Transient elevation of high-sensitive troponin T after Cardioband implantation.

BACKGROUND: The Cardioband system enables percutaneous surgical-like direct mitral valve annuloplasty and, thereby, repair of severe functional mitral valve regurgitation (MR) in patients with advanced systolic heart failure (HF) and dilation of the left ventricular (LV) annulus. Since the device is anchored by screws in the LV annulus, limited myocardial injury is likely to occur. METHODS AND RESULTS: Five patients (Society of Thoracic Surgeons score: 2.7 ± 0.7%) with severe HF (LV ejection fraction [LVEF]: 17 ± 1%; LV end-diastolic diameter [LVEDD]: 71 ± 3 mm) were treated with the Cardioband (sizes C-F) receiving 14-17 screws in the LV annulus region. Myocardial injury was monitored by measuring high-sensitive cardiac troponin T (hsTnT) levels and by echocardiography. All patients showed significant periprocedural increase in hsTnT levels. Peak hsTnT concentration was reached between day 1 and day 6 (593 ± 141 pg/ml). None of the patients showed clinical signs of myocardial infarction, ST-segment elevation, new onset of deteriorated myocardial wall motion, or new ventricular tachycardia. hsTnT levels normalized in all patients after 14 days (hsTnT on day 0: 34 ± 6 pg/ml vs. hsTnT on day 14: 36 ± 6 pg/ml; p = 0.604). This nonischemic hsTnT kinetics was compared to a sixth patient who experienced proximal damage of the left circumflex artery (LCX) and ST-segment elevation during the Cardioband procedure, followed by immediate repair of the LCX, avoiding structural damage of the LV. CONCLUSION: Cardioband implantation is accompanied by significant elevation of hsTnT without causing structural myocardial damage or clinical symptoms such as worsening of LV function, new-onset LV regions exhibiting reduced wall motion, or ventricular tachycardia.

Peri-procedural silent cerebral infarcts after left atrial appendage occlusion.

BACKGROUND AND PURPOSE: To determine the rate of peri-interventional silent brain infarcts after left atrial appendage occlusion (LAAO). METHODS: In this prospective, uncontrolled single-center pilot study, consecutive patients with atrial fibrillation undergoing LAAO between July 2013 and January 2016 were included. The Amplatzer Cardiac Plug, WATCHMAN or Amulet device was used. A neurological examination and cranial magnetic resonance imaging (MRI) were performed within 48 h before and after the procedure. MRI was evaluated for new diffusion-weighted imaging (DWI) hyperintensities, cerebral microbleeds (CMBs) and white-matter lesions (WMLs). RESULTS: Left atrial appendage occlusion was performed in 21 patients (mean age, 73.2 ± 9.5 years). Main reasons for LAAO were previous intracerebral hemorrhage (n = 11) and major systemic bleeding (n = 6). No clinically overt stroke occurred peri-interventionally. After the intervention, one patient had a small cerebellar hyperintensity on DWI (4.8%; 95% confidence interval, 0.0-14.3) that was not present on the MRI 1 day before the procedure. Among 11 patients with available MRI just before LAAO, there were no significant changes in the number of CMBs and the severity of WMLs after LAAO. CONCLUSIONS: This study of peri-interventional MRI in LAAO suggests a low rate of silent peri-procedural infarcts in this elderly population. Confirmation in larger studies is needed.

High throughput echocardiography in conscious mice: training and primary screens.

PURPOSE: Genetic engineering techniques led to an exponential increase in the number of transgenic and knock-out mouse models. For many genetically modified mice, high throughput echocardiography is an essential part of a systematic screening workflow. Many researchers perform mouse echocardiography in conscious animals to avoid anesthesia-induced impairment of cardiac function. However, it has been controversially discussed whether mice need to be habituated to handling before their cardiac function can be assessed. The aim of this study was to test the influence of training on parameters assessed during conscious mouse echocardiography. In addition, we tested whether a simple and fast echocardiography protocol has sufficient sensitivity and specificity for primary screening. MATERIALS AND METHODS: Examined parameters include fractional shortening, heart rate and respiratory rate. A total of 139 mice were examined in this study with a total of 587 echocardiograms. 103 mice were examined on five consecutive days (with examinations on day 1 - 4 regarded as training), 36 mice were only examined on day 1 and 5. RESULTS: Fractional shortening, heart rate and respiratory rate did not show any statistically significant difference between day 1 and day 5 in both groups. The sensitivity and specificity of fractional shortening assessment for predicting a homozygote knock out genotype were 86 % and 97 %, respectively. CONCLUSION: We conclude that conscious mouse echocardiography can be performed in untrained mice. Fractional shortening measurements may suffice for correct phenotyping in a high throughput setting.

