Erratum to: Abnormal Myocardial Strain Indices in Children Receiving Anthracycline Chemotherapy.

Erratum to: Pediatr Cardiol DOI 10.1007/s00246-015-1203-8. The original version of this article unfortunately contained a mistake in the author's group. The given name of Payam Ghazi was misspelled and the first and middle names of John Lynn Jefferies were interchanged. The two co-author names are corrected with this erratum.

Abnormal Myocardial Strain Indices in Children Receiving Anthracycline Chemotherapy.

Anthracycline chemotherapy (AC) is associated with impaired left ventricular (LV) systolic function. LV ejection fraction (EF %) obtained by two-dimensional echocardiography is the current gold standard for detection and monitoring of LV systolic function. However, dependence on LVEF has been shown to be unreliable due to its inherent limitations. Speckle tracking echocardiography (STE) measures myocardial strain and is a sensitive method to detect LV systolic dysfunction with demonstrated utility in such detection in adult and pediatric cohort studies. Compare myocardial strain indices derived by STE with LVEF to detect ACT-induced LV systolic dysfunction. Prospective, cross-sectional measurements of LV myocardial strain indices derived from STE with LVEF. Pediatric cohort of 25 patients (pts): 17 females, eight males with a mean age 9.8 ± 5.8 years, who received anthracyclines (AC); median cumulative dose ≥150 ± 124.4 mg/m(2), range 60-450 mg/m(2) showing normal LV end-diastolic diameter (mm) and normal LVEF (≥55 %) underwent STE to obtain LV myocardial strain indices: strain and strain rate. The inter- and intraobserver variability for the strain indices was 5 %. Fifteen of 25 pts (60 %) showed abnormal global longitudinal peak systolic strain (GLPSS) and 19/25 pts (76 %) showed abnormal peak circumferential strain (PCS) compared to age-matched controls (p = 0.005). In contrast, no significant differences was observed in either indices with the dose of AC. Likewise, no significant changes in the systolic or diastolic strain rate were noted with the dose of AC (r (2) = 0.0076 for peak E, r (2) = 0.072 for peak A, p = NS). GLPSS and PCS were diminished and, however, correlated poorly with the cumulative dose of AC. These observations indicate an early onset of LV systolic dysfunction by the strain indices in pts who continue to show a normal LVEF implying presence of occult LV systolic dysfunction. These novel strain indices may assist in early detection of LV systolic dysfunction with implications for monitoring and prevention of AC-induced LV systolic dysfunction.

Functional changes in pulmonary arterial endothelial cells associated with BMPR2 mutations.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by abnormal remodeling of small, peripheral pulmonary arteries. Germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene are a major risk factor for developing PAH. At present, the correlation between the BMPR2 mutation and the patient's prognosis remains controversial despite several investigations. In this study, we explored the functional effects of four BMPR2 mutations to dissect the functional significance of the BMPR2 gene defect. Cellular immunofluorescence assay of four mutants (Tyr67Cys, Thr268fs, Ser863Asn, and Gln433X) revealed that the BMPR2 protein containing Thr268fs, Ser863Asn, or Gln433X exhibited abnormal subcellular localization. The BrdU incorporation and TUNEL assay suggested that any of the BMPR2 mutations Thr268fs, Ser863Asn, or Gln433X could improve endothelial cell apoptosis and decrease cell proliferation. All of the four mutants could inhibit nitric oxide (NO) synthesis in HLMVE cells, and ET-1 levels increased in the cells transfected with mutant Ser863Asn. Our results will improve the understanding of the genotype-phenotype correlations and mechanisms associated with BMPR2 mutations.

Mutations in NEXN, a Z-disc gene, are associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac disorder, is characterized by increased ventricular wall thickness that cannot be explained by underlying conditions, cadiomyocyte hypertrophy and disarray, and increased myocardial fibrosis. In as many as 50% of HCM cases, the genetic cause remains unknown, suggesting that more genes may be involved. Nexilin, encoded by NEXN, is a cardiac Z-disc protein recently identified as a crucial protein that functions to protect cardiac Z-discs from forces generated within the sarcomere. We screened NEXN in 121 unrelated HCM patients who did not carry any mutation in eight genes commonly mutated in myofilament disease. Two missense mutations, c.391C>G (p.Q131E) and c.835C>T (p.R279C), were identified in exons 5 and 8 of NEXN, respectively, in two probands. Each of the two mutations segregated with the HCM phenotype in the family and was absent in 384 control chromosomes. In silico analysis revealed that both of the mutations affect highly conserved amino acid residues, which are predicted to be functionally deleterious. Cellular transfection studies showed that the two mutations resulted in local accumulations of nexilin and that the expressed fragment of actin-binding domain containing p.Q131E completely lost the ability to bind F-actin in C2C12 cells. Coimmunoprecipitation assay indicated that the p.Q131E mutation decreased the binding of full-length NEXN to α-actin and abolished the interaction between the fragment of actin-binding domain and α-actin. Therefore, the mutations in NEXN that we describe here may further expand the knowledge of Z-disc genes in the pathogenesis of HCM.

Enhanced left atrial reservoir, increased conduit, and weakened booster pump function in hypertensive patients with paroxysmal atrial fibrillation.

