Peak Apical Recoil Rate is a Simplified Index of Left Ventricular Untwist: Validation and Application for Assessment of Diastolic Function in Children

AimsTo simplify measurement of untwist by measuring the recoil rate of LV apex only, to validate and apply peak apical recoil rate (PARR) as an index of diastolic dysfunction (DD) in pediatric subjects during increased and decreased lusitropic states. Methods and ResultsWe recruited 153 healthy subjects (mean age 13.8+2.9 years), of whom 48 performed straight leg raising exercise and an additional 46 patients (mean 8.4+5.6 years) with documented pulmonary capillary wedge pressures (PCWP) (validation cohort). In addition, we studied 16 dilated cardiomyopathy patients (mean age 9.5+6.3years) (application cohort). PARR and isovolumic relaxation time (IVRT) were compared to PCWP. Both PARR and PARR normalized by heart rate (nPARR) were excellent in detecting patient with PCWP >12 mmHg and greatly superior to IVRT in this respect (AUC: 0.98, 95% CI [0.96, 1.0] vs. AUC: 0.7 95%CI [0.54,0.86]). In DCM patients, PARR and nPARR were greatly decreased compared to controls (-38.58+18.59º/s vs -63.07+16.35º /s, p< 0.001) and (-0.43+0.20 º/ s/min vs -0.83+0.28º/s/min, p<0.0001) but increased with straight leg raising exercise (-59.4+19.4º/s vs -97.82+39.0 º/s, p<0.01) and -0.85+0.36 vs -1.4+0.62 º/s/min (p< 0.0001). The intra-observer and inter-observer intraclass correlation (ICC) coefficients were 0.95 and 0.88, respectively.ConclusionPARR successfully detected increased and decreased lusitropic states and was not affected by age when normalized with heart rate. Both PARR and nPARR are superior to IVRT in their correlation with PCWP and offer incremental value over traditional indices of DD. This highly reproducible parameter may potentially serve as a useful index of elevated PCWP in children.

Transesophageal Versus Transthoracic Echocardiography for Assessment of Left Ventricular Diastolic Function

Background: Transesophageal echocardiography (TEE) has not been compared to transthoracic echocardiography (TTE) for assessment of left ventricular diastolic function (LVDF). Left ventricular diastolic dysfunction is common in systemic lupus erythematosus (SLE), a disease model of premature myocardial disease. Methods: 66 patients with SLE (mean age 36±12 years, 91% women) and 26 age-and-sex matched healthy volunteers (mean age 34±11 years, 85% women) underwent TEE immediately followed by TTE. From basal four-chamber views, mitral inflow E and A velocities, E/A ratio, E deceleration time, isovolumic relaxation time, septal and lateral mitral E’ and A’ velocities, septal E’/A’ ratio, mitral E to septal and lateral E’ ratios, and pulmonary veins systolic to diastolic peak velocities ratio were measured. Measurements were averaged over 3 cardiac cycles and performed by 2 independent observers. Results: LVDF parameters were worse in patients than in controls by TEE and TTE (all p≤0.03). Most LVDF parameters were similar within each group by TEE and TTE (all p≥0.17). By both techniques, mitral E and A, mitral and septal E/A ratios, septal and lateral E’, septal and lateral E/E’ ratios, and average E/E’ ratio were highly correlated (r=0.64-0.96, all p≤0.003); E deceleration time, isovolumic relaxation time, and septal A’ velocities were moderately correlated (r=0.43-0.54, all p≤0.03); and pulmonary veins systolic to diastolic ratio showed the lowest correlation (r=0.27, p=0.04). Conclusion: By TEE and TTE, LVDF parameters were worse in SLE patients than in controls; and in both groups, LVDF parameters assessed by TEE and TTE were similar and significantly correlated.

The Impact of Delivery Type on Ventricular Performances of Healthy Neonates

<p><strong>Objective:</strong> The present study aims to evaluate how the mode of delivery affects the alterations in myocar­dial functions of healthy newborns within the first month of life. </p><p><strong>study desıgn:</strong> This is a prospective review of 60 healthy term newborns whose cardiac functions were examined by M-mode and tissue Doppler echocardiography on the first day of their lives and subsequently at one month of age. </p><p><strong>Results:</strong> At the first visit, the tricuspid annular plane systolic excursion was significantly higher in vaginally delivered newborns. Mitral and tricuspid E velocities and E/E’ ratio of the right ventricle and isovolumic relaxation time of right ventricle were also significantly higher in newborns delivered by cesarean section. Both of the groups had statistically similar M-mode and tissue Doppler echocardiography measurements at the time of the second visit. Only the increase in the tricuspid A velocity and myocardial performance index measured from septum between the first and second visits were significantly higher in the cesarean delivery group. When compared with the first visit, both isovolumic contraction time and isovolumic relaxation time were lower between the groups but myocardial performance index values were increased without significance at the second visit.</p><p><strong>Conclusion:</strong> Diastolic indices were significantly elevated in newborns delivered by cesarean section than neonates delivered by vaginal route. After one-month-long follow up, an increase was observed in diastolic ventricle functions of the vaginally delivered newborns but this increase was statistically insignificant. Cesarean delivery might be associated with the impairment in ventricular functions and, thus, a delay in the improvement and maturation of cardiac functions.</p>

