Cardiac computed tomography-verified right ventricular lead position and outcomes in cardiac resynchronization therapy

Journal of Interventional Cardiac Electrophysiology - To evaluate the association between different right ventricular (RV) lead positions as assessed by cardiac computed tomography (CT) and...     

Mechanism of ventricular tachycardia in a patient with double-outlet left ventricle

We report the case of ventricular tachycardia (VT) ablation procedure in a patient with history of surgically repaired double-outlet left ventricle. The electrophysiology procedure revealed a re-entry pattern between the right-ventricle to main-pulmonary-artery conduit and the tricuspid annulus. The re-entrant mechanism was most likely promoted by a fibrous remodeling of this area, related to the surgical repair. This case is the first to describe a re-entry mechanism between fixed anatomical barriers in a repaired right ventricle of a double-outlet left ventricle. A pace mapping technique was used to highlight the VT isthmus.     

Modified bypass procedure and apicoaortic conduit. Management of coronary artery disease,aortic valve stenosis and porcelain aorta

BACKGROUND: In case of severely calcified ascending aorta, modified operative strategies are required in order to avoid manipulations of the aorta and minimize subsequent cerebral vascular accidents. CASE REPORT: A 73-year-old woman, with a coronary two-vessel disease and aortic stenosis was scheduled for coronary artery bypass grafting and aortic valve replacement. Due to severed calcification of the ascending aorta including the transverse arch, neither cannulation, clamping nor incision of the aorta or its replacement was feasible. Therefore bypass operation was performed using a modified approach. After 1 month, implantation of a valved conduit between the left ventricular apex and the descending aorta through a lateral thoracotomy followed. CONCLUSION: Only in few cases the surgical treatment of a coronary artery disease in combination with left ventricular outflow tract obstruction and heavily calcified ascending aorta has been described. Undoubtedly, creation of an apicoaortic connection is today only indicated in the adult population in a small collective with multiple previous operations or porcelain aorta.     

Value of comparative genomic hybridization and fluorescence in situ hybridization for molecular diagnostics in multiple myeloma

Chromosomal abnormalities, such as 13q deletions, are emerging as important prognostic factors in multiple myeloma. Fluorescence in situ hybridization (FISH) using specific DNA probes is the technique most widely used for the determination of genomic aberrations in this disease. The utility of comparative genomic hybridization (CGH) for molecular diagnostics in plasma cell malignancies has not been systematically analysed. We investigated tumour samples of patients with multiple myeloma (n = 43) or plasma cell leukaemia (n = 3) using CGH and FISH with five DNA probes localized to chromosome bands 1p22, 6q21, 11q22-q23, 13q14 and 17p13. By CGH, the most frequent genomic changes were gains on chromosomes 1q, 9q and 11q, as well as losses on chromosomes 13q, 6q, Xp and Xq. By FISH, trisomy 11q was identified at a similar frequency to the 13q deletion (42%). Compared with FISH data, the sensitivity of CGH was 80.7% and the specificity was 97.5%. Thirty-two aberrations found by FISH were not identified by CGH, mostly as a result of the proportion of cells carrying the respective aberrations, or because of the limited spatial resolution of CGH. Our data indicate that, for clinical molecular diagnostics in multiple myeloma, FISH with a disease-specific DNA probe set is superior to CGH analysis.     

Chronic cyclooxygenase-2 inhibition does not alter blood pressure and kidney function in renovascular hypertensive rats

BACKGROUND: It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function. METHODS: Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo. RESULTS: Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment. CONCLUSIONS: Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats.     