The aim of this study was to evaluate whether paroxysmal atrial fibrillation (PAF) has an impact on left atrial (LA) function in hypertensive patients and, if so, to select clinical factors influencing this relationship. Sixty-four essential hypertensive patients with PAF (group EHf) and fifty-five patients without PAF (group EH) were enrolled. Using acoustic quantification, the maximal and minimum LA volume (LAVmax, LAVmin), the LA volume at the end of rapid emptying (EREV), and the LA volume at the onset of atrial emptying (OAEV) were measured. The LA total emptying volume (TE; TE=LAVmax-LAVmin), LA rapid emptying volume (RE; RE=LAVmax-EREV), and left atrial ejection fraction (LAEF)=(OAEV-LAVmin)/OAEVx100% were calculated. LAVmax, LAVmax indexed to body surface area (LAVmaxI), TE and RE were significantly increased in group EHf. LAEF was clearly lower in group EHf than in group EH. The linear regression analysis showed that the frequency and total number of PAF episodes were the factors with the greatest influence on LAVmaxI (r=0.787, p<0.05). TE and frequency of PAF episodes were the most influential factors on RE (r=0.902, p<0.01). These results suggest that the occurrence of PAF in hypertensive patients is associated with enhanced LA reservoir and conduit function and worse booster pump function. The enhancement of LA reservoir function may be related to the frequency and total number of PAF episodes, and the increased LA conduit function may be related to the LA total emptying volume and frequency of PAF episodes.

Assessment of atrial electromechanical coupling and influential factors in nonrheumatic paroxysmal atrial fibrillation.

BACKGROUND: Sequential analysis of atrial electromechanical coupling (P-A) by Doppler tissue imaging (DTI) might provide important insight into the mechanisms of paroxysmal atrial fibrillation (PAF). HYPOTHESIS: The purpose of this study was to evaluate P-A and the dispersion of P-A, and to analyze the influential factors of P-A. METHODS: One hundred and ten patients with PAF and 87 normal controls were enrolled. Using DTI, the time intervals from the beginning of P-wave to the onset of atrioventricular ring motion related to atrial contraction were measured. RESULTS: Atrial electromechanical coupling at the interventricular septum atrioventricular annulus (P-A1), left lateral mitral annulus (P-A2) and right lateral tricuspid annulus (P-A3) in PAF group were significantly longer than those in control (p < 0.001). The difference between P-A2 and P-A1 (T1), P-A2 and P-A3 (T3) in PAF group were greater than those in control before age correction (p < 0.05). The linear regression analysis showed that the duration of PAF episodes and age were the greatest influential factors of P-A1 (r = 0.564). Left atrial anterior-posterior dimension (LAD) and age were the greatest influential factors of P-A2 (r = 0.459). The LAD was the greatest influential factors of T1 and T3 (r = 0.408, 0.542). CONCLUSIONS: The atrial electromechanical coupling was significantly longer and the dispersion of P-A at left lateral mitral annulus was greater in PAF patients. The prolongation of P-A may be related to left atrial enlargement, long episodes of PAF and aging and the dispersion of P-A at left lateral mitral annulus to LAD.

Differences in atrial electromechanical coupling and atrial volume in patients with idiopathic paroxysmal atrial fibrillation.

OBJECTIVES: The objective of the study was to evaluate the differences in atrial electromechanical coupling time and atrial volume between patients with idiopathic paroxysmal atrial fibrillation and control subjects and to investigate the influencing factors of electromechanical coupling time. METHODS AND RESULTS: We studied 46 patients with idiopathic PAF (group IPAF) and 62 control subjects (group N). Doppler tissue imaging data were performed to assess atrial electromechanical coupling.Atrial volumes were evaluated by acoustic quantification.The time intervals from the beginning of the P wave to the onset of atrial contraction motion at the interventricular septum atrioventricular annulus (P-A1), left lateral mitral annulus (P-A2) in group IPAF were significantly longer than in group N (P < 0.01). P-A2 was correlated positively with left atrial (LA) anterior-posterior dimension and the largest LA volume (r = 0.751, 0.689, P < 0.01) in the IPAF group.The longest duration of IPAF episodes was correlated with P-A2 (r = 0.652, P < 0.05). CONCLUSIONS: There is a prolongation in the atrial electromechanical coupling from the onset of the P wave to the beginning of the backward motion of the mitral annulus and interventricular septum atrioventricular annulus in patients with idiopathic PAF. This prolongation may be affected by left atrial size and the longest duration of the IPAF episodes.

Left and right atrial size and the occurrence predictors in patients with paroxysmal atrial fibrillation.

The purpose of the present study is to evaluate left and right atrial volume in patients with paroxysmal atrial fibrillation (PAF) and to select the best clinical variables to predict the occurrence of PAF. 157 patients and 106 normal subjects were enrolled. In patients with PAF, right atrial volume and dimension were all significantly greater (P<0.001 approximately 0.05). Left atrial (LA) volume were obviously higher (P<0.01) before correction for age. Atrial dilation and right atrial shape remoding are evident compared to normal controls. Patients are more prone to PAF occurrence if they have increased LA anterior-posterior diameter, greater P maximum and advancing age.