Featured topics and Editors’ Picks from all of ACC’s JACC Journals ADVANCE III Trial Shows Better Outcomes With Long Detection Programming in Single Chamber ICDs In patients implanted with a single-chamber implantable cardioverter-defibrillator (ICD), programming longer detection intervals may significantly reduce therapies, shocks and all-cause mortality, according to results from the ADVANCE III Trial, presented as a Late-Breaking Clinical Trial during Heart Rhythm 2017 in Chicago, IL, and simultaneously published in JACC: Clinical Electrophysiology. Maurizio Gasparini, MD, and colleagues examined 545 patients receiving single-chamber ICDs who were randomized to long detection (30/40 intervals) or standard programming (18/24 intervals) based on device type, atrial fibrillation history and indication. During a median follow-up of 12 months, 112 therapies were delivered in 34 of 267 patients in the long detection arm compared with 257 therapies in 60 of 278 patients in the control arm, translating to a 48 percent reduction with intervention. The number of shocks delivered was 40 percent less in the long detection group. Anti-tachycardia pacing delivery rates of 22 per 100 patient-years in the long detection arm contrasted with 58 per 100 patient-years in the control arm. There were 55 percent fewer appropriate therapies in the long detection arm compared with standard programming. Inappropriate therapies were infrequent, with fewer inappropriate interventions reported in the long detection group. Syncope rates did not differ between groups but survival improved in the long detection arm. “Our results have particular gravity since the ‘standard’ intervals applied in our control arm are longer than nominal ICD settings, indicating that even further prolongation of time to delivered therapy extends the advantages of this programming strategy further,” the authors write. Gasparini M, Lunati MG, Proclemer A, et al. JACC Clin Electrophysiol 2017;May 11:[Epub ahead of print]. Do CV Risk Factors in Childhood Impact Cognition in Adulthood? The burden of cardiovascular risk factors experienced during childhood and adolescence may be associated with worse midlife cognition, independent of adulthood exposure, according to a study published May 1 in the Journal of the American College of Cardiology (JACC). Suvi Rovio, PhD, and colleagues looked at 1,901 individuals from the Cardiovascular Risk in Young Finns Study. As part of the study’s 31 year follow-up, cognitive testing was performed as well as regular measurement of blood pressure, cholesterol, triglycerides, body mass index and smoking exposure, to assess the long-term burden of each continuous risk variable. Each was defined separately for childhood (6-12 years), adolescence (12- 18 years), young adulthood (18-24 years) and early life (6-24 years). High blood pressure and high cholesterol in childhood, adolescence and young adulthood, as well as smoking in adolescence and young adulthood, were associated with worse midlife cognitive performance, especially memory and learning. Study participants with all risk factors within recommended levels between ages 6 and 24 performed better on cognitive testing than those exceeding all risk factor levels at least two-fold. In all, the difference corresponded to the effect of six years of aging. “These findings support the need for active monitoring and treatment strategies against cardiovascular risk factors from childhood,” the authors conclude. “This shouldn’t just be a matter of cognitive deficits prevention, but one of primordial prevention.” Valentin Fuster, MD, PhD, MACC, editor-in-chief of JACC, adds that “Recent evidence has demonstrated that risk factors developed in adulthood can impact cognitive dysfunction in the elderly, if they have not been corrected. The findings in this paper are important, because they show that risk factors that develop at an even younger age can have the same adverse impact.” In an accompanying editorial, Donald M. Lloyd-Jones, MD, ScM, FACC, and Norrina B. Allen, PhD, MPH, note that, “These findings extend our prior understanding on the accumulation of cardiovascular risk and cognition back into childhood and suggest that the adverse impacts on later-life health begin accruing very early in life.” Rovio SP, Pahkala K, Nevalainen J, et al. J Am Coll Cardiol 2017;69:2279-89. Do Beta-Blockers Reduce Mortality in HFrEF Patients? Beta-blockers may reduce mortality in patients with heart failure and reduced ejection fraction (HFrEF) in sinus rhythm, regardless of pretreatment heart rate, but there is no effect on mortality in patients with atrial fibrillation (AFib), according to research presented April 30 at Heart Failure 2017 in Paris, France, and simultaneously published in the Journal of the American College of Cardiology. Dipak Kotecha, PhD, and colleagues examined 14,313 patients in sinus rhythm and 3,065 patients in AFib. A higher baseline heart rate was associated with greater all-cause mortality in patients with sinus rhythm, but not in patients with AFib. Beta-blockers reduced heart rate by 11 to 12 beats per minute in both sinus rhythm and AFib. The overall hazard ratio (HR) for mortality comparing betablockers with placebo for patients in sinus rhythm was 0.73 (95 percent confidence interval [CI], 0.67-0.79; p < 0.0001) with similar benefit for all three strata of baseline heart rate. However, beta-blockers did not reduce mortality for patients in AFib, either overall (HR, 0.96, 95 percent CI, 0.81-1.12; p = 0.58) or for any baseline heart rate