Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype.

[Figure: see text].

Midwinter Arctic leads form and dissipate low clouds.

Leads are a key feature of the Arctic ice pack during the winter owing to their substantial contribution to the surface energy balance. According to the present understanding, enhanced heat and moisture fluxes from high lead concentrations tend to produce more boundary layer clouds. However, described here in our composite analyses of diverse surface- and satellite-based observations, we find that abundant boundary layer clouds are associated with low lead flux periods, while fewer boundary layer clouds are observed for high lead flux periods. Motivated by these counterintuitive results, we conducted three-dimensional cloud-resolving simulations to investigate the underlying physics. We find that newly frozen leads with large sensible heat flux but low latent heat flux tend to dissipate low clouds. This finding indicates that the observed high lead fractions likely consist of mostly newly frozen leads that reduce any pre-existing low-level cloudiness, which in turn decreases downwelling infrared flux and accelerates the freezing of sea ice.

Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined HF Population: The GENETIC-AF Trial.

OBJECTIVES: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF). BACKGROUND: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta1-adrenergic receptor (ADRB1) Arg389Arg genotype. METHODS: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period. RESULTS: The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011). CONCLUSIONS: Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.

Improved Dosing and Administration of Rivaroxaban when Prescribed by a Cardiologist.

Rivaroxaban is a direct oral anticoagulant (DOAC) indicated to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). A discrepancy exists between the recommended dosage and real-world use of DOACs, especially rivaroxaban, thus putting patients at risk of thromboembolic events. METHODS: This retrospective study assessed real-world prescribing and patient adherence to dietary requirements during use of rivaroxaban in 116 patients with AF. Associations between prescriber specialty and the correct dosing and administration were assessed using the Chi-Square test. RESULTS: Most rivaroxaban prescriptions were ordered by cardiologists (50.9%). Sixty-nine patients (59.5%) were taking the right dose at the correct time with an adequate meal. Of the 47 (40.5%) taking rivaroxaban incorrectly, 39 (33.6%) had not been administered an adequate meal and eight (6.9%) were not prescribed the correct dose. Compared with other prescribers, patients were most likely to be taking the correct dose and administration when prescribed by cardiologists (72.9% versus 45.6%; p=0.003). Patients were least likely to be taking the correct dose and administration when prescribed by primary care providers (44.4% versus 69.0%; p=0.009). This difference was driven by patients who did not take the treatment with an adequate meal. CONCLUSION: Inappropriate prescribing, administration and non-adherence to DOACs can have devastating consequences. This highlights the importance of formal systematic education of patients prescribed DOACs across the whole health system. Future studies are warranted to explore the impact of non-adherence to rivaroxaban dietary requirements on clinical outcomes.

Effects of the HEART Camp Trial on Adherence to Exercise in Patients With Heart Failure.

BACKGROUND: Few exercise training studies in patients with heart failure (HF) report adherence to guideline-recommended 150 minutes of moderate-intensity exercise per week, and no studies have focused on a primary outcome of adherence. METHODS AND RESULTS: This randomized controlled trial evaluated the effect of a multicomponent intervention, Heart Failure Exercise and Resistance Training (HEART) Camp, on adherence to exercise (after 6, 12, and 18 months) compared with an enhanced usual care (EUC) group. Patients (n = 204) were 55.4% male, overall average age was 60.4 years, and 47.5% were nonwhite. The HEART Camp group had significantly greater adherence at 12 (42%) and 18 (35%) months compared with the EUC group (28% and 19%, respectively). No significant difference (P > .05) was found at 6 months. The treatment effect did not differ based on patient's age, race, gender, marital status, type of HF (preserved or reduced ejection fraction) or New York Heart Association functional class. Left ventricular ejection fraction (LVEF) significantly moderated the treatment effect, with greater adherence at higher LVEF. CONCLUSIONS: The multicomponent HEART Camp intervention showed efficacy with significant effects at 12 months and 18 months. Adherence levels remained modest, indicating a need for additional research to address methods and strategies to promote adherence to exercise in patients with HF.

Effects of Exercise Training versus Attention on Plasma B-type Natriuretic Peptide, 6-Minute Walk Test and Quality of Life in Individuals with Heart Failure.

PURPOSE: The purpose of this study was to compare an Exercise Training Group (EX) with an Attention-Control Group (AT-C) to more specifically assess the impact of exercise training on individuals with heart failure (HF). METHODS: Forty-two individuals with HF were randomized to AT-C or EX that met with the same frequency and format of investigator interaction. Baseline, 12- and 24-week measurements of B-type naturetic peptide (BNP), 6-minute walk test (6-MWT), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) were obtained. RESULTS: BNP tended to increase in the AT-C while remaining stable in the EX over time. A clinically significant increase in 6-MWT was demonstrated by the EX but not the AT-C. The EX achieved a clinically significant change on the KCCQ at 12 weeks, with further improvement by 24 weeks, while the AT-C demonstrated a clinically significant change at 24 weeks. CONCLUSIONS: Attention alone was inadequate to positively impact BNP levels or 6-MWT distances, but did have a positive impact on quality of life after 24 weeks. Although exercise offers enhanced benefits, individuals with HF unable to participate in an exercise program may still gain quality of life benefits from participation in a peer-support group that discusses topics pertinent to HF.

Relationship of resting B-type natriuretic peptide level to cardiac work and total physical work capacity in heart failure patients.

