Greater Reduction In Heart Rate Research Articles

A Comprehensive Analysis of Conventional Acupuncture and Pharmacological Approaches for Cardiac Arrhythmias: An Umbrella Review.

With a global incidence of approximately 3.4% and an annual mortality rate of 3.7 million, cardiac arrhythmias (CAs) are a pressing global health issue. Their increasing prevalence, especially among older people, is intensifying the challenge for health care systems worldwide. This study aims to compare the safety and effectiveness of acupuncture and pharmacological treatments for CAs, addressing critical gaps in understanding optimal therapeutic approaches. A search of PubMed, EMBASE, and the Cochrane database of systematic reviews was performed to identify data compiled through September 2023 for this umbrella review. Randomized controlled trials (RCTs) as the foundation for meta-analyses and peer-reviewed systematic reviews were the primary focus of the literature search. The Grading of Recommendations Assessment, Development, and Evaluation method was used to assess the overall certainty of the evidence, whereas AMSTAR 2 and the Cochrane Collaboration tool were used to evaluate the quality of the included reviews. Following a comprehensive review, three systematic analyses of 27 RCTs were integrated. Acupuncture led to a slightly greater reduction in the recurrence rate of paroxysmal supraventricular tachycardia (SVT) compared to standard pharmaceutical therapy (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.88-1.27; I2 = 56%; P = .55), although the difference was not statistically significant. In contrast, acupuncture significantly outperformed pharmacological treatment in the context of ventricular premature beats (VPBs) (RR, 1.16; 95 CI, 1.08-1.25; I2 = 0%; P < .0001). The reduction in paroxysmal atrial fibrillation (AF)/atrial flutter was increased with acupuncture, albeit without statistical significance (RR, 1.12; 95% CI, 0.88-1.42; I2 = 0%; P = .36). Acupuncture also led to a greater reduction in heart rate (HR) compared to pharmaceutical treatment despite notable heterogeneity and a lack of statistical significance (mean difference, -1.55; 95% CI, -41.37 to 38.28; I2 = 99%; P = .94). Adverse events were effectively managed, affirming the favorable safety profile of acupuncture. Our study suggests that acupuncture leads to a greater reduction in the recurrence rates of VPBs, AF, and atrial flutter but not significantly so in paroxysmal SVT or post-treatment HR. While promising for specific arrhythmias, the varying effectiveness of acupuncture underscores the need for further research and clinical assessment to determine its precise role and suitability in managing particular cardiac conditions.

Maternal Injection with Dexamethasone Results in Female-Biased Autonomic Dysregulation in Rat Offspring

Autonomic dysfunction is an underlying risk factor for cardiovascular disease (CVD). Maternal injection of the synthetic GC dexamethasone (DEX) during the last 4 days of gestation results in female-biased increases in stress-responsive pressor (MAP), heart rate (HR) and altered heart rate variability (HRV) in adult rat offspring, suggesting a role for GC-mediated programming of autonomic function. The present study used pharmacological antagonists for adrenergic (SYM) or cholinergic (PS) receptors to investigate the degree to which changes in SYM or PS activity underlie the autonomic dysfunction in offspring of dams injected with DEX during late gestation. Naïve breeders were injected with DEX (0.4mg/kg/day, s.c.) or vehicle (hydroxypropyl beta cyclodextrin; Veh) on gestation days 18-21. Radiotelemetry was used in adult offspring for recording HR, MAP, and HRV (root mean square of successive differences: RMSSD). At 10-11 weeks rats were randomly assigned to receive SYM antagonists, α-adrenoceptor (prazosin; 0.5mg/kg, i.p.) + β-adrenoceptor (atenolol; 1mg/kg, i.p.), a PS antagonist (homatropine methylbromide; 0.2mg/kg, i.p), or saline (SAL, i.p.). Evaluations were made over 20 min following injection and then during a 20 min restraint. Females were tested on diestrus. In utero DEX exposure resulted in significantly lower RMSSD, an index of vagal tone, in DEX-exposed females and males. PS blockade significantly reduced RMSSD in Veh-, but not DEX-exposed female offspring. SYM blockade did not influence RMSSD in females. In males, PS blockade reduced in RMSSD in both DEX- and Veh-exposed offspring. SYM blockade only reduced RMSSD in males exposed to DEX. Area under the curve (AUC) analysis revealed that in female offspring, SYM blockade resulted in a greater reduction in HR in DEX-exposed offspring, compared to Veh (DEX-SYM: −220 bpm vs. DEX-SAL; Veh-SYM: −197 bpm vs. VEH-SAL) and during restraint (DEX-SYM: −535 bpm vs. DEX-SAL; Veh-SYM: −342 bpm vs. VEH-SAL). PS blockade resulted in a greater increase in HR in Veh-exposed females both following the injection (Veh-PS: −187 bpm vs. VEH-SAL; DEX-PS: −101 bpm vs. DEX-SAL) and during restraint (Veh-PS: −161 bpm vs. VEH-SAL; DEX-PS: −61 bpm vs. DEX-SAL). AUC analysis for MAP showed similar responses to those for HR with SYM blockade having a greater impact in DEX-exposed females and PS blockade having a greater effect in Veh-exposed females. By contrast, in male offspring in utero DEX exposure did not influence HR or MAP responses to SYM or PS blockade. Overall, these findings suggest that maternal DEX injections alter autonomic development primarily in in female offspring and is characterized by a shift from PS to SYM predominance. Better understanding of the mechanisms involved in this programming are important for identifying individuals at risk for CVD and development of interventional strategies for prevention of CVD. Funding: NIH U54 MH118919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Systematic Review and Meta-Analysis of Randomised Controlled Trials Assessing Clinical and Haemodynamic Outcomes of Ivabradine in Heart Failure With Reduced Ejection Fraction Patients

