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ObjectivesTo assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between OSA severity and leptin levels differs depending on obesity level.MethodsCross-sectional study of 452 untreated obstructive sleep apnea (OSA) patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±SD), BMI 32.7±5.3 kg/m2 and apnea-hypopnea index (AHI) 40.2 ± 16.1 events/hour. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed as well as fasting serum morning leptin levels measured.ResultsLeptin levels were more highly correlated with body mass index (BMI), total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI<30, BMI 30–35 and BMI>35 kg/m2). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (p=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199).ConclusionObesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.

Background-Substrate-based mapping for ventricular tachycardia (VT) ablation is hampered by its inability to determine critical sites of the VT circuit. We hypothesized that those potentials, which delay with a decremental extrastimulus (decrement evoked potentials or DEEPs), are more likely to colocalize with the diastolic pathways of VT circuits. Methods and Results-DEEPs were identified in intraoperative left ventricular maps from 6 patients with ischemic cardiomyopathy (total 9 VTs) and were compared with late potential (LP) and activation maps of the diastolic pathway for each VT. Mathematical modeling was also used to further validate and elucidate the mechanisms of DEEP mapping. All patients demonstrated regions of DEEPs and LPs. The mean endocardial surface area of these potentials was 18±4% and 21±6%, respectively (P=0.13). The mean sensitivity for identifying the diastolic pathway in VT was 50±23% for DEEPs and 36±32% for LPs (P=0.31). The mean specificity was 43±23% versus 20±8% for DEEP and LP mapping, respectively (P=0.031). The electrograms that displayed the greatest decrement in each case had a sensitivity and specificity for the VT isthmus of 29±10% and 95±1%, respectively. Mathematical modeling studies recapitulated DEEPs at the VT isthmus and demonstrated their role in VT initiation with a critical degree of decrement. Conclusions-In this preliminary study, DEEP mapping was more specific than LP mapping for identifying the critical targets of VT ablation. The mechanism of DEEPs relates to conduction velocity restitution magnified by zigzag conduction within scar channels.

Summary Acute myeloid leukaemia (AML) causes life‐threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two‐thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti‐AML therapies that do not suppress haemopoiesis. Our laboratory studies showed combined Bezafibrate and Medroxyprogesterone acetate (BaP) had activity against AML without toxicity to normal stem cells. Here we report the safety and efficacy of BaP in 20 patients (19 AML, 1 high‐risk myelodysplasia) for whom intensive chemotherapy was not an option. No patient exhibited haematological toxicity from BaP. Eleven patients took BaP alone for >4 weeks. One reverted from high risk myelodysplasia and remains transfusion independent after 201 weeks of therapy. Three AML patients gained major haematological improvements for 22–30 weeks; in one, marrow was available to document a partial AML response. Thus, this trial indicates that BaP therapy has potential for treatment of elderly and relapsed AML.

T he therapeutic potential of renal denervation (RDN) for cardiac arrhythmias was previously explored, yielding case reports and small case series that suggested RDN may be an effective adjunctive treatment in addition to medication and cardiac ablation for patients with ventricular tachycardia (VT) storm and atrial fibrillation.1-5 These promising results call for large-scale, well-controlled trials and detailed mechanistic evaluations. However, findings of the SYMPLICITY HTN-3 study (Renal Denervation in Patients With Uncontrolled Hypertension) have raised grave concerns over the benefits from RDN therapy for hypertension. 4 Hence, although RDN-based treatments are being developed for arrhythmias, it is important to reassess and confirm the antiarrhythmic potential of RDN in experiments designed to clearly demonstrate the impacts on cardiac electrophysiology. More importantly, the mechanistic basis of any antiarrhythmic effects should also be determined. See Editorial by Koruth and DukkipatiRDN has been shown to attenuate elevations in left ventricular end-diastolic pressure, suppress spontaneous premature beats, and reduce the incidence of ventricular fibrillation (VF) immediately post-acute coronary occlusion in pigs.6 RDN was also shown to reduce the incidence of ventricular arrhythmias (VAs) immediately after coronary occlusion in a similar acute canine model, in which RDN prolonged the ventricular effective refractory period (ERP) and the ventricular action potential duration, as well as decreased action potential duration dispersion. Although RDN is known to reduce renal sympathetic activity Background-The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. Methods and Results-Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (P=0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus t...

LDVF in human hearts is characterized by focal endocardial activity with mid-myocardial wave break and not by re-entry. This arrhythmia is modulated by rapid activations in early VF that lead to spontaneous Purkinje fiber activity.

Background The association between OSA and hypertension by race/ethnicity has not been well characterized in a national sample. Subjects Adult participants in the 2007–2008 National Health and Nutrition Examination Survey. Methods We reviewed self-reports of sleep apnea diagnosis, snorting, gasping or stopping breathing during sleep and snoring to derive whether OSA was probable (pOSA). Multivariable logistic regression determined whether pOSA predicted hypertension in the cohort, and BMI and ethno-racial strata. Results pOSA predicted hypertension in several groups: 1) Within BMI strata, there was a significant association among overweight individuals [OR (95% CI) =1.82 (1.26–2.62)]; 2) In race/ethnicity subgroups, the association was significant among Hispanic/Latinos [OR (95% CI) =1.69 (1.13, 2.53)] and whites [OR (95% CI) =1.40 (1.07, 1.84)]; 3) In models stratified by both race/ethnicity and weight, pOSA predicted hypertension among overweight Black/African Americans [OR (95% CI) =4.74 (1.86–12.03)], overweight whites [OR (95% CI) =1.65 (1.06, 2.57)], and obese Hispanic/Latino participants [OR (95% CI) =2.01 (1.16, 3.49)]. Conclusions A simple, self-report tool for OSA was strongly associated with hypertension, and may serve as a potential future opportunity for OSA diagnosis.