Myocardial fibrosis and its relation to adverse outcome in transposition of the great arteries with a systemic right ventricle.

BACKGROUND: Myocardial dysfunction has been implicated in gradual heart failure in transposition of the great arteries (TGA) with a systemic right ventricle (RV). Fibrosis can be assessed using the extracellular volume fraction (ECV). Our aim was to measure ECV and determine its associations with clinical findings and outcomes. METHODS: We prospectively measured ECV in systemic RV subjects (either D-loop after atrial switch or L-loop) and healthy controls. T1 measurements for a single mid-ventricular short-axis plane before and 3, 7, and 15 min after gadolinium contrast were used to quantify systemic ventricular ECV. Individuals with elevated ECV were compared to those without. RESULTS: In 53 TGA subjects (age 34.6 ±â€¯10.3 years, 41% female) the mean ECV for the systemic RV (28.7 ±â€¯4.4%) was significantly higher than the left ventricle in 22 controls (26.1 ±â€¯2.8%, P = 0.0104). Those with an elevated ECV (n = 15, 28.3%) had a higher b-type natriuretic peptide (BNP) (P < 0.011) and a longer 6-min walk distance (P = 0.021), but did not differ by age, arrhythmia history, ventricular volume, function, or circulating collagen byproducts. At follow-up (median 4.4 years), those experiencing major cardiovascular endpoints (new arrhythmia, arrhythmia device, heart failure hospitalization, listing for transplantation, mechanical support, or cardiovascular death, n = 14) had a higher ECV. ECV, age, and BNP were independent predictors of cardiac events in Cox-proportional hazard models. CONCLUSIONS: Myocardial fibrosis is common in the systemic RV and associated with a higher BNP. Elevated CMR-derived ECV was associated with adverse clinical outcome. The findings suggest a role of diffuse myocardial fibrosis in clinical deterioration of the systemic RV.

Late gadolinium enhancement cardiovascular magnetic resonance of the systemic right ventricle in adults with previous atrial redirection surgery for transposition of the great arteries.

BACKGROUND: Patients treated for transposition of the great arteries by atrial redirection surgery have a right ventricle (RV) that sustains systemic pressures long term. Late RV dysfunction occurs in these patients; the reasons for this are unclear, but myocardial fibrosis may be important. Myocardial fibrosis can be visualized by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). We hypothesized that LGE would be present in the systemic RV and relate to adverse clinical features. METHODS AND RESULTS: We performed CMR on 36 consecutive adult patients (mean age, 27 years) after atrial redirection surgery for transposition of the great arteries. Late gadolinium RV enhancement was seen in 22 patients (61%) with various patterns. Patients with RV LGE were older (30 versus 22 years; P<0.001) and had increased RV end-systolic volume index (43 versus 35 mL/m2; P=0.03), decreased RV ejection fraction (57% versus 62%; P=0.02), increased QRS duration (108 versus 97 ms; P=0.01), and increased QT dispersion (93 versus 71 ms; P=0.002). The extent of LGE correlated with age (r=0.59, P<0.001) and QRS duration (r=0.67, P<0.001) and inversely with RV ejection fraction (r=-0.76, P<0.001). The incidence of documented arrhythmia and/or syncope (10 of 36) was significantly higher in the late gadolinium-positive group (9/22 versus 1/14; P=0.03). CONCLUSIONS: LGE CMR suggestive of myocardial fibrosis occurs in the systemic RV of patients after atrial redirection surgery. The extent of LGE correlates with age, ventricular dysfunction, electrophysiological parameters, and clinical events, suggesting prognostic importance that merits further investigation.

Validation of the myocardial performance index by echocardiography in mice: a noninvasive measure of left ventricular function.

BACKGROUND: The myocardial performance index (MPI) is a Doppler-based measure of left ventricular (LV) function. It is noninvasive, independent of LV shape, and does not require dimensional measurements. However, it has never been validated in mice. METHODS: A total of 29 anesthetized mice with LV pressure catheters underwent echocardiography (2-dimensional, M-mode, and Doppler) at baseline and during manipulations of beta-adrenergic tone, temperature, preload, and afterload. The maximum derivative of LV pressure with respect to time (dP/dt(max)) was compared with MPI, fractional shortening (FS), mean velocity of circumferential fiber shortening, and the FS/MPI ratio. RESULTS: MPI (baseline 0.44 +/- 0.07) correlated strongly with dP/dt(max) (R = -.779, P <.001), as did FS and mean velocity of circumferential fiber shortening. MPI differed significantly with contractility, preload, and afterload manipulation. FS/MPI showed the best correlation with dP/dt(max). CONCLUSIONS: MPI strongly correlates with dP/dt(max) over a range of hemodynamic conditions in mice. It can be used as a noninvasive index of LV function in this species.

Perinatal hypoxia causes ventricular enlargement associated with increased atrial natriuretic peptide (ANP) mRNA levels in newborn mice.

We sought to examine both the short-term and residual effects of perinatal hypoxia on ventricular mass and function of mice. We postulated that the magnitude of the ventricular hypertrophy would be determined by the timing of the exposure, be linked to augmented atrial natriuretic peptide (ANP) expression, and would persist to young adulthood. Furthermore, mice deficient in the ANP receptor type A (ANPRA) would have even greater hypertrophy. Newborns were placed in a 12% oxygen (O(2)) chamber either shortly after birth or at 8 days of age. Controls were raised in room air. After 8 or 16 days, pups were terminated and the right ventricle (RV) and left ventricle including the septum (LVS) were excised and weighed and total RNA was extracted. Hypoxia caused a reduction in body weight (BW) with an increase in right ventricle (RV) weight, rendering an increased RV to BW ratio and increased LVS/BW, albeit less. Hypertrophy was most pronounced in pups exposed to hypoxia in the first days of extrauterine life. A rapid postnatal decline in both RV and LVS ANP mRNA levels was observed in control animals, while the hypoxia elevated ANP mRNA. In mice missing the ANPRA, both ventricles were more massive than in wild type and hypoxia further augmented RV/BW and LVS/BW. In normal adult animals returned to room air after 16 days of hypoxia, RV but not LVS hypertrophy persisted in both sexes; there was an interaction between gender and the perinatal hypoxic stress on LVS dimension and perhaps on contractility. Thus perinatal hypoxia may "program" the adult mouse heart and vasculature.