Down-regulation of CD55 and CD46 expression by anti-sense phosphorothioate oligonucleotides (S-ODNs) sensitizes tumour cells to complement attack.

Overexpression of one or more membrane-bound complement regulatory proteins (mCRPs) protects tumour cells against complement-mediated clearance by the autologous humoral immune response and is also considered as a barrier for successful immunotherapy with monoclonal anti-tumour antibodies. Neutralization of mCRPs by blocking antibodies, enzymatic removal or cytokine-mediated down-regulation has been shown to sensitize tumour cells to complement attack. In our study we applied, for the first time, anti-sense phosphorothioate oligonucleotides (S-ODNs) to knock down the expression of the mCRPs CD55 and CD46 with the aim of exploiting complement more effectively for tumour cell damage. Potent anti-sense oligonucleotides against CD55 and CD46 were identified by screening various target sequences (n = 10) for each regulator. S-ODN anti-CD55(687) reduced CD55 protein expression up to 84% and CD46 protein expression was inhibited up to 76% by S-ODN anti-CD46(85). Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed a similar reduction of the CD55 and CD46 mRNA levels, which argues for an RNAse H-dependent anti-sense mechanism. T47D, A549 and PC3 cells, representing breast, lung and prostate carcinoma, were used for functional studies. Dependent on the particular cell line, anti-sense-based inhibition of mCRP expression enhanced complement-dependent cytolysis (CDC) up to 42% for CD55 and up to 40% for CD46, and the combined inhibition of both regulators yielded further additive effects in T47D cells. C3 opsonization of CD55/CD46-deficient tumour cells was also clearly enhanced upon mCRP suppression. Due to the clinical applicability of S-ODNs, the anti-sense approach described in this study may offer an additional alternative to improve the efficacy of antibody- and complement-based cancer immunotherapy.

Three-dimensional MR coronary angiography using the navigator technique compared with conventional coronary angiography.

OBJECTIVE: We evaluated the diagnostic accuracy of three-dimensional (3D) MR coronary angiography with the navigator technique for the detection of coronary artery stenoses in comparison with that of conventional radiographic angiography. SUBJECTS AND METHODS: Thirty patients with coronary artery disease were examined with an ECG-triggered 3D fast low-angle shot sequence using retrospective respiratory gating and the navigator technique on a 1.5-T MR scanner. The data set was evaluated as a 3D view with a surface rendering technique. RESULTS: Imaging of the proximal coronary arteries was possible in all patients. The average visualized lengths of the left main, left anterior descending, left circumflex, and right coronary arteries were 1.9+/-0.5 cm (mean +/- SD), 5.2+/-2.3 cm, 4.2+/-1.9 cm, and 5.2+/-2.5 cm, respectively. Irregular breathing reduced image quality in seven of the 30 patients, making diagnosis of stenoses impossible. In the 77% of patients whose examinations resulted in high-quality images, the sensitivity and specificity for detection of significant stenoses and occlusions in all four main coronary arteries were 81% and 89%, respectively. CONCLUSION: The navigator technique allows reproducible imaging of the proximal course of coronary arteries. This technique obviates breath-hold studies, thus allowing more patients to be examined. In patients whose examinations resulted in high-quality images, significant coronary artery lesions could be seen. However, for widespread clinical use, further technical improvement is necessary to increase sensitivity and specificity.

The prevalence of congenital heart disease among the population of a metropolitan cleft lip and palate clinic.

The entire infant population of the Tufts-New England Medical Center Cleft Palate Clinic was reviewed, and the prevalence rates of congenital cardiac anomalies were calculated. The overall prevalence rate of congenital heart disease among the facial cleft clinic population was 6.7%, with a prevalence rate of 9.1% among patients with submucous cleft palate, 7.7% with congenital palato-pharyngeal incompetence, 0% with cleft lip only, 5.3% with unilateral cleft lip and palate, 12.5% with bilateral cleft lip and palate, 4.3% with cleft palate only, 13.6% with Pierre-Robin anomaly, 7.1% with cleft lip and palate and a syndrome diagnosis, 16.7% with cleft palate and a syndrome diagnosis.