Improved mitochondrial function in the hearts of sarcolipin-deficient dystrophin and utrophin double-knockout mice.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease associated with cardiomyopathy. DMD cardiomyopathy is characterized by abnormal intracellular Ca2+ homeostasis and mitochondrial dysfunction. We used dystrophin and utrophin double-knockout (mdx:utrn-/-) mice in a sarcolipin (SLN) heterozygous-knockout (sln+/-) background to examine the effect of SLN reduction on mitochondrial function in the dystrophic myocardium. Germline reduction of SLN expression in mdx:utrn-/- mice improved cardiac sarco/endoplasmic reticulum (SR) Ca2+ cycling, reduced cardiac fibrosis, and improved cardiac function. At the cellular level, reducing SLN expression prevented mitochondrial Ca2+ overload, reduced mitochondrial membrane potential loss, and improved mitochondrial function. Transmission electron microscopy of myocardial tissues and proteomic analysis of mitochondria-associated membranes showed that reducing SLN expression improved mitochondrial structure and SR-mitochondria interactions in dystrophic cardiomyocytes. These findings indicate that SLN upregulation plays a substantial role in the pathogenesis of cardiomyopathy and that reducing SLN expression has clinical implications in the treatment of DMD cardiomyopathy.

Wire countertraction for sheath placement through stenotic and tortuous veins: The "body flossing" technique.

BACKGROUND: Innominate vein stenosis and venous tortuosity are common findings during cardiac implantable electronic device upgrades or replacements and present a challenge to the implanting physician. Various techniques have been described to facilitate lead placement, including serial dilation, balloon venoplasty, and percutaneous access medial to the stenosis, each with its own benefits and risks. OBJECTIVE: The purpose of this study was to assess the feasibility, safety, and efficacy of the wire countertraction ("body flossing") technique to facilitate sheath placement through tortuous and stenotic vessels. METHODS: Patients undergoing cardiac implantable electronic device procedures requiring the body flossing technique due to inability to place vascular sheaths over the wire through stenoses or tortuosity were retrospectively analyzed. Clinical characteristics, procedural equipment, and outcomes were analyzed. RESULTS: Simultaneous countertraction was successful in all attempted cases, including 8 patients with stenoses and 2 with tortuosity. In 2 of the stenosis cases, venoplasty had previously failed. No complications occurred. CONCLUSION: Simultaneous countertraction (body flossing) is an effective tool to overcome venous stenosis and tortuosity that are amenable to wire advancement but not to vascular sheaths. It seems to be a safe and effective alternative to other techniques used in these scenarios.

High incidence of ST-T changes in women during tilt-table testing.

INTRODUCTION: We have observed electrocardiographic (ECG) changes primarily in women during tilt table testing. METHODS: We reviewed 12 lead ECGs during tilt studies between 2012 and 2016 for changes in ST segments and T waves during tilt table testing. Patients with distinctly abnormal baseline ECGs were excluded. RESULTS: Of the 180 tilt studies, 117 (65%) were in women. There were 32 patients with ECG changes during tilting. Of these, 28 (87.5%) were in women with an average age of 45years. None had a history of CAD or exertional chest pain. Echocardiograms were available in 21 of the 28 women with tilt induced ECG changes and all were normal. ECG changes during tilt table testing were found in 4/64 (6.25%) of men. The occurrence of ST-T wave changes during tilt testing was significantly higher among women compared to men, with a p value of 0.008. Of the 28 women with ECG changes during tilt, 11 had T wave inversions alone. ST segment depression alone was noted in 7 women. There were 10 women who had both ST segment depression and T wave inversions. Changes occurred immediately upon tilting in 6. In the remaining, they occurred at an average of 4.8±4min after tilting. The slight increase in heart rate in patients with ECG changes was similar to that in the patients without new ECG changes. The ECG changes were not related to the presence of syncope. CONCLUSIONS: ECG changes during the testing was observed at a relatively high incidence primarily in women. The clinical significance of these repolarization changes during tilt testing is unknown. These ECG changes during tilt testing may correlate with the high incidence of false positive ECGs in women during exercise testing but do not necessarily indicate the presence of ischemic coronary disease. Additional research is needed to explain this phenomenon.

Cardiac transplantation in African Americans: a single-center experience.

BACKGROUND: In view of limited data on the subject of graft and patient survival differences between African American (AA) and non-AA heart transplant recipients, we reviewed our experience. HYPOTHESIS: There is a higher mortality among AA recipients compared with non-AA recipients after cardiac transplantation. METHODS: The study included all AA patients who have received a heart transplant in our center since 1983. Stepwise Cox regression was used for covariates affecting the survival. The χ(2) test was employed to identify the effects of a mechanical assist device and pretransplant creatinine (Cr) on the outcomes in AA and non-AA patients. Kaplan-Meier curves were used to examine survival. RESULTS: The average survival among AA recipients was 5.4 years, compared with 12 years for the non-AA recipients, with 1-, 5-, and 10-year survival rates of 80%, 55%, and 25%, respectively. This was found to be statistically inferior to the survival probabilities of 92%, 78%, and 58% for the non-AA group (P < 0.005). Based on stepwise Cox regression, the variables such as ethnicity (P < 0.05), pretransplant Cr (P < 0.05), presence of a mechanical assist device (P < 0.005), and United Network for Organ Sharing (UNOS) status at transplant (P < 0.05) independently predicted the outcomes. Kaplan-Meier analysis of pretransplant Cr level and survival showed that the AA group did significantly worse for all Cr classes. CONCLUSIONS: There is a statistically significant difference in outcomes between AA and non-AA patients after cardiac transplantation. African American patients have decreased survival over a period of time. Pretransplant Cr, ethnicity, presence of a mechanical assist device, and UNOS status at transplantation are independent predictors of outcomes.