Impact of Ventricular Morphology on Fiber Stress and Strain in Fontan Patients.

BACKGROUND: Right ventricular (RV) morphology has been associated with adverse clinical outcomes in Fontan patients. The impact of RV versus left ventricular morphology on ventricular stress and strain in single ventricles is not well known. METHODS AND RESULTS: Cardiac magnetic resonance examinations in 193 patients with the Fontan circulation were retrospectively analyzed. Ventricular mass, volume, global circumferential and longitudinal strain, and global average end-systolic fiber stress were calculated using previously published methods. Compared with left ventricular morphology, RV morphology (48%) was associated with higher ventricular end-diastolic volume (110 mL/BSA1.3 versus 84 mL/BSA1.3, P<0.001), lower mass-to-volume ratio (0.46 versus 0.57, P<0.001), higher global average end-systolic fiber stress (23 kPa versus 20 kPa, P=0.002), worse global circumferential strain (-21% versus -24%, P<0.001), and higher prevalence of greater than or equal to moderate atrioventricular valve regurgitation (25% versus 6%, P<0.001). Ejection fraction and global longitudinal strain were similar between the groups. Death or listing for heart transplantation occurred in 24 (12%) with a median follow-up of 6.2 years. On univariate analysis, RV morphology, ventricular dilatation, and worse global circumferential strain were associated with this composite outcome. CONCLUSIONS: In comparison to Fontan patients with a dominant left ventricle, those with a dominant RV have higher fiber stress, a higher rate of ventricular dilatation, lower circumferential fiber shortening, and similar longitudinal shortening. RV morphology, ventricular dilation, and worse circumferential strain are associated with death or heart transplantation. The difference in myofiber architecture may contribute to suboptimal adaptation of the RV as a systemic ventricle.

Inefficient Ventriculoarterial Coupling in Fontan Patients: A Cardiac Magnetic Resonance Study.

The ventriculoarterial coupling (VAC) ratio, the ratio of arterial elastance (Ea) to ventricular end-systolic elastance (Ees), reflects cardiovascular efficiency. Little is known about this ratio in patients who have undergone the Fontan procedure. Our aim was to assess the VAC ratio in a cohort of Fontan patients using a cardiac magnetic resonance (CMR) method, and to examine its relation to outcomes. We retrospectively assessed VAC from CMR data on 195 Fontan patients (age 19.6 ± 10.7 years) and 42 controls (age 15.2 ± 2.2 years). The VAC ratio was calculated as Ea/Ees (Ea = mean arterial blood pressure (MBP)/ventricular stroke volume; Ees = MBP/end-systolic volume). Compared with controls, Fontan patients had lower body surface area-adjusted median Ees (1.54 vs. 2.4, p < 0.001) and Ea (1.35 vs. 1.48, p = 0.01), and a higher median VAC ratio (0.88 vs. 0.62, p < 0.001). After a median follow-up of 4 years (range 1-10), 20 patients reached a composite endpoint of death or heart transplant listing. On multivariable modeling, being in the lowest tertile of the VAC ratio was independently associated with the composite endpoint (odds ratio 11.39, p = 0.02), and inclusion of the VAC ratio in the model improved prediction compared to traditional risk factors. In patients without ventricular dilation, the VAC ratio was the only factor predictive of the composite endpoint (p = 0.02). In conclusion, we found evidence for inefficient ventriculoarterial coupling in Fontan patients. The VAC ratio improved prediction of outcomes and was especially useful in patients without ventricular dilation. Further investigation into the clinical significance of ventriculoarterial coupling in this patient population is warranted.

Enhanced thermal imaging of wound tissue for better clinical decision making.

Infrared cameras are increasingly applied in clinical applications as they allow fast, inexpensive and non-contact temperature measurements. As abnormal heat distribution can indicate illness, infrared cameras have been applied in the prediction, diagnosis and monitoring of medical conditions. Current practices, however, often overlook the importance of emissivity when taking thermal measurements. The consensus is that human skin has an emissivity of 0.98 but this value varies between individuals, areas examined, and if the skin is damaged. In particular, further research should be conducted on the emissivity variations of wounds. OBJECTIVE: This research investigated the emissivity variation of chronic wounds and its effect on thermal measurements. Eleven patients with non-infected foot ulcers were recruited. Three non-diabetic wounds were also investigated in a clinical setting. APPROACH: A reflectance based method was used which involved alternating shades at different temperatures over the region of interest. Based on the change in the thermal images, emissivity was calculated at each pixel. MAIN RESULTS: Overall, it was found that the emissivity of wounds was similar or slightly higher to intact skin (range 0.01-0.03 higher with an average value of 0.97 ± 0.03), with lower values at wound edges (on average 0.02 lower than intact skin). Correcting for emissivity resulted in an average temperature difference of 0.83% in the thermal images. SIGNIFICANCE: Despite the similarity in emissivity, the difference between the original thermal image and the emissivity corrected thermal image in some cases was substantial. These differences could prove significant in clinical evaluations, indicating the need to incorporate emissivity measurement into standard protocol to ensure utmost accuracy.

Factors associated with severe aortic dilation in patients with Fontan palliation.

OBJECTIVE: To describe the range of aortic dimensions and severity of aortic valve regurgitation (AR) in patients after the Fontan operation, examine rate of growth over time and identify risk factors for severe aortic dilation. METHODS: This was a single-centre retrospective study of Fontan patients who underwent magnetic resonance angiography. RESULTS: Between 2005 and 2014, there were 235 patients (median age 18.8 years). The aortic root (median Z-score 3.2) and ascending aorta (AAo) (median Z-score 4.1) were dilated. Severe aortic root or AAo dilation (Z-score ≥6.0) was present in 8.5% and 22%, respectively. Multivariable analysis identified older age at Fontan (adjusted odds ratio (AOR): 1.1 per year; 95% CI 1.04 to 1.2; p=0.002), male gender (AOR: 16.3; 95% CI 1.8 to 144.9; p=0.01) and higher mean blood pressure (AOR: 1.5 per 10 mm Hg; 95% CI 1.01 to 2.3; p=0.05) as factors associated with severe aortic root dilation. Older age at Fontan (AOR: 1.1 per year; 95% CI 1.02 to 1.1; p=0.01), male gender (AOR: 3.3; 95% CI 1.5 to 7.5; p=0.004) and left ventricular morphology (AOR: 2.6; 95% CI 1.3 to 5.1; p=0.007) were associated with severe AAo dilation. Over a median of 3.3 years, there was no significant increase in aortic dimension. Most patients (96%) had mild or less AR. CONCLUSIONS: The Fontan aorta is enlarged at the aortic root and AAo. Older age at Fontan, male gender, elevated blood pressure and left ventricular morphology are associated with severe aortic dilation. Although trivial-mild AR is common, significant regurgitation is infrequent.

TMEM14C is required for erythroid mitochondrial heme metabolism.

The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.