Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: A joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology.

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway.

Effect and clinical implications of the low-energy diode laser on bone cell proliferation.

Laser is a simple, noninvasive technique that has proven useful for treating damaged tissue. However, its effects on bone regeneration and the mechanisms involved are poorly understood. The objective of this study was to evaluate the effects on MG-63 cell proliferation of application of a pulsed diode laser (Ezlase) of 940 nm at low energy levels. After 24 hr of culture, osteoblasts underwent pulsed laser radiation at 0.5, 1, 1.5, and 2 W and fluences of 1-5 J. A control group was not irradiated. After the treatment, cells were incubated for 24 hr, and cell proliferation was analyzed using a spectrophotometric measure of cell respiration (MTT assay). Results were expressed as percentage proliferation versus controls. At 24-hr culture, cell proliferation was increased in laser-treated cells at intensities of 0.5, 1, and 1.5 W/cm(2) versus controls; the energy density was positively correlated with cell growth, which reached a peak at 3 J and decreased at higher fluences. The use of pulsed low-level laser with low-energy density range thus appears to exert a biostimulatory effect on bone tissue. Although the data on cell proliferation are robust, in-depth investigation is required into the effect of these irradiation doses on other cell parameters. The present findings demonstrate that laser therapy could be highly useful in tissue regeneration in different clinical settings, including nursing, physical therapy, dentistry, and traumatology.

Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.

Rectally applied antiretroviral microbicides for preexposure prophylaxis (PrEP) of HIV infection are currently in development. Since enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (Normosol-R)-in a crossover design. Nine men received each enema type in random order. Enemas were radiolabeled [(99m)Tc-diethylene triamine pentaacetic acid (DTPA)] to assess enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar enema had greater proximal colonic distribution (up to the splenic flexure) and greater luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other enemas (p<0.01). Colon biopsies also showed that only the hyperosmolar enema caused sloughing of the colonic epithelium (p<0.05). In permeability testing, the hypoosmolar enema had higher plasma (99m)Tc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar enemas, respectively. Acceptability was generally good with no clear preferences among the three enema types. The isoosmolar enema was superior or similar to the other enemas in all categories and is a good candidate for further development as a rectal microbicide vehicle.

Myocardial infarction does not preclude electrical and hemodynamic benefits of cardiac resynchronization therapy in dyssynchronous canine hearts.

BACKGROUND: Several studies suggest that patients with ischemic cardiomyopathy benefit less from cardiac resynchronization therapy. In a novel animal model of dyssynchronous ischemic cardiomyopathy, we investigated the extent to which the presence of infarction influences the short-term efficacy of cardiac resynchronization therapy. METHODS AND RESULTS: Experiments were performed in canine hearts with left bundle branch block (LBBB, n=19) and chronic myocardial infarction, created by embolization of the left anterior descending or left circumflex arteries followed by LBBB (LBBB+left anterior descending infarction [LADi; n=11] and LBBB+left circumflex infarction [LCXi; n=7], respectively). Pacing leads were positioned in the right atrium and right ventricle and at 8 sites on the left ventricular (LV) free wall. LV pump function was measured using the conductance catheter technique, and synchrony of electrical activation was measured using epicardial mapping and ECG. Average and maximal improvement in electric resynchronization and LV pump function by right ventricular+LV pacing was similar in the 3 groups; however, the site of optimal electrical and mechanical benefit was LV apical in LBBB hearts, LV midlateral in LBBB+LCXi hearts and LV basal-lateral in LBBB+LADi hearts. The best site of pacing was not the site of latest electrical activation but that providing the largest shortening of the QRS complex. During single-site LV pacing the range of atrioventricular delays yielding > or =70% of maximal hemodynamic effect was approximately 50% smaller in infarcted than noninfarcted LBBB hearts (P<0.05). CONCLUSIONS: Cardiac resynchronization therapy can improve resynchronization and LV pump function to a similar degree in infarcted and noninfarcted hearts. Optimal lead positioning and timing of LV stimulation, however, require more attention in the infarcted hearts.