Ivabradine, a pure bradycardic agent, can be given to heart failure reduced ejection fraction (HFrEF) patients with a sinus rhythm of ≥70 bpm on a maximum beta blocker dose, or when beta blockers are contraindicated. This study aimed to see how ivabradine affects the clinical and haemodynamic outcomes of HFrEF patients. This systematic review and meta-analysis searched ClinicalTrials.gov, OpenMD, ProQuest, PubMed, and ScienceDirect for potential articles. All relevant data were extracted. For all pooled effects, the random effect model was applied. A total of 18,972 heart failure (HF) patients from nine randomised clinical trials (RCTs) were involved in this study. Ivabradine decreased the risk of HF mortality (RR 0.79; 95% CI 0.64-0.98; p=0.03) and HF hospitalisation (RR 0.80; 95% CI 0.65-0.97; p=0.03). Ivabradine was related to a greater reduction in heart rate (MD -12.21; 95% CI -15.47 - -8.96; p<0.01) and left ventricular ejection fraction (LVEF) improvement (MD 3.24; 95% CI 2.17-4.31; p <0.01) compared with placebo. Asymptomatic bradycardia (RR 4.25; 95% CI 3.36-5.39; p<0.01) and symptomatic bradycardia (RR 3.99; 95% CI 3.17-5.03; p<0.01) were higher in the ivabradine group. Ivabradine can reduce the risk of HF mortality and HF hospitalisation in HFrEF patients. Ivabradine also effectively reduces resting heart rate and improves LVEF. However, ivabradine is associated with a greater risk of symptomatic and asymptomatic bradycardia.

Ivabradine in patients with heart failure: a systematic literature review

ABSTRACT Background: Heart failure is a chronic disease linked with significant morbidity and mortality, and uncontrolled resting heart rate is a risk factor for adverse outcomes. This systematic literature review aimed to assess the efficacy, safety, and patient-reported outcomes (PROs) of ivabradine in patients with heart failure (HF) with reduced ejection fraction (HFrEF) in randomized controlled trials (RCTs) and observational studies. Methods: We searched electronic databases from their inception to July 2021 to include studies that reported on efficacy, safety, or PROs of ivabradine in patients with HFrEF. Results: Of 1947 records screened, 51 RCTs and 6 observational studies were identified. Ivabradine on top of background therapy demonstrated a significant reduction in composite outcomes including hospitalization for HF or cardiovascular death. In addition, observational studies suggested that ivabradine was associated with a significant reduction in mortality. Across all studies, ivabradine use on top of background therapy was associated with greater reductions in heart rate, improved EF, and improved health-related quality of life (QoL) and comparable risk of total adverse events compared to those treated with background therapy alone. Conclusions: Ivabradine on top of background therapy is beneficial for heart rate, hospitalization risk for HF, mortality, EF, and patients’ QoL. Moreover, these benefits were achieved with no significant increase in the overall risk of total adverse events.

Pharmacokinetics and efficacy of orallyadministered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.

Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Eight university owned research horses with experimentally induced endotoxemia. Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1mg/kg, PO; FLU), and placebo (PO; PLAC) 2hours after administration of LPS. Plasma APAP was analyzed via LC-MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL-1β, IL-6, IL-8, IL-10, and TNF-α were evaluated by an equine-specific multiplex assay. Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6± 0.3hour after administration. At 4 and 6hours after treatment, both APAP (P= <.001, P= .03, respectively) and FLU (P= .0045 and P< .001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6hours (P= .004 and P= .04), and PLAC at 4hours (P= .05) after treatment. The pharmacokinetics of acetaminophen in endotoxemic horses differ from thosereportedbyprevious studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.

Optimal Heart Rate Control Improves Long-Term Prognosis of Decompensated Heart Failure with Reduced Ejection Fraction

Background and Objectives: An elevated heart rate is an independent risk factor for cardiovascular disease; however, the relationship between heart rate control and the long-term outcomes of patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. This study explored the long-term prognostic importance of heart rate control in patients hospitalized with HFrEF. Materials and Methods: We retrieved the records of patients admitted for decompensated heart failure with a left ventricular ejection fraction (LVEF) of ≤40%, from 1 January 2005 to 31 December 2019. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure (HHF) during follow-up. We analyzed the outcomes using Cox proportional hazard ratios calculated using the patients' heart rates, as measured at baseline and approximately 3 months later. The mean follow-up duration was 49.0 ± 38.1 months. Results: We identified 5236 eligible patients, and divided them into five groups on the basis of changes in their heart rates. The mean LVEFs of the groups ranged from 29.1% to 30.6%. After adjustment for all covariates, the results demonstrated that lesser heart rate reductions at the 3-month screening period were associated with long-term cardiovascular death, HHF, and all-cause mortality (p for linear trend = 0.033, 0.042, and 0.003, respectively). The restricted cubic spline model revealed a linear relationship between reduction in heart rate and risk of outcomes (p for nonlinearity > 0.2). Conclusions: Greater reductions in heart rate were associated with a lower risk of long-term cardiovascular death, HHF, and all-cause mortality among patients discharged after hospitalization for decompensated HFrEF.

Heart Rate Recovery Patterns Following Treadmill Test in Normal Individuals

Previous studies evaluating heart rate recovery following treadmill test have significant limitations. We evaluated heart rate recovery pattern in ninety five normal individuals of both genders and different age groups after strictly excluding any cardiac or systemic illness. We observed three distinct patterns of heart rate recovery. Some individuals had significant fall in heart rate during the first minute of recovery. Second group had greater reduction in heart rate during second and third minute of recovery. The third group had nearly similar fall in heart rate during first minute of recovery and during next two minute. However all individuals had a reduction of fifty beats per minute or more during initial three minutes of recovery. Subsequently reduction in heart rate was very slow. None of the individuals reached pre-exercise heart rate up to the end of seven minutes of recovery. Our observations will help better planning of future studies trying to correlate significance of heart rate recovery with diagnosis or prognosis.

Heart Rate Variability and Perceived Stress in Teacher Training: Facing the Reality Shock With Mindfulness?

The beginning of the career of teachers is a demanding phase. In the combined roles of teacher and trainee, and in the shift from academic to practical learning, trainee teachers have to acquire competencies in teaching as well as coping with stress. In this phase, the phenomenon of "reality shock" is widely observed. A mindfulness training was developed to support teacher trainees during their first year. This intervention study investigated perceived and physiological stress at teachers' career start and the stress reducing effects of the mindfulness training in this phase. In a quasi-experimental design, 19 out of 42 participants from this sample underwent mindfulness-based stress reduction training and a wait-list control group (N = 23) underwent a compact course after post measurements. We measured physiological stress parameters and perceived stress at 3 different time points. Heart rate signals were acquired in ambulatory assessment sequences, including teaching, rest periods, and cognitive tasks. The data were analyzed in linear mixed-effects models. We found high physiological stress in the very beginning of teacher training, which attenuated over time. The mindfulness intervention only led to a greater reduction in heart rate (d = .53 to .74) in situations where the intervention group had shown higher heart rate levels initially, but not in heart rate variability. However, the mindfulness group significantly reduced (d = .63) their perceived stress and maintained (d = .55) this improvement, while the control group maintained a highly elevated perceived stress level throughout. The mindfulness training could reduce subjective stress, which otherwise seems to be a long-lasting aspect of beginning teachers' "reality shock". Indications of a superior reduction of physiological stress in demanding situations were weak, while generally, undue physiological stress seems to be a temporary phenomenon in the initial phase of teacher induction.

