heart transplant patients.BackgroundMyocardial characterization using T2 mapping (evaluation of edema/inflammation) and pre- and post-gadolinium contrast T1 mapping (calculation of extracellular volume fraction [ECV] for assessment of interstitial expansion/fibrosis) are emerging modalities that have been investigated in various cardiomyopathies.MethodsA total of 99 heart transplant patients underwent the magnetic resonance imaging (MRI) scans including T1- (n = 90) and T2-mapping (n = 79) techniques. Relevant clinical characteristics, MRI parameters including late gadolinium enhancement (LGE), and invasive hemodynamics were collected. Median clinical follow-up duration after the baseline scan was 2.4 to 3.5 years. Clinical outcomes include cardiac events (cardiac death, myocardial infarction, coronary revascularization, and heart failure hospitalization), noncardiac death and noncardiac hospitalization.ResultsOverall, the global native T1, postcontrast T1, ECV, and T2 were 1,030 ± 56 ms, 458 ± 84 ms, 27 ± 4% and 50 ± 4 ms, respectively. Top-tercile-range ECV (ECV >29%) independently predicted adverse clinical outcomes compared with bottom-tercile-range ECV (ECV <25%) (hazard ratio [HR]: 2.87; 95% confidence interval [CI]: 1.07 to 7.68; p = 0.04) in a multivariable model with left ventricular end-systolic volume and LGE. Higher T2 (T2 ≥50.2 ms) independently predicted adverse clinical outcomes (HR: 3.01; 95% CI: 1.39 to 6.54; p = 0.005) after adjustment for left ventricular ejection fraction, left ventricular end-systolic volume, and LGE. Additionally, higher T2 (T2 ≥50.2 ms) also independently predicted cardiac events (HR: 4.92; CI: 1.60 to 15.14; p = 0.005) in a multivariable model with left ventricular ejection fraction.ConclusionsMRI-derived myocardial ECV and T2 mapping in heart transplant patients were independently associated with cardiac and noncardiac outcomes. Our findings highlight the need for larger prospective studies.     

Prognostic Value of Stress CMR Perfusion Imaging in Patients With Reduced Left Ventricular Function

ObjectivesThe aim of this study was to investigate the prognostic value of stress cardiac magnetic resonance imaging (CMR) in patients with reduced left ventricular (LV) systolic function.BackgroundPatients with ischemic cardiomyopathy are at risk from both myocardial ischemia and heart failure. Invasive testing is often used as the first-line investigation, and there is limited evidence as to whether stress testing can effectively provide risk stratification.MethodsIn this substudy of a multicenter registry from 13 U.S. centers, patients with reduced LV ejection fraction (<50%), referred for stress CMR for suspected myocardial ischemia, were included. The primary outcome was cardiovascular death or nonfatal myocardial infarction. The secondary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina or congestive heart failure, and unplanned late coronary artery bypass graft surgery.ResultsAmong 582 patients (mean age 62 ± 12 years, 34% women), 40% had a history of congestive heart failure, and the median LV ejection fraction was 39% (interquartile range: 28% to 45%). At median follow-up of 5.0 years, 97 patients had experienced the primary outcome, and 182 patients had experienced the secondary outcome. Patients with no CMR evidence of ischemia or late gadolinium enhancement (LGE) experienced an annual primary outcome event rate of 1.1%. The presence of ischemia, LGE, or both was associated with higher event rates. In a multivariate model adjusted for clinical covariates, ischemia and LGE were independent predictors of the primary (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.68 to 4.14; p < 0.001; and HR: 1.86; 95% CI: 1.05 to 3.29; p = 0.03) and secondary (HR: 2.14; 95% CI: 1.55 to 2.95; p < 0.001; and HR 1.70; 95% CI: 1.16 to 2.49; p = 0.007) outcomes. The addition of ischemia and LGE led to improved model discrimination for the primary outcome (change in C statistic from 0.715 to 0.765; p = 0.02). The presence and extent of ischemia were associated with higher rates of use of downstream coronary angiography, revascularization, and cost of care spent on ischemia testing.ConclusionsStress CMR was effective in risk-stratifying patients with reduced LV ejection fractions. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891)     

