Myocardial Fibrosis as a Predictor of Sudden Death in Patients With Coronary Artery Disease

BackgroundThe “gray zone” of myocardial fibrosis (GZF) on cardiovascular magnetic resonance may be a substrate for ventricular arrhythmias (VAs).ObjectivesThe purpose of this study was to determine whether GZF predicts sudden cardiac death (SCD) and VAs (ventricular fibrillation or sustained ventricular tachycardia) in patients with coronary artery disease (CAD) and a wide range of left ventricular ejection fractions (LVEFs).MethodsIn this retrospective study of CAD patients, the presence of myocardial fibrosis on visual assessment (MF_VA) and GZF mass in patients with MF_VA were assessed in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs.ResultsAmong 979 patients (mean age [± SD]: 65.8 ± 12.3 years), 29 (2.96%) experienced SCD and 80 (8.17%) met the arrhythmic endpoint over median 5.82 years (interquartile range: 4.1 to 7.3 years). In the whole cohort, MF_VA was strongly associated with SCD (hazard ratio: 10.1; 95% confidence interval [CI]: 1.42 to 1,278.9) and the arrhythmic endpoint (hazard ratio: 28.0; 95% CI: 4.07 to 3,525.4). In competing risks analyses, associations between LVEF <35% and SCD (subdistribution hazard ratio [sHR]: 2.99; 95% CI: 1.42 to 6.31) and the arrhythmic endpoint (sHR: 4.71; 95% CI: 2.97 to 7.47) were weaker. In competing risk analyses of the MF_VA subcohort (n = 832), GZF using the 3SD method (GZF_3SD) >5.0 g was strongly associated with SCD (sHR: 10.8; 95% CI: 3.74 to 30.9) and the arrhythmic endpoint (sHR: 7.40; 95% CI: 4.29 to 12.8). Associations between LVEF <35% and SCD (sHR: 2.62; 95% CI: 1.24 to 5.52) and the arrhythmic endpoint (sHR: 4.14; 95% CI: 2.61 to 6.57) were weaker.ConclusionsIn CAD patients, MF_VA plus quantified GZF_3SD mass was more strongly associated with SCD and VAs than LVEF. In selecting patients for implantable cardioverter-defibrillators, assessment of MF_VA followed by quantification of GZF_3SD mass may be preferable to LVEF.     

Intraventricular dyssynchrony predicts mortality and morbidity after cardiac resynchronization therapy: a study using cardiovascular magnetic resonance tissue synchronization imaging.

OBJECTIVES: We aimed to assess a novel measure of left ventricular (LV) dyssynchrony, a cardiovascular magnetic resonance-tissue synchronization index (CMR-TSI), in patients with heart failure (HF). A further aim was to determine whether CMR-TSI predicts mortality and major cardiovascular events (MCE) after cardiac resynchronization therapy (CRT). BACKGROUND: Cardiac dyssynchrony is a predictor of mortality in patients with HF. The unparalleled spatial resolution of CMR may render CMR-TSI a predictor of clinical benefit after CRT. METHODS: In substudy A, CMR-TSI was assessed in 66 patients with HF (age 60.8 +/- 10.8 years, LV ejection fraction 23.9 +/- 12.1% [mean +/- SD]) and 20 age-matched control subjects. In substudy B, CMR-TSI was assessed in relation to clinical events in 77 patients with HF and with a QRS > or =120 ms undergoing CRT. RESULTS: In analysis A, CMR-TSI was higher in patients with HF and a QRS <120 ms (79.5 +/- 31.2 ms, p = 0.0003) and in those with a QRS > or =120 ms (105.9 +/- 55.8 ms, p < 0.0001) than in control subjects (21.2 +/- 8.1 ms). In analysis B, a CMR-TSI > or =110 ms emerged as an independent predictor of the composite end points of death or unplanned hospitalization for MCE (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.51 to 4.34, p = 0.0002) or death from any cause or unplanned hospitalization for HF (HR 2.15; 95% CI 1.23 to 4.14, p = 0.0060) as well as death from any cause (HR: 2.6; 95% CI 1.29 to 6.73, p = 0.0061) and cardiovascular death (HR 3.82; 95% CI 1.63 to 16.5, p = 0.0007) over a mean follow-up of 764 days. CONCLUSIONS: Myocardial dyssynchrony assessed by CMR-TSI is a powerful independent predictor of mortality and morbidity after CRT.     