PURPOSE: Plasma B-type natriuretic peptide (BNP) levels obtained at rest have been previously shown to be correlated with the global functional capacity measures of peak oxygen uptake (V(O(2peak))) and the minute ventilation/carbon dioxide (VE/V(O(2))) slope. The purpose of this study was to assess the relationship of the plasma BNP level to the rate-pressure product (RPP) as an indicator of central or cardiac work capacity. METHODS: Twenty-two subjects (12 men), mean age 57 +/- 12 years, diagnosed with heart failure (8 ischemic/14 nonischemic) were recruited. All subjects were stable on optimal medical therapy for at least 1 month. Blood samples for BNP level analysis were obtained at rest. Subjects underwent a symptom-limited treadmill exercise test using a ramping protocol while V(O(2)), heart rate (HR), and blood pressure (BP) were monitored. Correlation analyses were conducted to assess the relationship of BNP level to RPP level, V(O(2peak), VE/V(O(2)) slope, end-tidal CO(2) pressure (P(ET)CO(2)), and left ventricular ejection fraction (LVEF). RESULTS: Resting BNP levels were significantly correlated with RPP levels (r = -0.69). The BNP level and the RPP level were correlated with V(O(2peak)) (r = -0.63 and r = 0.66, respectively) and VE/V(O(2)) slope (r = 0.53 and r = -0.54, respectively). The RPP level but not the BNP level was correlated with P(ET)CO(2) (r = 0.57). Neither BNP nor RPP levels were well correlated with LVEF (r = -0.26 and r = 0.14, respectively). DISCUSSION: The results of this study suggest that resting plasma BNP level may be a useful clinical measure for evaluating both global functional capacity and myocardial specific work capacity in individuals with heart failure.

Low-dose oral enoximone enhances the ability to wean patients with ultra-advanced heart failure from intravenous inotropic support: results of the oral enoximone in intravenous inotrope-dependent subjects trial.

BACKGROUND: We determined whether low-dose oral enoximone could wean patients with ultra-advanced heart failure (UA-HF) from intravenous (i.v.) inotropic support. Chronic parenteral inotropic therapy in UA-HF is costly and requires an indwelling catheter. An effective and safe oral inotrope would have value. METHODS: In this placebo-controlled study, 201 subjects with UA-HF requiring i.v. inotropic therapy were randomized to enoximone or placebo. Subjects receiving intermittent i.v. inotropes were administered study medication of 25 or 50 mg 3 times a day (tid). Subjects receiving continuous i.v. inotropes were administered 50 or 75 mg tid for 1 week, which was reduced to 25 or 50 mg tid. The ability of subjects to remain alive and free of inotropic therapy was assessed for up to 182 days. RESULTS: Thirty days after weaning, 51 (51%) subjects on placebo and 62 (61.4%) subjects in the enoximone group were alive and free of i.v. inotropic therapy (unadjusted primary end point P = 0.14, adjusted for etiology P = .17). At 60 days, the wean rate was 30% in the placebo group and 46.5% in the enoximone group (unadjusted P = .016) Kaplan-Meier curves demonstrated a trend toward a decrease in the time to death or reinitiation of i.v. inotropic therapy over the 182-day study period (hazard ratio 0.76 [95% CI 0.55-1.04]) and a reduction at 60 days (0.62 [95% CI 0.43-0.89], P = .009) and 90 days (0.69 [95% CI 0.49-0.97], P = .031) after weaning in the enoximone group. CONCLUSIONS: Although there was no benefit over placebo in weaning patients from i.v. inotropes from 0 to 30 days, the EMOTE data suggest that low-dose oral enoximone can be used to wean a modest percentage of subjects from i.v. inotropic support for up to 90 days after initiation of therapy.

Clustering of randomly advected low-inertia particles: a solvable model.

Measurements and simulations indicate that the particle-pair radial distribution function in isotropic turbulence is a power law in a range of length scales below the Kolmogorov scale for Stokes number St<<1. In this range, the exponent is proportional to St1St2 for unlike particles (1 and 2) in a bidispersion, hence St2 for a monodispersion. Here, this result is derived from a model of particle response to random advection. The analysis generalizes a geometrical interpretation of clustering to polydispersions and suggests an economical Monte Carlo simulation method.

Left ventricular assist device as destination for patients undergoing intravenous inotropic therapy: a subset analysis from REMATCH (Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure).

BACKGROUND: Left ventricular assist devices (LVADs) have improved survival in patients with end-stage heart failure. Compared with previous trials, the Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure (REMATCH) trial enrolled patients with more advanced heart failure and high prevalence of intravenous inotropic therapy. This study analyzes, on a post hoc basis, outcomes in patients undergoing inotropic infusions at randomization. METHODS AND RESULTS: Of 129 patients randomized, 91 were receiving intravenous inotropic therapy at randomization to LVAD or optimal medical management (OMM). Mean systolic pressure was 100 versus 107 mm Hg in those not receiving inotropes, serum sodium was 134 versus 137 mEq/L, and left ventricular ejection fraction was 17% for both groups. LVADs improved survival throughout follow-up for patients undergoing baseline inotropic infusions (P=0.0014); for the LVAD group versus the OMM group, respectively, 6-month survival was 60% versus 39%, 1-year survival rates were 49% versus 24%, and 2-year survival rates were 28% versus 11%. For 38 patients not undergoing inotropic infusions, 6-month survival was 61% for those with LVADs and 67% for those with OMM, whereas 1-year rates were 57% and 40%, respectively (P=0.55). Quality-of-life scores for survivors improved. Median days out of hospital for patients on inotropic therapy at randomization were 255 with LVAD and 105 with OMM. CONCLUSIONS: Despite severe compromise, patients undergoing inotropic infusions at randomization derived major LVAD survival benefit with improved quality of life. Patients not undergoing inotropic infusions had higher survival rates both with and without LVAD, but differences did not reach significance. Future studies should prespecify analyses of inotropic and other therapies to determine how disease severity and parallel medical treatment influence the benefits offered by mechanical circulatory support.