Heart rate and heart failure.

PURPOSE OF REVIEW: Resting heart rate has long been thought to be a risk factor in cardiovascular disease and a prognostic factor in heart failure. ß-Blockers were originally used in heart failure for their heart rate control abilities. However, they also have negative inotropic effects contributing to their overall benefit. The role of isolated heart rate modification is unclear in left ventricular systolic dysfunction. RECENT FINDINGS: Two recent studies looked at the heart rate-lowering effects of the If, or funny current inhibitor ivabradine and its potential role in heart failure therapy. At the doses chosen for the studies, ivabradine is presumed to have only effects on heart rate with no other cardiotropic effects. Thus, the cardiovascular outcome benefits are presumed to be secondary to heart rate modification. SUMMARY: The two recent trials showed both heart rate and cardiovascular events to be significantly lower in the ivabradine-treated group of patients with left ventricular systolic dysfunction and initial heart rate at least 70 beats/min. However, neither of these trials proved causality. Hence, the link between heart rate and improved cardiovascular outcomes still remains muddled.

Heart failure and sleep-disordered breathing.

PURPOSE OF REVIEW: Sleep-disordered breathing, which includes both obstructive and central sleep apnoea (OSA and CSA, respectively), is highly prevalent in patients with heart failure. In this review, we outline our current understanding of the bidirectional relationship between these disorders and heart failure. We also explore the role of recent advances in therapeutics. RECENT FINDINGS: Although early studies suggest promise of adaptive servoventilation in treating sleep-disordered breathing, particularly CSA with associated Cheyne-Stokes respiration, the recent clinical trial in the heart failure patient population has demonstrated worse cardiovascular outcome in symptomatic patients. SUMMARY: Both OSA and CSA are highly prevalent in patients with heart failure. Effective treatment of OSA with continuous positive airway pressure can improve cardiovascular outcome in these patients. However, recent evidence suggests that adaptive servoventilation cannot be safely recommended as a therapy for CSA in the context of heart failure, as a result of increased risk of cardiovascular mortality.

Antithrombotic therapies in Canadian atrial fibrillation patients with concomitant coronary artery disease: Insights from the CONNECT AF + PCI-II program.

BACKGROUND: Selecting the appropriate antithrombotic regimen for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) or have had medically managed acute coronary syndrome (ACS) remains complex. This multi-centre observational study evaluated patterns of antithrombotic therapies utilized among Canadian patients with AF post-PCI or ACS. METHODS AND RESULTS: By retrospective chart audit, 611 non-valvular AF patients [median (interquartile range) age 76 (69-83) years, CHADS2 score 2 (1-3)] who underwent PCI or had medically managed ACS between August 2018 and December 2020 were identified by 68 cardiologists across eight provinces in Canada. Overall, triple antithrombotic therapy [TAT: combined oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT)] was the most common initial antithrombotic strategy, with use in 53.8 % of patients, followed by dual pathway therapy (32.7 % received OAC and a P2Y12 inhibitor, and 4.1 % received OAC and aspirin) and DAPT (9.3 %). Median duration of TAT was 30 (7, 30) days. Compared to the previous CONNECT AF + PCI-I program, there was an increased use of dual pathway therapy relative to TAT over time (P-value <.0001). DOACs (direct oral anticoagulants) represented 90.3 % of all OACs used overall, with apixaban being the most utilized (50.5 %). Proton pump inhibitors were used in 57.0 % of all patients, and 70.1 % of patients on ASA. Planned antithrombotic therapies at 1 year were: 76.2 % OAC monotherapy, 8.3 % OAC + ASA, 7.9 % OAC + P2Y12 inhibitor, 4.3 % DAPT, 1.3 % ASA alone, and <1 % triple therapy. CONCLUSION: In accordance with recent Canadian Cardiovascular Society guideline recommendations, we observed an increased use of dual pathway therapy relative to TAT over time in both AF patients post-PCI (elective and emergent) and in those with medically managed ACS. Additionally, DOACs have become the prevailing form of anticoagulation across all antithrombotic regimens. Our findings suggest that Canadian physicians are integrating evidence-based approaches to optimally manage the bleeding and thrombotic risks of AF patients post-PCI and/or ACS.

CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction.