Left Ventricular Hypertrophy and Clinical Outcomes Over 5 Years After TAVR: An Analysis of the PARTNER Trials and Registries

ObjectivesThis study sought to evaluate the association between severity of left ventricular hypertrophy (LVH) before transcatheter aortic valve replacement (TAVR) and outcomes out to 5 years.BackgroundPrior studies assessing the association between baseline LVH and outcomes after surgical or TAVR for aortic stenosis (AS) have yielded conflicting results.MethodsPatients with severe symptomatic AS at intermediate or high risk in the PARTNER (Placement of Aortic Transcatheter Valve) 1, 2, and S3 trials and registries who received TAVR and had baseline measurements for left ventricular mass index (LVMi) were analyzed. The presence and severity of LVH was determined by LVMi using American Society of Echocardiography sex-specific cutoffs.ResultsAmong 4,280 patients, those with no (n = 1,325), mild (n = 777), moderate (n = 628), and severe (n = 1,550) LVH had 5-year rates of death of 32.8%, 37.3%, 37.2%, and 44.8%, respectively (p < 0.001), and 5-year rates of cardiovascular (CV) death or rehospitalization of 33.6%, 39.2%, 42.4%, and 49.2%, respectively (p < 0.001). After adjustment, severe LVH (compared with no LVH) was associated with increased all-cause death (adjusted hazard ratio: 1.16; 95% confidence interval: 1.00 to 1.34; p = 0.04) and CV death or rehospitalization (adjusted hazard ratio: 1.34; 95% confidence interval: 1.16 to 1.54; p < 0.001), but no increased hazard was observed for mild or moderate LVH. In spline analyses performed in males and females separately, there was a consistent linear association between increased LVMi and an increased adjusted hazard of CV mortality or rehospitalization. A similar relationship was observed for all-cause death in females, but not males.ConclusionsSevere baseline LVH is associated with higher 5-year death and rehospitalization rates after TAVR. These findings may have implications for the optimal timing of valve replacement and the potential role for medical therapy to slow or prevent LVH as AS progresses before valve replacement, but further studies are needed.     

Myocardial Fibrosis and Inflammation by CMR Predict Cardiovascular Outcome in People Living With HIV

ObjectivesThe goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).BackgroundPLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.MethodsThis prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).ResultsA total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m² [49 to 77 g/m²] vs. 57 g/m² [49 to 64 g/m²]), and N-terminal pro–B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events.ConclusionsOur findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).     

Comparing CMR Mapping Methods and Myocardial Patterns Toward Heart Failure Outcomes in Nonischemic Dilated Cardiomyopathy

ObjectivesIn patients with nonischemic dilated cardiomyopathy (NIDCM), native T1, partition coefficient (λ_Gd), and extracellular volume fraction (ECV) mapping may offer prognostic values beyond late gadolinium enhancement (LGE), by scaling the range of myocardial changes.BackgroundIn patients with NIDCM, LGE is seen in 30% of patients and it indicates adverse prognosis.MethodsThe study mapped 6 anatomical locations using all 4 cardiac magnetic resonance (CMR) tissue-characterizing methods and associated with outcome. The authors performed T1 mapping of the myocardium and the blood pool, before and serially after contrast injection, using a Look-Locker cine gradient-echo technique to obtain T1 and the corresponding reciprocal R1 values. λ_Gd values were derived from the slopes of the least-squares regression lines for myocardial versus blood R1, then adjusted to serum hematocrit to yield ECV.ResultsConsecutive 240 NIDCM patients (49 ± 16 years of age; 38% women) underwent CMR for cardiac function, LGE, native T1, λ_Gd, and ECV. After a median of 3.8 years, 36 (15%) experienced major adverse cardiac events (MACE), including 22 heart failure hospitalizations and 14 deaths. Nonischemic LGE was detected in 34%, whereas ECV was elevated (≥1 location) in 58%. Comparing the 4 methods, mean ECV and λ_Gd both demonstrated strong association with MACE (both p < 0.001). In contrast to native T1 and LGE, ECV values from all 6 locations were associated with MACE and death, with the anteroseptum being the most significant (p < 0.0001). The number of abnormal ECV locations correlated linearly with annual MACE rates (p = 0.0003). Mean ECV was the only predictor to enter a prognostic model that contained age, sex, New York Heart Association functional class, and left ventricular ejection fraction. For every 10% increase, mean ECV portended to a 2.8-fold adjusted increase risk to MACE (p < 0.001).ConclusionsIn this study of patients with NIDCM, mapping the myocardial extent of abnormality using ECV offers prognostication toward heart failure outcomes incremental to LGE or native T1 mapping.     