stratum. At an interim visit, the heart rate achieved in sinus rhythm was more strongly associated with mortality than the change in heart rate from baseline. The lowest mortality in sinus rhythm was observed in patients who attained lower heart rates after beta-blocker therapy. Neither attained nor change in heart rate was associated with survival in patients with AFib. The authors were not able to determine whether clinicians should strive to achieve a target heart rate or a target dose of beta-blocker. “Ultimately, heart rate and prescribed beta-blocker dose are intimately related; one is a surrogate for the other although the relationship may be complicated by other factors such as genetic variations in beta-blocker response and drug metabolism,” the authors write. “Our observation of dose-related differences in mortality in patients assigned to placebo clearly demonstrates that it is unsafe to make strong inference from any analysis of a post-randomization variable such as dose. Dose achieved is itself an outcome, affected by confounding patient factors, adherence, physician preferences and bias, including the perceived risk of adverse outcomes,” they conclude. Kotecha D, Flather MD, Altman DG, et al. J Am Coll Cardiol 2017;April 30:[Epub ahead of print]. Reduced Radiation Exposure Seen in SPECT MPI Patients Recent efforts to reduce radiation exposure for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) appear to be successful, according to research presented May 7 at the International Conference on Nuclear Cardiology and Cardiac CT in Vienna, Austria, and simultaneously published in JACC: Cardiovascular Imaging. Randall C. Thompson, MD, FACC, and colleagues examined data from SPECT MPI studies performed at the Saint Luke’s Mid America Heart Institute nuclear cardiology laboratories from January 2009 to Sept. 2016 (n = 18,162). In 2009, all studies used large field of view (FOV) Anger cameras. By early 2011, Tl-201 protocols were eliminated. New camera models equipped with advanced post-processing software replaced older generation large FOV cameras between spring 2010 and fall 2012. Over that time, protocols designed to minimize radiotracer were employed and low-dose stress-first became a default protocol for most patients. After the elimination of Tl-201 and before the widespread use of new camera technologies, the mean effective dose decreased from 17.9 mSv in 2009 to 12.1 mSv in 2016. Since the fall of 2012, the mean effective dose of the studies conducted on small FOV cameras with APPS was 5.6 mSv, and it was 2.8 mSv in the studies performed on CZT cameras. Over 69 percent of MPI studies were performed using low-dose, stress-only imaging. Mean body mass index (BMI) and mean effective dose were much higher for the patients imaged on large FOV cameras since 2014. Over the course of the study, the overall effective dose decreased 60 percent and the median effective dose decreased 76 percent. From 2014 to 2016, the mean dose of radiotracer rose slightly, as did mean BMI. “This study demonstrates the compelling impact of a comprehensive radiation reduction strategy in a large nuclear cardiology laboratory network,” the authors write. “The data presented here demonstrate that adoption of widely available hardware and software options, and implementation of stress-first/stress-only protocols are practical in real-world daily practice and can result in very low radiation exposures for SPECT MPI.” Thompson RC, O’Keefe JH, McGhie, AI, et al. JACC Cardiovasc Imaging 2017;May 6:[Epub ahead of print]. Communicating Leadless Pacemakers and S-ICD: Preclinical Evaluation Appropriate single-chamber pacemaker functionality, successful wireless device-device communication and anti-tachycardia pacing (ATP) delivery by a leadless pacemaker commanded by an implanted subcutaneous implantable cardioverterdefibrillator (S-ICD) were demonstrated in a preclinical study presented May 12 during Heart Rhythm 2017 in Chicago, IL, and simultaneously published in JACC: Clinical Electrophysiology. Fleur V. Y. Tjong, MD, and colleagues evaluated the combined modular cardiac rhythm management (CRM) therapy system of leadless pacemaker and S-ICD prototypes in 39 animals, in acute and chronic experiments. Leadless pacemaker bradycardia pacing functionality was assessed. The mean pacing threshold, R-wave amplitude and impedance at implant were 0.53 ± 0.42 V at 0.5 msec, 19.9 ± 9.9 mV and 727 ±193 Ω, respectively. S-ICD heart rhythm discrimination was correct during intrinsic and leadless pacemaker pacing above the intrinsic rate and did not result in over-sensing. Unidirectional device-device communication from the S-ICD to the leadless pacemaker via conductive communication was successful in 306 of 309 communication attempts in the dorsal position of the animals. All ATP requests triggered by the S-ICD and received by the leadless pacemaker resulted in ATP delivery. There was a small increase in pacing threshold (p < 0.001) and decrease in R-wave amplitude (p = 0.001) and impedance (p = 0.04) between baseline and 90 days of follow-up. The chronic device-device communication success was 100 percent and all communication signals were successfully translated into ATP delivery by the leadless pacemaker. The first-in-man trials with a validated and verified modular CRM system are planned and will combine leadless pacemaker and ICD therapy in a coordinated fashion. Tjong FVY, Brouwer TF, Koop B, et al. JACC Clin Electrophysiol 2017;May 12:[Epub ahead of print].
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