In this update of the Canadian Cardiovascular Society heart failure (HF) guidelines, we provide comprehensive recommendations and practical tips for the pharmacologic management of patients with HF with reduced ejection fraction (HFrEF). Since the 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of HF, substantial new evidence has emerged that has informed the care of these patients. In particular, we focus on the role of novel pharmacologic therapies for HFrEF including angiotensin receptor-neprilysin inhibitors, sinus node inhibitors, sodium glucose transport 2 inhibitors, and soluble guanylate cyclase stimulators in conjunction with other long established HFrEF therapies. Updated recommendations are also provided in the context of the clinical setting for which each of these agents might be prescribed; the potential value of each therapy is reviewed, where relevant, for chronic HF, new onset HF, and for HF hospitalization. We define a new standard of pharmacologic care for HFrEF that incorporates 4 key therapeutic drug classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (as first-line therapy or after angiotensin converting enzyme inhibitor/angiotensin receptor blocker titration); a ß-blocker; a mineralocorticoid receptor antagonist; and a sodium glucose transport 2 inhibitor. Additionally, many patients with HFrEF will have clinical characteristics for which we recommended other key therapies to improve HF outcomes, including sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in combination, and/or digoxin. Finally, an approach to management that integrates prioritized pharmacologic with nonpharmacologic and invasive therapies after a diagnosis of HFrEF is highlighted.

A novel method to link and validate routinely collected emergency department clinical data to measure quality of care.

The objective was to develop and validate a method to link routinely captured electronic data for the measurement of emergency department (ED) quality indicators. Electronic ED data were linked to calculate time to antibiotics and time to electrocardiogram (ECG) for pneumonia and chest pain patients, respectively; validation was by comparison with chart data. Linked electronic data correctly identified 40/40 pneumonia and 65/65 chest pain patients. The median difference in time to antibiotics calculated from linked electronic data versus chart data was 6 minutes (standard deviation [SD] = 14.0); for time to ECG it was 0 minutes (SD = 70). The percentage of ED patients meeting target time to antibiotics was 47% with electronic data versus 44% with charts; for time to ECG, 8% met target time with electronic data versus 11% with charts. A simple computer algorithm for linking routine ED electronic data for quality-of-care measurement was validated.

Gas-phase ambient air contaminants exhibit significant dioxin-like and estrogen-like activity in vitro.

Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR)-based and estrogen receptor (ER)-based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum (Sigma) of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10-100 times more abundant than that of Sigmapolychlorinated biphenyls, Sigmanitro-polycyclic aromatic hydrocarbons, and Sigmaorganochlorine pesticides, and 10(3) to 10(4) times more abundant than Sigmapolychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways.

Intravenous morphine and topical tetracaine for treatment of pain in [corrected] neonates undergoing central line placement.

CONTEXT: There is limited evidence of the analgesic effectiveness of opioid analgesia or topical anesthesia during central line placement in neonates, and there are no previous studies of their relative effectiveness. OBJECTIVE: To determine the effectiveness and safety of topical tetracaine, intravenous morphine, or tetracaine plus morphine for alleviating pain in ventilated neonates during central line placement. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, controlled trial enrolling 132 ventilated neonates (mean gestational age, 30.6 [SD, 4.6] weeks at study entry) and conducted between October 2000 and July 2005 in 2 neonatal intensive care units in Toronto, Ontario. INTERVENTIONS: Prior to central line insertion, neonates were randomly assigned to receive tetracaine (n = 42), morphine (n = 38), or both (n = 31); a separate nonrandomized group of 21 neonates receiving neither tetracaine nor morphine was used as a control group. MAIN OUTCOME MEASURES: The primary outcome measure was a pain score for the proportion of time neonates displayed facial grimacing (brow bulge) during different phases of the procedure (skin preparation, needle puncture, and recovery). In randomized neonates, safety assessments included blood pressure, ventilatory support, and local skin reactions. RESULTS: Compared with no treatment, pain scores were lower in the morphine and tetracaine-morphine groups during skin preparation (mean difference, -0.22; 95% confidence interval [CI], -0.4 to -0.04; P = .02 and -0.29; 95% CI, -0.49 to -0.09; P = .01, respectively), and needle puncture (mean difference, -0.35; 95% CI, -0.57 to -0.13; P = .003 and -0.47; 95% CI, -0.71 to -0.24; P<.001, respectively), but pain scores did not differ statistically for tetracaine alone vs no treatment. Pain scores were lower for morphine and tetracaine-morphine vs tetracaine during the skin preparation phase and for tetracaine-morphine vs tetracaine during needle puncture. Compared with neonates without morphine, morphine-treated neonates required larger increases in ventilation rate in the first 12 hours (mean difference, 3.9/min; 95% CI, 1.3-6.5/min; P = .003). Local skin reactions occurred in 30% of neonates given tetracaine vs 0% for morphine (risk difference, 0.30; 95% CI, 0.19-0.41; P<.001). CONCLUSION: In this study of ventilated neonates undergoing central line placement, morphine and tetracaine plus morphine provided superior analgesia to tetracaine; however, morphine caused respiratory depression and tetracaine caused erythema.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00213200.