Impact of unrelated donor status on the incidence and outcome of cytomegalovirus infections after non-myeloablative allogeneic stem cell transplantation

Little is known about the impact of cytomegalovirus (CMV) infections that occur after human leucocyte antigen (HLA)-matched unrelated donor (MUD) non-myleoablative haematopoietic stem cell transplantation (HCT). We analysed the incidence, onset and outcomes of CMV infections in 59 recipients of MUD and in 109 recipients of HLA-matched related donor (MRD) allogeneic HCT following non-myeloablative conditioning containing 2 Gy total body irradiation and fludarabine. In CMV seropositive recipients, antigenaemia occurred in 68% (MUD) and in 49% (MRD, P = 0.08); there were no differences in the maximum levels of CMV antigenaemia and the time to cessation with antiviral therapy. CMV viraemia by culture was more common in MUD compared with MRD HCT recipients in univariate analysis (26% vs. 6%, P = 0.01), however, this difference was not detectable after controlling for other factors. The rates of CMV disease in the first 100 d were similar in MUD (9%) and MRD (5%) HCT recipients. CMV disease tended to occur earlier in the MUD compared with the MRD recipients (median day 41 vs. day 80). Beyond day 100, rates of CMV disease remained similar in both cohorts (cumulative incidence: MUD 21% and MRD 14%). The 30-d and 1-year survivals after CMV disease diagnosis were not significantly different in both groups. Thus, there appeared to be a trend toward increased CMV reactivation in MUD compared with MRD non-myeloablative allogeneic HCT recipients; however, these differences did not reach statistical significance in this cohort and preemptive therapy was similarly effective in preventing CMV diseases.     

Connexins regulate calcium signaling by controlling ATP release

Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca²⁺ mobilization and was inhibited by Cl⁻ channel blockers. Calcium wave propagation also was reduced by purinergic receptor antagonists and by Cl⁻ channel blockers but insensitive to gap junction inhibitors. These observations suggest that cell-to-cell signaling associated with connexin expression results from enhanced ATP release and not, as previously believed, from an increase in intercellular coupling.     

Is serial determination of inspiratory muscle strength a useful prognostic marker in chronic heart failure?

BACKGROUND: Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown. DESIGN: Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis. METHODS: In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months. RESULTS: Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27). CONCLUSION: Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.     

Anatomically oriented right ventricular volume measurements with dynamic three-dimensional echocardiography validated by 3-Tesla magnetic resonance imaging.

OBJECTIVES: We tested a newly developed 4-dimensional (4D) right ventricular (RV) analysis method for computing RV volumes for both 3-dimensional (3D) ultrasound (US) and magnetic resonance (MR) images. BACKGROUND: Asymmetry and the anatomical complexity of the RV make accurate determination of RV shape and volume difficult. METHODS: Thirty patients, 14 with grossly normal cardiac anatomy and 16 with major congenital heart disease, were studied at the same visit with both 3D echocardiography (echo) and magnetic resonance imaging (MRI) for RV size and function. Ultrasound images were acquired on a Philips 7500 system (Philips Medical Systems, Andover, Massachusetts) with a matrix-array transducer (real-time 3D echo) with full volume sweeps from apical and subcostal views. Sagittal, 4-chamber, and coronal views were derived for contour detection (all 12 to 24 slices). The MR images were acquired with a 3-T MRI magnet with segmented cine-loop gradient echo sequences in short- and rotated long-axis views to cover the RV inflow, body, and outflow tract. The RV volumes were analyzed with the new software applicable to 3D echo MR images. RESULTS: New software aided delineation of the RV free wall, tricuspid valve, RV outflow tract, and apex on 3D echo volumes. Although there was a slightly higher variability measuring right ventricular ejection fraction (RVEF) and volumes obtained by US compared with MRI, both imaging methods showed closely correlated results. The RVEF was measured with 4% variability for US and 5% variability for MRI with a correlation coefficient of r = 0.91. The RV end-diastolic volume was measured at 70.97 +/- 15.0 ml with 3D US and at 70.06 +/- 14.8 ml with MRI (r = 0.99), end-systolic volume measured 39.8 +/- 10.4 ml with 3D US and 39.1 +/- 10.2 ml with MRI (r = 0.98). CONCLUSIONS: The new RV analysis software allowed validation of the accuracy of 4D echo RV volume data compared with MRI.