Screening Design and Response Surface Methodology for the Simultaneous Estimation of Carvedilol and Ivabradine HCl by HPTLC Method.

The combination of carvedilol (CAR) and ivabradine (IVA) is used for a greater reduction in heart rate and for achieving better exercise capacity in a patient with chronic heart failure. Numerous reverse-phase high-pressure liquid chromatography (RP-HPLC) and hyphenated techniques have been reported for the simultaneous estimation of CAR and IVA, but the high-performance thin-layer chromatographic (HPTLC) method has not been reported yet. Hence, the robust HPTLC method has been developed by the implementation of an enhanced analytical quality by design approach based on the principles of analytical failure modes critical effect analysis (AFMCEA) and design of experiments (DoE) as per the upcoming ICH Q14 guideline. The AFMCEA was started by the identification of potential analytical failure modes followed by their critical effect analysis by a DoE-based screening design. The high-risk failure modes were optimized by DoE-based response surface methodology. The method operable design ranges and control strategy was framed for optimized chromatography conditions. The HPTLC method was validated as per ICH Q2 (R1) guideline. The HPTLC method was applied for the assay of FDC of CAR and IVA, and results were found in compliance with the labeled claim. The developed method can be used as an alternative to the published RP-HPLC method for quality control of FDC of CAR and IVA in the pharmaceutical industry.

Hemodynamic response to low-flow acute supplemental oxygen in idiopathic pulmonary fibrosis and elderly healthy subjects

BackgroundHemodynamic response to supplemental oxygen in idiopathic pulmonary fibrosis (IPF) is still not well known. ObjectiveTo determine and compare the effect of low-flow acute supplemental oxygen on the hemodynamics of IPF patients and matched healthy subjects. MethodsDescriptive and comparative study in 20 IPF-patients and 19 Control-subjects, (60-80 years old) breathing ambient air followed by acute nasal low-flow (3 L/min) supplemental oxygen. Non-invasive methods were used during the supine position to evaluate oxygen saturation, heart rate, stroke volume index, cardiac output index, total peripheral resistance and arterial blood pressure. ResultsBreathing ambient air, IPF (vs. Control) presented lower values in stroke volume index (38.7 [29.4–43.2] vs. 45.4 [38.4–50.9] mL•kg-1•m2; p=0.009) and cardiac output index (2.484 [2.268 – 2.946] vs. 2.857 [2.628 – 3.054] L•min−1•m−2; p=0.028), with higher total peripheral resistance (1644 [1559–2076] vs. 1505 [1366–1784] dyne•s•cm−5; p=0.017). During supplemental oxygen (vs. ambient air), both groups increased oxygen saturation above 94% (p<0.001) while heart rate decreased about 6 to 8% (p<0.001); stroke volume index increased around 7% in the Control-group (p=0.004) but only 1% in the IPF-group (p=0.017). In addition, IPF showed increments in total peripheral resistance (1644 [1559–2076] vs. 1706 [1554–2278] dyne•s•cm−5; p=0.017) with subsequent decrements in cardiac output index (2.484 [2.268 – 2.946] vs. 2.362 [2.139 – 2.664] L•min−1•m−2; p<0.001). ConclusionLow-flow acute supplemental oxygen in IPF causes a meaningful decrement in cardiac output due to greater reduction in heart rate and increment in total peripheral resistance than matched healthy subjects. Knowing the hemodynamic profile of IPF patients may be helpful in determining their management with supplemental oxygen.

Systemic NOS inhibition reduces contracting muscle oxygenation more in intact female than male rats

Females respond to baroreceptor stimulation with enhanced modulation of heart rate (HR) to regulate blood pressure and also express greater reliance on nitric oxide (NO) for vascular control compared to males. Sex differences in muscle oxygenation consequent to central hemodynamic challenge induced by systemic NO synthase (NOS) inhibition are unknown. We tested the hypotheses that systemic NOS inhibition would induce lower contracting skeletal muscle oxygenation in females compared to males. The spinotrapezius of Sprague-Dawley rats (females (♀) = 9, males (♂) = 9) was surgically exposed and contracted by electrical stimulation (180s, 1 Hz, ~6 V) under pentobarbital sodium anesthesia. Oxyphor G4 was injected into the muscle and phosphorescence quenching was used to measure the interstitial PO2 (PO2is, determined by O2 delivery-to-utilization matching) under control (Krebs-Henseleit solution) and after intra-arterial infusion of nitro-l-arginine methyl ester (l-NAME; NOS blockade; 10 mg kg−1). At rest, females showed a greater PO2is increase (ΔPO2is/ΔMAP) and HR (ΔHR/ΔMAP) reduction than males in response to the elevated MAP induced by systemic NOS inhibition (both p < 0.05). Following l-NAME, during the contracting steady-state, females exhibited lower PO2is than males (♂: 17.1 ± 1.4 vs ♀: 10.8 ± 1.4 mmHg, p < 0.05). The rate pressure product was lower in females than males (♂: 482 ± 14 vs ♀: 392 ± 29, p < 0.05) and correlated with the steady-state PO2is (r = 0.66, p < 0.05). These results support that females express greater reductions in HR than males in response to l-NAME-induced elevation of MAP via the baroreceptor reflex and provide new insights on how central hemodynamics affect skeletal muscle oxygenation in a sex-specific manner.

