OBJECTIVES: The aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm.
METHODS: One hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction.
RESULTS: Adults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio.
CONCLUSIONS: Preterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments.
Objective: To investigate whether changes observed in LV structure and function in preterm-born adults make them more susceptible to cardiac remodeling in association with blood pressure elevation.
Design, Setting, and Participants: This cross-sectional cohort study, conducted at the Oxford Cardiovascular Clinical Research Facility and Oxford Centre for Clinical Magnetic Resonance Research, included 468 adults aged 18 to 40 years. Of these, 200 were born preterm (<37 weeks' gestation) and 268 were born at term (≥37 weeks' gestation). Cardiac magnetic resonance imaging was used to characterize LV structure and function, with clinical blood pressure readings measured to assess hypertension status. Demographic and anthropometric data, as well as birth history and family medical history information, were collected. Data were analyzed between January 2012 and February 2021.
Main Outcomes and Measures: Cardiac magnetic resonance measures of LV structure and function in response to systolic blood pressure elevation.
Results: The cohort was primarily White (>95%) with a balanced sex distribution (51.5% women and 48.5% men). Preterm-born adults with and without hypertension had higher LV mass index, reduced LV function, and smaller LV volumes compared with term-born individuals both with and without hypertension. In regression analyses of systolic blood pressure with LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm-born compared with term-born adults. Compared with term-born adults, there was a 2.5-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in very and extremely preterm-born adults (<32 weeks' gestation) (0.394 g/m2 vs 0.157 g/m2 per 1 mm Hg; P
OBJECTIVES: Using diffusion tensor cardiac magnetic resonance (DT-CMR) we assessed myocardial disarray and fibrosis in both SARC+LVH- and HCM patients and evaluated the relationship between microstructural alterations and electrocardiographic (ECG) parameters associated with arrhythmic risk.
METHODS: Sixty-two individuals (24 SARC+LVH-, 24 HCM and 14 matched controls) were evaluated with multiparametric CMR including stimulated echo acquisition mode (STEAM) DT-CMR, and blinded quantitative 12-lead ECG analysis.
RESULTS: Mean diastolic fractional anisotropy (FA) was reduced in HCM compared to SARC+LVH- and controls (0.49±0.05 vs 0.52±0.04 vs 0.53±0.04, p=0.009), even after adjustment for differences in extracellular volume (ECV) (p=0.038). Both HCM and SARC+LVH- had segments with significantly reduced FA relative to controls (54% vs 25% vs 0%, p=0.002). Multiple repolarization parameters were prolonged in HCM and SARC+LVH-, with corrected JT interval (JTc) being most significant (354±42ms vs 356±26ms vs 314±26ms, p=0.002). Among SARC+LVH-, JTc duration correlated negatively with mean FA (r=-0.6, p=0.002). In HCM, the JTc interval showed a stronger association with ECV (r=0.6 p=0.019) than FA (r=-0.1 p=0.72). JTc discriminated SARC+LVH- from controls (Area-under-the-receiver-operator-curve 0.88, CI 0.76-1.00, p<0.001), and in HCM correlated with the ESC HCM sudden cardiac death risk score (r=0.5, p=0.014).
CONCLUSION: Low diastolic FA, suggestive of myocardial disarray, is present in both SARC+LVH- and HCM. Low FA and raised ECV were associated with repolarization prolongation. Myocardial disarray assessment using DT-CMR and repolarization parameters such as the JTc interval demonstrate significant potential as markers of disease activity in HCM.
METHODS: Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.
RESULTS: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max.
CONCLUSIONS: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
OBJECTIVES: This study sought to evaluate the safety and efficacy of ninerafaxstat in nHCM.
METHODS: Patients with hypertrophic cardiomyopathy and left ventricular outflow tract gradient <30 mm Hg, ejection fraction ≥50%, and peak oxygen consumption <80% predicted were randomized to ninerafaxstat 200 mg twice daily or placebo (1:1) for 12 weeks. The primary endpoint was safety and tolerability, with efficacy outcomes also assessed as secondary endpoints.
RESULTS: A total of 67 patients with nHCM were enrolled at 12 centers (57 ± 11.8 years of age; 55% women). Serious adverse events occurred in 11.8% (n = 4 of 34) in the ninerafaxstat group and 6.1% (n = 2 of 33) of patients in the placebo group. From baseline to 12 weeks, ninerafaxstat was associated with significantly better VE/Vco2 (ventilatory efficiency) slope compared with placebo with a least-squares (LS) mean difference between the groups of -2.1 (95% CI: -3.6 to -0.6; P = 0.006), with no significant difference in peak VO2 (P = 0.90). The Kansas City Cardiomyopathy Questionnaire Clinical Summary Score was directionally, though not significantly, improved with ninerafaxstat vs placebo (LS mean 3.2; 95% CI: -2.9 to 9.2; P = 0.30); however, it was statistically significant when analyzed post hoc in the 35 patients with baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score ≤80 (LS mean 9.4; 95% CI: 0.3-18.5; P = 0.04).
CONCLUSIONS: In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a phase 3 study.
DESIGN: Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations.
RESULTS: Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (<1.3; ≥2.67) followed by LSM-VCTE cut-offs (<8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (<1.3; ≥3.48) followed by LSM cut-offs (<8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy.
CONCLUSION: Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies.