A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features.

BACKGROUND: Primary carnitine deficiency (PCD) denotes low carnitine levels with an autosomal recessive pattern of inheritance. Cardiomyopathy is the most common cardiac symptom in patients with PCD, and early diagnosis can prevent complications. Next-generation sequencing can identify genetic variants attributable to PCD efficiently. OBJECTIVE: We aimed to detect the genetic cause of the early manifestations of hypertrophic cardiomyopathy and metabolic abnormalities in an Iranian family. METHODS: We herein describe an 8-year-old boy with symptoms of weakness and lethargy diagnosed with PCD through clinical evaluations, lab tests, echocardiography, and cardiac magnetic resonance imaging. The candidate variant was confirmed through whole-exome sequencing, polymerase chain reaction, and direct Sanger sequencing. The binding efficacy of normal and mutant protein-ligand complexes were evaluated via structural modeling and docking studies. RESULTS: Clinical evaluations, echocardiography, and cardiac magnetic resonance imaging findings revealed hypertrophic cardiomyopathy as a clinical presentation of PCD. Whole-exome sequencing identified a new homozygous variant, SLC22A5 (NM_003060.4), c.821G > A: p.Trp274Ter, associated with carnitine transport. Docking analysis highlighted the impact of the variant on carnitine transport, further indicating its potential role in PCD development. CONCLUSIONS: The c.821G > A: p.Trp274Ter variant in SLC22A5 potentially acted as a pathogenic factor by reducing the binding affinity of organic carnitine transporter type 2 proteins for carnitine. So, the c.821G > A variant may be associated with carnitine deficiency, metabolic abnormalities, and cardiomyopathic characteristics.

Myocardial and Vascular Involvement in Patients with Takayasu Arteritis: A Cardiovascular MRI Study.

We aimed to explore the cardiovascular magnetic resonance (CMR) of Takayasu arteritis (TA) and its cardiovascular complications. CMR was conducted on 37 TA patients and 28 healthy individuals. We evaluated the CMR findings and adverse cardiovascular complications at the time of the CMR (ACCCMR). After 8 to 26 months, the major adverse cardiac and cerebrovascular events (MACCEs) were evaluated. The TA included 25 women (67.6%), aged 36 ± 16 years old, and 28 age- and sex-matched healthy controls. Left ventricular (LV) ejection fraction was significantly lower in the TA group than in the control group (51 ± 9% vs. 58 ± 1.7%; p < 0.001). Aortic mural edema was present in 34 patients (92%) and aortic mural hyperenhancement in 36 (97%). Left ventricular global longitudinal strain (LVGLS) was significantly lower in the TA group (median [interquartile range] = 13.70 [3.27] vs. 18.08 [1.35]; p < 0.001). ACCCMR was seen in 13 TA patients (35.1%), with the most common cardiac complication being myocarditis (16.2%). During a median follow-up of 18 months (8-26 months), nine patients developed MACCEs, of which the most common was cerebrovascular accident in five (13.5%). The LVGLS of the CMR had the strongest association with complications. Myocardial strain values, especially LVGLS, can reveal concurrent and future cardiovascular complications in TA patients.

Computed Tomography-Based Coronary Artery Calcium Score Calculation at a Reduced Tube Voltage Utilizing Iterative Reconstruction and Threshold Modification Techniques: A Feasibility Study.

BACKGROUND: The coronary artery calcium score (CACS) indicates cardiovascular health. A concern in this regard is the ionizing radiation from computed tomography (CT). Recent studies have tried to introduce low-dose CT techniques to assess CACS. We aimed to investigate the accuracy of iterative reconstruction (IR) and threshold modification while applying low tube voltage in coronary artery calcium imaging. METHODS: The study population consisted of 107 patients. Each subject underwent an electrocardiogram-gated CT twice, once with a standard voltage of 120 kVp and then a reduced voltage of 80 kVp. The standard filtered back projection (FBP) reconstruction was applied in both voltages. Considering Hounsfield unit (HU) thresholds other than 130 (150, 170, and 190), CACS was calculated using the FBP-reconstructed 80 kVp images. Moreover, the 80 kVp images were reconstructed utilizing IR at different strength levels. CACS was measured in each set of images. The intraclass correlation coefficient (ICC) was used to compare the CACSs. RESULTS: A 64% reduction in the effective dose was observed in the 80 kVp protocol compared to the 120 kVp protocol. Excellent agreement existed between CACS at high-level (strength level = 5) IR in low-kVp images and the standard CACS protocol in scores ≥ 11 (ICC > 0.9 and p < 0.05). Increasing the threshold density to 190 HU in FBP-reconstructed low-kVp images yielded excellent agreement with the standard protocol in scores ≥ 11 (ICC > 0.9 and p < 0.05) and good agreement in score zero (ICC = 0.84 and p = 0.02). CONCLUSIONS: The modification of the density threshold and IR provides an accurate calculation of CACS in low-voltage CT with the potential to decrease patient radiation exposure.

The predictive value of cardiac MRI strain parameters in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction and a low fibrosis burden: a retrospective cohort study.

Background: Prompt interventions prevent adverse events (AE) in hypertrophic cardiomyopathy (HCM). We evaluated the pattern and the predictive role of feature tracking (FT)-cardiac magnetic resonance (CMR) imaging parameters in an HCM population with a normal left ventricular ejection fraction (LVEF) and a low fibrosis burden. Methods: The CMR and clinical data of 170 patients, consisting of 142 HCM (45 ± 15.7 years, 62.7% male) and 28 healthy (42.2 ± 11.26 years, 50% male) subjects, who were enrolled from 2015 to 2020, were evaluated. HCM patients had a normal LVEF with a late gadolinium enhancement (LGE) percentage below 15%. Between-group differences were described, and the potent predictors of AE were determined. A P-value below 0.05 was considered significant. Results: LV global longitudinal, circumferential, and radial strains (GLS, GCS, and GRS, respectively) and the LV myocardial mass index (MMI) were different between the healthy and HCM cases (all Ps < 0.05). Strains were significantly impaired in the HCM patients with a normal MMI. A progressive decrease in LVGLS and a distinct fall in LVGCS were noted with a rise in MMI. AE were predicted by LVGLS, LVGCS, and the LGE percentage, and LVGCS was the single robust predictor (HR, 1.144; 95% CI, 1.080-1.212; P = 0.001). An LVGCS below 16.2% predicted AE with 77% specificity and 58% sensitivity. Conclusions: LV strains were impaired in HCM patients with a normal EF and a low fibrosis burden, even in the presence of a normal MMI. CMR parameters, especially FT-CMR values, predicted AE in our HCM patients.