Short-term hemodynamic effects of β-blockers influence survival of patients with decompensated cirrhosis

Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1 to 3 months of treatment (short-term). Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under β-blockers, decompensated patients had lower portal pressure decrease (10± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with β-blockers than survivors (21±14% vs. 15 ± 16%; p <0.05) and CO under β-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p= 0.004). In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to β-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis. β-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portalpressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of β-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of β-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.

CYP2D6 polymorphism and its impact on the clinical response to metoprolol: A systematic review and meta-analysis.

CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain. We conducted a systematic review on the effects of CYP2D6 polymorphism on the clinical response to metoprolol. Searches were conducted using MEDLINE. Meta-analyses were performed on the impact of CYP2D6-inferred phenotypes on heart rate (HR) reduction, diastolic (DBP) and systolic (SBP) blood pressure reduction, average daily doses, all-type adverse events and bradycardia. Our qualitative assessment indicated inconsistent results in individual studies and endpoints, but CYP2D6 poor metabolizers (PM) generally presented a greater reduction in HR. The meta-analysis of 15 studies, including a total of 1146 individuals, found a reduction in HR of 3 beats/min (P = .017), and of SBP and DBP by 3 mmHg (P = .0048) for PM compared to non-PM individuals using similar metoprolol doses. Bradycardia appeared more frequent by 4-fold for PM, although significant heterogeneity was observed regarding bradycardia, which limits the scope of this finding. Patients without any CYP2D6 metabolic capacities appear to have increased reduction in DBP, HR and SBP during metoprolol treatment and may be at a higher risk of bradycardia compared to patients with active CYP2D6 phenotypes. Further prospective data are required to determine whether CYP2D6 is associated with clinical events in patients treated with metoprolol, as well as to demonstrate the clinical utility of an individualized approach of prescribing metoprolol using CYP2D6-inferred phenotypes.

PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure: Results of the PRIME-HF Trial

BackgroundIvabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. MethodsPRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated β-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, β-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). ResultsOverall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean −10.0 beats/min, 95% CI −15.7 to −4.3 vs 0.7 beats/min, 95% CI −5.4 to 6.7, P = .011). Patient-reported outcomes, β-blocker use/dose, and safety events were similar (all P > .05). ConclusionsIvabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing β-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.

Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure.

We explore the pharmacogenomics of the beta-blocker bucindolol by discussing relevant beta-1 adrenergic receptor (ADRB1) polymorphisms and recent beta-blocker studies. Through this, we will understand how bucindolol may help patients with atrial fibrillation and heart failure with reduced ejection fraction (AF-HFrEF), which carries poor prognosis. Retrospective study of the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial revealed the interaction between the optimal beta-blocker dose and the ADRB1 Arg389 genotype for HFrEF clinical outcomes. Further, a combinatorial genotype analysis in the Beta-Blocker Evaluation of Survival Trial showed that the Arg389Arg genotype, but not the Gly carrier, was associated with 40% lower mortality risk with bucindolol. Finally, the AF-HFrEF subgroup with the ADRB1 Arg389Arg genotype had greater heart rate reduction and suggestion for mortality benefit. Therapeutic response to beta-blockers varies by beta-blocker mechanism, ADRB1 Arg389 genotype, and clinical setting (AF, HFrEF, AF-HFrEF). The ongoing trial A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure prospectively identifies AF-HFrEF patients with favorable genotype for bucindolol to prevent AF recurrence.