Right Ventricular Abnormalities on Cardiovascular Magnetic Resonance Imaging in Patients With Sarcoidosis

ObjectivesThis study aimed to determine the prevalence on cardiac magnetic resonance (CMR) of right ventricular (RV) systolic dysfunction and RV late gadolinium enhancement (LGE), their determinants, and their influences on long-term adverse outcomes in patients with sarcoidosis.BackgroundIn patients with sarcoidosis, RV abnormalities have been described on many imaging modalities. On CMR, RV abnormalities include RV systolic dysfunction quantified as an abnormal right ventricular ejection fraction (RVEF), and RV LGE.MethodsConsecutive patients with biopsy-proven sarcoidosis who underwent CMR for suspected cardiac involvement were studied. They were followed for 2 endpoints: all-cause death, and a composite arrhythmic endpoint of sudden cardiac death or significant ventricular arrhythmia.ResultsAmong 290 patients, RV systolic dysfunction (RVEF <40% in men and <45% in women) and RV LGE were present in 35 (12.1%) and 16 (5.5%), respectively. The median follow-up time was 3.2 years (interquartile range [IQR]: 1.6 to 5.7 years) for all-cause death and 3.0 years (IQR: 1.4 to 5.5 years) for the arrhythmic endpoint. On Cox proportional hazards regression multivariable analyses, only RVEF was independently associated with all-cause death (hazard ratio [HR]: 1.05 for every 1% decrease; 95% confidence interval [CI]: 1.01 to 1.09; p = 0.022) after adjustment for left ventricular EF, left ventricular LGE extent, and the presence of RV LGE. RVEF was not associated with the arrhythmic endpoint (HR: 1.01; 95% CI: 0.96 to 1.06; p = 0.67). Conversely, RV LGE was not associated with all-cause death (HR: 2.78; 95% CI: 0.36 to 21.66; p = 0.33), while it was independently associated with the arrhythmic endpoint (HR: 5.43; 95% CI: 1.25 to 23.47; p = 0.024).ConclusionsIn this study of patients with sarcoidosis, RV systolic dysfunction and RV LGE had distinct prognostic associations; RV systolic dysfunction but not RV LGE was independently associated with all-cause death, whereas RV LGE but not RV systolic dysfunction was independently associated with sudden cardiac death or significant ventricular arrhythmia. These findings may indicate distinct implications for the management of RV abnormalities in sarcoidosis.     

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

BackgroundMyocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.ObjectivesThis study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.MethodsIn this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.ResultsOf 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.ConclusionsThe use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.     

Native T1 Mapping in the Diagnosis of Cardiac Allograft Rejection: A Prospective Histologically Validated Study

ObjectivesThis study aimed to determine the role of T₁ mapping in identifying cardiac allograft rejection.BackgroundEndomyocardial biopsy (EMBx), the current gold standard to diagnose cardiac allograft rejection, is associated with potentially serious complications. Cardiac magnetic resonance (CMR)–based T₁ mapping detects interstitial edema and fibrosis, which are important markers of acute and chronic rejection. Therefore, T₁ mapping can potentially diagnose cardiac allograft rejection noninvasively.MethodsPatients underwent CMR within 24 h of EMBx. T₁ maps were acquired at 1.5-T. EMBx-determined rejection was graded according to International Society of Heart and Lung Transplant (ISHLT) criteria.ResultsOf 112 biopsies with simultaneous CMR, 60 were classified as group 0 (ISHLT grade 0), 35 as group 1 (ISHLT grade 1R), and 17 as group 2 (2R, 3R, clinically diagnosed rejection, antibody-mediated rejection). Native T₁ values in patients with grade 0 biopsies and left ventricular ejection fraction >60% (983 ± 42 ms; 95% confidence interval: 972 to 994 ms) were comparable to values in nontransplant healthy control subjects (974 ± 45 ms; 95% confidence interval: 962 to 987 ms). T₁ values were significantly higher in group 2 (1,066 ± 78 ms) versus group 0 (984 ± 42 ms; p = 0.0001) and versus group 1 (1,001 ± 54 ms; p = 0.001). After excluding patients with an estimated glomerular filtration rate <50 ml/min/m², there was a moderate correlation of log-transformed native T₁ with high-sensitivity troponin T (r = 0.54, p < 0.0001) and pro–B-type natriuretic peptide (r = 0.67, p < 0.0001). Using a T₁ cutoff value of 1,029 ms, the sensitivity, specificity, and negative predictive value were 93%, 79%, and 99%, respectively.ConclusionsMyocardial tissue characterization with T₁ mapping displays excellent negative predictive capacity for the noninvasive detection of cardiac allograft rejection and holds promise to reduce substantially the EMBx requirement in cardiac transplant rejection surveillance.     

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

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

Native T1 Mapping,Extracellular Volume Mapping,and Late Gadolinium Enhancement in Cardiac Amyloidosis: A Meta-Analysis

ObjectivesThis study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging for evaluating cardiac amyloidosis (CA).BackgroundCA is a progressive infiltrative process in the extracellular space that is often underdiagnosed and holds a poor prognosis. Cardiac magnetic resonance (CMR) offers novel techniques for detecting and quantifying the disease burden of CA.MethodsWe searched PubMed for published studies using native T1, ECV, or LGE to diagnose and prognosticate CA. A total of 18 diagnostic (n = 2,015) and 13 prognostic studies (n = 1,483) were included for analysis. Pooled sensitivities, specificities, diagnostic odds ratios (DORs) of all diagnostic tests were assessed by bivariate analysis. Pooled hazard ratios (HRs) for mortality for the 3 techniques were determined.ResultsBivariate comparison showed that ECV (DOR: 84.6; 95% confidence interval [CI]: 30.3 to 236.2) had a significantly higher DOR for CA than LGE (DOR: 20.1; 95% CI: 9.1 to 44.1; p = 0.03 vs. ECV). There was no significant difference between LGE and native T1 for sensitivity, specificity, and DOR. HR was significantly higher for ECV (HR: 4.27; 95% CI: 2.87 to 6.37) compared with LGE (HR: 2.60; 95% CI: 1.90 to 3.56; p = 0.03 vs. ECV) and native T1 (HR: 2.04; 95% CI: 1.24 to 3.37; p = 0.01 vs. ECV).ConclusionsECV demonstrates a higher diagnostic OR for assessing cardiac amyloid than LGE and a higher HR for adverse events compared with LGE and native T1. In addition, native T1 showed similar sensitivity and specificity as ECV and LGE without requiring contrast material. Although limited by study heterogeneity, this meta-analysis suggests that ECV provides high diagnostic and prognostic utility for the assessment of cardiac amyloidosis.     