Interaction between nitric oxide and endogenous vasoconstrictors in control of renal blood flow

The level of renal blood flow (RBF) is controlled by opposing vasoconstrictor and vasodilator influences. In a recent investigation in normotensive dogs, we found that combined blockade of endothelin type A (ET(A)) receptors and angiotensin II formation induces marked increases in RBF that were much larger than the effects of blocking either system alone. The aim of the present study was to determine the contribution of nitric oxide (NO) to this vasodilator response. Experiments were made in 6 conscious, chronically instrumented dogs subjected to 5 different experimental treatments on separate days. Blockade of ET(A) receptors alone by the selective antagonist LU 135252 had only minor effects on RBF compared with time-control experiments. Additional blockade of angiotensin II formation by angiotensin-converting enzyme inhibition with trandolaprilat caused a substantial increase of RBF by approximately 50%. This vasodilation was entirely suppressed when NO formation was prevented by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester HCl. However, when during NO synthase inhibition renal vascular NO concentrations were clamped at control levels by infusing the NO donor S-nitroso-N-acetyl-D, L-penicillamine, the vasodilator response to combined blockade of ET(A) receptors and angiotensin II formation was completely restored (DeltaRBF approximately 60%). These results indicate that the vasodilation after combined ET(A) receptor blockade and angiotensin-converting enzyme inhibition is not mediated by an increase in NO release but results from the unmasking of the tonic influence that is normally exerted by constitutively released NO. Accordingly, the tonic activity of endothelial NO synthase appears to be of major importance in the physiological regulation of renal vascular resistance by determining the vasomotor responses to endothelin and angiotensin II.     

Infantile colic, prolonged crying and maternal postnatal depression

Aim:  To study if infant crying is associated with maternal postnatal depression.
Methods:  Data from 1015 mothers and their children participating in a prospective European multicentre study were analysed. Infantile colic and prolonged crying were defined as excessive crying as reported by the mothers 2 and 6 months after delivery, and at the same time the mothers completed the Edinburgh Postnatal Depression Scale (EPDS).
Results:  In cross-sectional analyses, infant crying was associated with high EPDS scores both 2 (OR: 4.4; 95% CI: 2.4–8.2) and 6 months postpartum (OR: 10.8; 95% CI: 4.3–26.9). More than one-third of the others of infants with prolonged crying had high EPDS scores 6 months postpartum. Longitudinal analyses showed that mothers of infants with colic had increased odds of having high EPDS scores 6 months after delivery even if crying had resolved (OR: 3.7; 95% CI: 1.4–10.1).
Conclusion: Both infantile colic and prolonged crying were associated with high maternal depression scores. Most noteworthy, infantile colic at 2 months of age was associated with high maternal depression scores
4 months later.     

Treatment of hypercholesterolemia in children and adolescents

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma Neurotensin: Lack of a Differentiation and Tumor Marker in Children with Neuroblastoma

Neurotensin is a tridecapeptide with changing receptor expression in central and peripheral neural cells during ontogeny suggesting its potential use as a differentiation and tumor marker in neuroectodermal malignancies. We investigated the neurotensin levels in plasma samples of 58 patients with neuroblastoma using a sensitive radioimmunoassay. Elevated levels were found only in one stage III and in one stage IVs patient, while the neurotensin concentrations of 56 patients were in the range of control children. We conclude that plasma neurotensin reflects neither the differentiation nor the tumor status in children with neuroblastoma.     

Three-axis ellipsoidal fitting of videokeratoscopic height data after penetrating keratoplasty