Impaired systolic and diastolic left ventricular function in children and adolescents with congenital adrenal hyperplasia receiving corticosteroid therapy

AimThe present study aimed to evaluate systolic and diastolic myocardial function in children and adolescents with congenital adrenal hyperplasia.MethodsThe study included 44 children with the diagnosis of classic congenital adrenal hyperplasia and 39 healthy children whose age, pubertal status, and gender were similar to those of the patient group. Anthropometric parameters and 17-hydroxyprogesterone levels were measured, and bone age was calculated. The average daily hydrocortisone dose was calculated over the last 1-year file records. Hyperandrogenic state was defined according to bone age SD score (⩾2) and 17-hydroxyprogesterone levels (>10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging.ResultsPatients had higher morphological parameters, such as left ventricular end-systolic diameter, interventricular septal thickness at end diastole, left ventricular posterior wall thickness at end diastole, left ventricular mass and index, than the control group (p<0.05). On pulsed-wave and tissue Doppler echocardiography, significant subclinical alterations were observed in systolic (isovolumic contraction time), diastolic (isovolumic relaxation time), and global left ventricular functional (myocardial performance index) parameters in the congenital adrenal hyperplasia group compared to the control group (p<0.05). In partial correlation analyses, after controlling the effect of hyperandrogenism, the mean hydrocortisone dosage was positively correlated with isovolumic relaxation time in congenital adrenal hyperplasia group (p<0.05).ConclusionThis study demonstrated that the patients with congenital adrenal hyperplasia are at risk for left ventricular hypertrophy, systolic and diastolic myocardial subclinical alterations. Overtreatment may be responsible for the increased risk of myocardial dysfunction in patients with congenital adrenal hyperplasia.

Childhood and adult exposure to secondhand tobacco smoke and cardiac structure and function: results from Echo-SOL

ObjectiveTo describe the relationship of household secondhand smoke (SHS) exposure and cardiac structure and function.MethodsParticipants (n=1069; 68 % female; age 45–74 years) without history of tobacco use, coronary artery disease or severe valvular disease were included. Past childhood (starting at age <13 years), adolescent/adult and current exposure to household SHS was assessed. Survey linear regression analyses were used to model the relationship of SHS exposure and echocardiographic measures of cardiac structure and function, adjusting for covariates (age, sex, study site, alcohol use, physical activity and education).ResultsSHS exposure in childhood only was associated with reduced E/A velocity ratio (β=−0.06 (SE 0.02), p=0.008). SHS exposure in adolescence/adult only was associated with increased left ventricular ejection fraction (LVEF) (1.2 (0.6), p=0.04), left atrial volume index (1.7 (0.8), p=0.04) and decreased isovolumic relaxation time (−0.003 (0.002), p=0.03). SHS exposure in childhood and adolescence/adult was associated with worse left ventricular global longitudinal strain (LVGLS) (two-chamber) (0.8 (0.4), p= 0.049). Compared with individuals who do not live with a tobacco smoker, individuals who currently live with at least one tobacco smoker had reduced LVEF (−1.4 (0.6), p=0.02), LVGLS (average) (0.9 (0.40), p=0.03), medial E′ velocity (−0.5 (0.2), p=0.01), E/A ratio (−0.09 (0.03), p=0.003) and right ventricular fractional area change (−0.02 (0.01), p=0.01) with increased isovolumic relaxation time (0.006 (0.003), p=0.04).ConclusionsPast and current household exposure to SHS was associated with abnormalities in cardiac systolic and diastolic function. Reducing household SHS exposure may be an opportunity for cardiac dysfunction prevention to reduce the risk of future clinical heart failure.