Feasibility and Prognostic Value of Vasodilator Stress Perfusion CMR in Patients With Atrial Fibrillation

ObjectivesThe aim of this study was to assess the feasibility and prognostic value of vasodilator stress perfusion cardiovascular magnetic resonance (CMR) in patients with atrial fibrillation (AF).BackgroundBecause most studies have excluded arrhythmic patients, the prognostic value of stress perfusion CMR in patients with AF is unknown.MethodsBetween 2008 and 2018, consecutive patients with suspected or stable chronic coronary artery disease and AF referred for vasodilator stress perfusion CMR were included and followed for the occurrence of major adverse cardiovascular event(s) (MACE), defined as cardiovascular death or nonfatal myocardial infarction. The diagnosis of AF was defined by 12-lead electrocardiography before and after CMR. Univariate and multivariate Cox regressions were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.ResultsOf 639 patients (mean age 72 ± 9 years, 77% men), 602 (94%) completed the CMR protocol, and 538 (89%) completed follow-up (median 5.1 years); 80 had MACE. Using Kaplan-Meier analysis, the presence of ischemia (hazard ratio [HR]: 7.56; 95% confidence interval [CI]: 4.86 to 11.80) or LGE (HR: 2.41; 95% CI: 1.55 to 3.74) was associated with the occurrence of MACE (p < 0.001 for both). In a multivariate Cox regression including clinical and CMR indexes, the presence of ischemia (HR: 5.98; 95% CI: 3.68 to 9.73) or LGE (HR: 2.61; 95% CI: 1.89 to 3.60) was an independent predictor of MACE (p < 0.001 for both).ConclusionsIn patients with AF, stress perfusion CMR is feasible and has good discriminative prognostic value to predict the occurrence of MACE.     

Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy

BackgroundRisk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal.ObjectivesThe goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM.MethodsThis was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death.ResultsIn 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p < 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%, >35%) was significantly superior to LVEF with the 35% cutoff (Harrell’s C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p < 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF >35% had significantly higher risk (annual event rate 3%; p = 0.007).ConclusionsIn a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation.     

Prediction of long-term survival in patients with transfusion-dependent hemoglobinopathies: Insights from cardiac imaging and ferritin

AimsThe current study evaluated the association of echocardiography, cardiac magnetic resonance (CMR), and ferritin data with 10-year survival in thalassemia patients.MethodsDemographics, ferritin, echocardiography, and CMR parameters of stable consecutive thalassemia patients were prospectively collected.ResultsIn total, 75 patients (mean age 37 ± 11 years, 45% male) with thalassemia were included and dichotomized based on their survival status after a median follow-up period of 10.3 [9.6-10.9] years. Older age (HR: 1.071, p = 0.001), ferritin ≥2000 ng/ml (HR: 4.682, p = 0.007) and ≥1700 ng/ml (HR: 7.817, p = 0.002), elevated LV end-diastolic pressure (HR: 1.019, p = 0.044), TR Vmax >2.8 m/s (HR: 6.845, p = 0.005), and CMR T21 ≤20 msec (HR: 3.602, p = 0.043) and ≤34 msec (HR: 5.854, p = 0.026) were associated with increased all-cause mortality (primary endpoint). A baseline model including age was created and became more predictive of worse survival by adding TR Vmax >2.8 m/s instead of elevated LV end-diastolic pressure (C index 0.767 vs. 0.760, respectively), ferritin ≥1700 ng/ml instead of ≥2000 ng/ml (C index 0.890 vs. 0.807, respectively), or CMR T21≤34 msec instead of ≤20 msec (C index 0.845 vs. 0.839, respectively). Parameters associated with the combined endpoint of cardiac mortality/cardiac hospitalization (secondary endpoint) after adjusting for age were ferritin ≥1700 ng/ml (HR 3.770, p = 0.014), ratio E/A wave >2 (HR 3.565, p = 0.04), TR Vmax >2.8 m/s (HR 4.541, p = 0.049), CMR T21 ≤20 ms (HR 9.462, p = 0.001), and CMR T21 ≤34 ms (HR 11.735, p = 0.002). The model including age and T21 ≤34 ms instead of T21 ≤20 ms was more predictive of the secondary endpoint (C-index 0.844 vs 0.838, respectively).ConclusionsIn thalassemia patients, TR Vmax >2.8 m/s, ferritin ≥2000 ng/ml, and CMR T21 ≤20 ms were associated with worse long-term survival. In the current era of advanced chelation therapy, aiming for ferritin ≤1700 ng/ml and CMR T21 ≥34 ms may improve their prognosis.     