PURPOSE: After penetrating keratoplasty corneal topography tends to be irregular and the fitting of spectacle glasses or contact lenses may be difficult. The purpose of this study was to demonstrate a mathematical method for approximation of discrete corneal topography height data with an ellipsoid for better appreciation of the clinical outcome after PK. PATIENTS AND METHODS: In 50 eyes (30 keratoconus, 20 Fuchs' dystrophy) penetrating keratoplasty was performed using nonmechanical trephination with the excimer laser 193 nm. Main outcome measures were objective corneal astigmatism (regular keratometry, corneal topography (TMS-1)), subjective refraction and best-corrected visual acuity (VA) in a fixed postoperative gate 3 and 12 month postoperatively and after suture removal. An approximation algorithm was applied for fitting a general ellipsoidal surface (not rotationally symmetric) to raw corneal topography height data. A set of parameters (meridional power, axis and asphericity) were calculated. The root mean square error (RMS) was determined between raw topography power data and the ellipsoidal model surface within an apical distance of 3 mm. The cylinder of subjective refraction was correlated with the keratometric readings, the Simulated Keratometry (SimK) of the topography system and the respective parameters of the model surface. RESULTS: The amount of the SimK cylinder yielded higher values than keratometry and the ellipsoidal fit; subjective refraction yielded the lowest value at each follow-up interval. The ellipsoidal fit showed the best correlation to the refractive cylinder at all follow-up stages (p = 0.04 at 3, p = 0.01 at 12 months and p = 0.002 after suture removal). The axis of the best ellipsoidal fit showed a significant correlation with the axis of the refractive cylinder at all follow-up intervals (p = 0.02 at 3 months, p = 0.01 before suture removal and p = 0.002 after suture removal). The axis of the keratometric cylinder showed a mild correlation at all follow-up examinations (p = 0.05 at 3 months, p = 0.02 before suture removal and p = 0.04 after suture). The cylinder of the topographic modeling system, however, showed a significant correlation with the refractive cylinder axis only after suture removal (p = 0.04). The paracentral corneal power of SimK (45.9D at 3 months, 44.4D at 12 months and 43.0D after suture removal) exceeded the respective values of conventional keratometry (43.1D at 3 months, 42.9D at 12 months and 41.7D after suture removal) and the ellipsoidal fit (43.3D at 3 months, 43.0D at 12 months and 41.8D after suture removal). The corneal asphericity from the ellipsoidal fit reached an approximately spherical shape in radial direction (A = 1.0) in the initial time period after penetrating keratoplasty, remained stable before suture removal and decreased significantly (p = 0.02) to a final value of A = 0.86 indicating a (normal) prolate shape of the cornea. The approximation error between the raw corneal topography height data and the best ellipsoidal fit model surface was nearly unchanged before suture removal (1.8 +/- 0.7 microm at 3 months and 1.9 +/- 1.1 microm at 12 months, p = 0.30) and decreased significantly to the examination after suture removal (0.9 +/- 0.5 microm, p = 0.01). CONCLUSIONS: The approximation of corneal topography height data with an ellipsoidal model surface renders reconstruction of clinically relevant corneal topography parameters including corneal asphericity. Even in markedly irregular corneal surfaces, such as after PK, the correlation of amount/axis of refractive cylinder with the model surface parameters is more accurate than with respective SimK values of corneal topography analysis.     

Superficial corneal effects of experimental nonmechanical penetrating keratoplasty using a Q-switched Er:YAG laser

PURPOSE: To assess thermal effects of Q-switched Er:YAG laser trephination to corneal epithelium and superficial stroma using different mask types and materials for experimental penetrating keratoplasty. METHODS: Laser trephination was performed in 20 freshly-enucleated porcine eyes (repetition rate 5 Hz, pulse energy 65 mJ, spot size 0.7 mm). We used flat, open-metal and ceramic masks for donor and recipient trephination placed directly onto the corneal surface. Main outcome measures as assessed by light microscopy after PAS staining of 8-microm paraffin sections included: extension of tissue thermal damage at the cut edge in the superficial and basal epithelial layers, the basement membrane and subepithelial stroma, and depth and width of epithelial/stromal involvement in the area of the donor mask contact. RESULTS: The thermal damage in the superficial epithelium was more pronounced in donor (mean extension 61.6 +/- 15.6 microm) than in recipient (29.4 +/- 24.9 microm, p= 0.05) trephination. In donor trephination, thermal damage zone of the superficial epithelial layer was significantly smaller with ceramic than with metal masks (21.0 +/- 23.0 versus 61.6 +/- 15.6 microm, p= 0.014). In contrast, differences at basal epithelial layer (p= 0.44), basement membrane (p= 0.79), and subepithelial stroma (p= 0.2) were not statistically significant. Superficial donor involvement of the cornea adjacent to the paracentral donor mask contact zone was seen neither with ceramic nor with metal masks. CONCLUSION: Superficial corneal alterations adjacent to the mask-cornea contact zone may be minimized by using the Er:YAG laser in a Q-switched mode. Ceramic masks, in contrast to metal masks, further reduce superficial thermal alterations at the cut edge.