Genomic Imprinting Is Implicated in the Psychology of Music

Why do people sing to babies? Human infants are relatively altricial and need their parents’ attention to survive. Infant-directed song may constitute a signal of that attention. In Prader-Willi syndrome (PWS), a rare disorder of genomic imprinting, genes from chromosome 15q11–q13 that are typically paternally expressed are unexpressed, which results in exaggeration of traits that reduce offspring’s investment demands on the mother. PWS may thus be associated with a distinctive musical phenotype. We report unusual responses to music in people with PWS. Subjects with PWS (N = 39) moved more during music listening, exhibited greater reductions in heart rate in response to music listening, and displayed a specific deficit in pitch-discrimination ability relative to typically developing adults and children (N = 589). Paternally expressed genes from 15q11–q13, which are unexpressed in PWS, may thus increase demands for music and enhance perceptual sensitivity to music. These results implicate genomic imprinting in the psychology of music, informing theories of music’s evolutionary history.

Marine Biota and Psychological Well-Being: A Preliminary Examination of Dose-Response Effects in an Aquarium Setting.

Exposure to natural environments can have calming and stress-reducing effects on humans. Moreover, previous studies suggest that these benefits may be greater in areas with higher species richness. Our study took advantage of a “natural experiment” to examine people’s behavioral, physiological, and psychological reactions to increases in levels of marine biota in a large aquarium exhibit during three stages of restocking: Unstocked, Partially stocked, and Fully stocked. We found that increased biota levels were associated with longer spontaneous viewing of the exhibit, greater reductions in heart rate, greater increases in self-reported mood, and higher interest. We suggest that higher biota levels, even in managed settings, may be associated with important well-being and health benefits, particularly for individuals not able to access the natural analogues of managed environments.

Physiological and perceptual effects of precooling in wheelchair basketball athletes

Objective: To investigate the physiological and perceptual effects of three precooling strategies during pre-exercise rest in athletes with a spinal cord injury (SCI).Design: Randomized, counterbalanced. Participants were precooled, then rested for 60 minutes (22.7 ± 0.2°C, 64.2 ± 2.6%RH).Setting: National Wheelchair Basketball Training Centre, Australia.Participants: Sixteen wheelchair basketball athletes with a SCI.Interventions: Participants were precooled through; 1) 10 minutes of 15.8°C cold water immersion (CWI), 2) ingestion of 6.8 g/kg−1 of slushie (S) from sports drink; 3) ingestion of 6.8 g/kg−1 of slushie with application of iced towels to the legs, torso and back/arms (ST); or 4) ingestion of 6.8 g/kg−1 of room temperature (22.3°C) sports drink (CON).Outcome measures: Core temperature (Tgi), skin temperature (Tsk), heart rate (HR), and thermal and gastrointestinal comfort.Results: Following CWI, a significant reduction in Tgi was observed compared to CON, with a greatest reduction of 1.58°C occurring 40 minutes post-cooling (95% CI [1.07, 2.10]). A significant reduction in Tgi following ST compared to CON was also observed at 20 minutes (0.56°C; [0.03, 1.09]) and 30 minutes (0.56°C; [0.04, 1.09]) post-cooling. Additionally, a significant interaction between impairment level and time was observed for Tgi and HR, demonstrating athletes with a higher level of impairment experienced a greater reduction in HR and significant decrease in rate of decline in Tgi, compared to lesser impaired athletes.Conclusion: CWI and ST can effectively lower body temperature in athletes with a SCI, and may assist in tolerating warm conditions.

Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients: LIFE Study.

In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular mass×wall stress×heart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P≤0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P≤0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.

The Effect of Park and Urban Environments on Coronary Artery Disease Patients: A Randomized Trial.

Aim. To test the hypothesis that walking in a park has a greater positive effect on coronary artery disease (CAD) patients' hemodynamic parameters than walking in an urban environment. Methods. Twenty stable CAD patients were randomized into two groups: 30-minute walk on 7 consecutive days in either a city park or busy urban street. Wilcoxon signed-rank test was employed to study short-term (30 min) and cumulative changes (following 7 consecutive days of exposure) in resting hemodynamic parameters in different environments. Results. There were no statistically significant differences in the baseline and peak exercise systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), exercise duration, or HR recovery in urban versus park exposure groups. Seven days of walking slightly improved all hemodynamic parameters in both groups. Compared to baseline, the city park group exhibited statistically significantly greater reductions in HR and DBP and increases in exercise duration and HR recovery. The SBP and DBP changes in the urban exposed group were lower than in the park exposed group. Conclusions. Walking in a park had a greater positive effect on CAD patients' cardiac function than walking in an urban environment, suggesting that rehabilitation through walking in green environments after coronary events should be encouraged.