Spontaneous coronary artery dissection-A review.

Spontaneous coronary artery dissection (SCAD) is an infrequent and often missed diagnosis among patients presenting with acute coronary syndrome (ACS). Unfortunately, SCAD can result in significant morbidities such as myocardial ischemia and infarction, ventricular arrhythmias and sudden cardiac death. Lack of angiographic recognition from clinicians is a major factor of under-diagnosis. With the advent of new imaging modalities, particularly with intracoronary imaging, there has been improved diagnosis of SCAD. The aim of this paper is to review the epidemiology, etiology, presentation, diagnosis and management of SCAD.

Influence of publicly available online wait time data on emergency department choice in patients with noncritical complaints.

OBJECTIVES: Increased emergency department (ED) wait times lead to more patients who leave without being seen and decreased patient satisfaction. Many EDs post estimated wait times either online or in the ED to guide patient expectations. The objectives of this study were to assess patients' awareness of online wait time data and to investigate patients' willingness to use this information when choosing between two academic EDs in London, Ontario. METHODS: A prospective study was conducted over a 2-month period in a tertiary ED with online available wait times. Patients over 18 years of age assigned a Canadian Triage and Acuity Scale (CTAS) score of 3, 4, or 5 were approached by trained research assistants to complete a 15-item paper-based questionnaire. Multivariable logistic regression models were used to determine factors independently associated with the outcomes. RESULTS: A total of 1,211 patients completed the survey. Of these, 109 (9%) were aware that ED wait time information was available on the Internet; 544 (45%) reported that they would use the available data to make a decision on which ED to visit, and 536 (44%) indicated that they were more likely to go to the ED with a shorter wait time. Age, gender, household income, education, and Internet access were not associated with awareness of online ED wait times. Participants less than 40 years of age were more likely to use online wait time information. CONCLUSION: There is low awareness of the availability of ED wait time data published online in the study locaton. Future research may include the delivery of a public awareness strategy for ED wait time data and a re-evaluation of ED use and patient satisfaction following this.

Lipid modification in the elderly using the combination of a statin and a cholesterol absorption inhibitor.

While the optimal lipid-lowering treatment to reduce cardiovascular disease (CVD) risk in elderly patients has not been definitively established, evidence so far indicates that reducing low-density lipoprotein cholesterol (LDL-C) should be a primary goal, as with other patient groups. The VYTELD (VYTorin in the ELDerly) study--a multicenter, 12-week, randomized, double-blind trial--evaluated the efficacy and safety of combination therapy comprised of ezetimibe plus simvastatin (eze/simva) versus atorvastatin in 1289 hypercholesterolemic patients aged ? 65 years. For all prespecified comparisons, patients randomized to eze/simva were found to have significantly greater percentage decreases in LDL-C and were significantly more likely to achieve LDL-C target levels compared with those on atorvastatin monotherapy (p < 0.05 to < 0.001). Also, the proportions of subjects reaching secondary biochemical targets were similarly greater with eze/simva than with atorvastatin monotherapy for all prespecified comparisons (p < 0.01 to < 0.001). Finally, there were no differences in tolerability between the treatments. The authors concluded that in patients aged ≥ 65 years, the eze/simva combination provided significantly greater improvements in key lipid variables, with a larger proportion of subjects reaching target LDL-C compared with atorvastatin monotherapy. Despite these promising short-term results, the longer-term safety and efficacy of combination treatment across diverse populations requires further evaluation.