Reactive Oxygen Species Produced by NADPH Oxidase Contribute to Cardiac Pathology in a Mouse Model of Sickle Cell Disease

Cardiopulmonary complications are an important contributor to morbidity and mortality in patients with sickle cell anemia (SCA). We have recently discovered that patients with SCA develop cardiomyopathy with restrictive pattern, characterized by diastolic dysfunction with progressive left atrial dilation, superimposed on the anemia-associated hyperdynamic physiology causing hypertrophied, dilated ventricles (Niss et al, JACC: Cardiovascular Imaging, 2016). Using a longitudinal systematic analysis of mouse models of SCA versus mice with iron-deficiency anemia, we found that this unique cardiomyopathy is indeed not due to chronic anemia and is associated with upregulation of genes related to oxidative stress pathways (Bakeer et al, PNAS, in press). These findings along with the known fact of increased inflammation and oxidative stress in SCA led us to postulate that NADPH oxidase (Nox)-mediated reactive oxygen species (ROS) may be an important pathogenic mechanism underlying cardiomyopathy in SCA and consequently mice lacking Nox-mediated ROS might be relatively protected from cardiac dysfunction. To investigate the role of NADPH oxidase in SCA cardiovascular pathophysiology, we bred the knock-in humanized SCA murine model Hbbtm2(HBG1,HBB*)Tow (where mouse α- and β-globin genes have been replaced by the human α- and βS globin genes; commonly known as UAB mice and herein called SS mice) with mice knocked out for the p22phox subunit of NADPH oxidase (a common subunit for all mouse Nox isoforms). We evaluated the phenotype of SS;p22phox-/- mice in blood and determined their cardiac function as compared to SS (p22phox+/+) littermate control mice. Hemolysis and ensuing reticulocytosis did not appear significantly improved in the SS;p22phox-/- mice; red blood cell (RBC) ROS was also stable likely due to the major contribution of mitochondrial ROS in the reticulocytes. Baseline ROS levels in the neutrophils of SS;p22phox-/-mice were similar to the levels in SS mice, but inducible ROS was almost eliminated as expected with deficiency of the p22phox subunit and inactivation of all NADPH oxidase isoforms. Starting at 8 weeks of age, cardiac structure and function were assessed on age-matched SS and SS;p22phox-/- mice by serial echocardiography. We studied 3 timepoints: 8-15 weeks of age, 16-24 weeks, and 25-34 weeks. SS mice developed progressively increased left atrial dimension (LAd) starting at 16 weeks of age while SS;p22phox-/- mice had stable LAd, with values similar to WT (Figure 1A). This difference became more pronounced with aging (P=0.02 at 25-34 weeks). Isovolumic relaxation time (IVRT), the time interval between closure of the aortic valve and opening of the mitral valve, was prolonged in the SS mice older than 16 weeks of age, consistent with diastolic dysfunction. In contrast, SS;p22phox-/- mice had no change in IVRT (Figure 1B). Also consistent with diastolic dysfunction, the ratio of transmitral E and e-(MV IVS E/e-) was increased in the SS group vs SS;p22phox-/-. Finally, the SS mice showed elevated left ventricular (LV) mass and decreased LV shortening fraction by 22-34 weeks whereas these parameters were preserved in the SS;p22phox-/-mice. Histopathology studies were performed to evaluate changes in the cardiac tissue. In the SS mice, H&E, picrosirius red and Masson trichrome staining showed not only significant LV hypertrophy and dilation but also significant interstitial fibrosis. Immunostaining for the extracellular matrix proteins collagen and fibronectin, showed extensive deposition of these proteins in the SS mouse heart. In contrast, SS; p22phox-/-mouse hearts were relatively spared. In conclusion, our data show that SS;p22phox-/-mice demonstrate better preserved diastolic and systolic heart function compared to SS mice, and decreased heart tissue damage. These findings suggest that therapeutic manuevers aimed at decreasing oxidative stress in SCA may be an effective strategy to counter SCA cardiomyopathy. Figure 1 Echocardiographic parameters evaluating diastolic function of the heart of SS vs SS;p22phox-/-mice. A. Left atrial dimension (LAd). B. Isovolumic relaxation time (IVRT). SS: Hbbtm2(HBG1,HBB*)Tow (UAB) with wild-type p22phox; SS;p22phox-/-: UAB mice with targetted deletion of p22phox.(statistical analysis was performed using Wilcoxon rank-sum test; JMP 9.0 SAS Institute, Cary, North Carolina) Figure 1. Echocardiographic parameters evaluating diastolic function of the heart of SS vs SS;p22phox-/-mice. A. Left atrial dimension (LAd). B. Isovolumic relaxation time (IVRT). SS: Hbbtm2(HBG1,HBB*)Tow (UAB) with wild-type p22phox; SS;p22phox-/-: UAB mice with targetted deletion of p22phox.(statistical analysis was performed using Wilcoxon rank-sum test; JMP 9.0 SAS Institute, Cary, North Carolina) Disclosures No relevant conflicts of interest to declare.