Association between serum uric acid levels and cardiovascular risk factors among adults in India

Background and aimThe objective of this study was to explore the association between serum uric acid (SUA) levels and cardiovascular risk factors in the Indian population.Methods and resultsThis was a cross-sectional, population-based study. The study enrolled adults aged 20 years and above residing in rural, sub-urban, and urban. All participants completed a detailed questionnaire, underwent anthropometric measurements, and had blood samples collected. Participants were divided into three tertiles based on their SUA concentrations. A total of 2976 participants were included in this study, with 865 from rural, 1030 from sub-urban, and 1081 from urban populations. The mean values of cardiovascular risk factors were significantly higher in tertile 3 (p < 0.001) as compared to the other tertiles. However, we observed a negative trend between the increase of SUA and SUA/Scr ratio and HbA1c levels (Pearson correlation r = −0.068; p < 0.001 and r = −0.140; p < 0.001, respectively). The healthy and prediabetic groups did not show any significant change in HbA1c with increasing SUA levels, while an inverse trend was observed in diabetics. In the diabetic population, both men and women showed an inverse trend between increasing SUA levels and HbA1c in both known and newly diagnosed diabetes (p < 0.001).ConclusionsThe study found a positive association between SUA levels and cardiovascular risk factors. However, HbA1c was inversely correlated with increasing SUA tertiles in both known and newly diagnosed diabetes, as compared to the general population. Additionally, both men and women with diabetes consistently showed an inverse relationship between increasing SUA/SCr ratio and HbA1c levels.     

Effect of intermittent and continuous caloric restriction on Sirtuin1 concentration depends on sex and body mass index

Background & aimsThe favorable effect of caloric restriction (CR) on health span is well known and partly mediated by the sirtuin system. Sirtuin1, a regulator of energy homeostasis in response to nutrient availability, is activated by CR. We therefore investigated effects of two different CR regimens on Sirtuin1 concentrations.Methods & resultsThe study included 112 abdominally obese subjects, randomized to intermittent or continuous CR for 1 year. Blood samples and anthropometric measures were collected at baseline and after 12 months. Sirtuin1 concentrations were measured by ELISA. Sirtuin1 correlated significantly to BMI at baseline (r = .232, p = 0.019). Mean reduction in body-weight was 8.0 and 9.0 kg after intermittent and continuous CR, respectively. After 1 year, no significant between-group differences in Sirtuin1 levels were observed according to regimen (p = 0.98) and sex (p = 0.41). An increase in median Sirtuin1 concentrations (pg/mL) [25, 75 percentiles] from baseline was observed after intermittent CR in the total population (884 [624, 1285] vs.762 [530, 1135]; p = 0.041), most marked in men (820 [623, 1250] vs. 633 [524, 926]; p = 0.016). Improvement in BMI after 1 year correlated to Sirtuin1 changes, but varied according to sex. In women, Spearman's rho = .298, p = 0.034, with stronger correlation in the intermittent CR group (r = .424, p = 0.049). In men, there was an inverse relation to Sirtuin1 changes, only in the intermittent CR group (r = ?.396, p = 0.045).ConclusionsEffects on Sirtuin1 concentrations after 1 year of CR are sex and BMI-related. Intermittent CR regimen affected Sirtuin1 to a stronger extent than continuous CR, suggesting individualized dietary intervention.     

Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques

ObjectivesThis study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA).BackgroundCoronary ¹⁸F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and ¹⁸F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized.MethodsPatients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm³). Patients with HRPs were recruited to undergo ¹⁸F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected ¹⁸F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured.ResultsForty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary ¹⁸F-NaF activity. Lesions with ¹⁸F-NaF uptake had higher surrounding PCAT density than those without ¹⁸F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). ¹⁸F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with ¹⁸F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP).ConclusionsIn patients with HRP features on coronary CTA, increased density of PCAT was associated with focal ¹⁸F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by ¹⁸F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.