Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

The effect of naratriptan on cardiac autonomic function in patients with migraine: a placebo controlled pilot study

Aim. Naratriptan is a new member of the triptans which are used in aborting attacks of migraine. But triptans may cause chest pain, myocardial infarction and arrhythmias in some patients. Naratriptan shows antimigraine effect by activating 5HT(1B/1D) receptors. The activation of 5HT(1B/1D) receptors also reduces the secretion of noradrenaline from cardiac sympathetic nerves. The effect of naratriptan on cardiac autonomic function is not known. The aim of this study is to find out, if any the effect of naratriptan on cardiac autonomic function by evaluating time and frequency domain parameters of heart rate variability. Methods. Nine patients with migraine (8 women, mean age: 37+/-4 years) were included in a pilot, double blinded, crossover and randomized study. All participants took 2.5 mg naratriptan or placebo at least 5 days apart. Both time domain and frequency domain heart rate variability (HRV) parameters were obtained during rest, controlled respiration and handgrip exercise, before and 2 hours later naratriptan or placebo administration. Results. Baseline HRV parameters were similar before administration of naratriptan or placebo. Time domain parameters [and mean RR interval, the standard deviation of R-R interval (SDNN) and the root mean square of successive R-R interval differences (RMSSD)] and frequency domain parameters [low frequency (LF) and high frequency (HF) spectral powers and LF/HF ratio] obtained after naratriptan administration were not different when compared with placebo. Conclusions. A single dose 2.5 mg oral naratriptan administration did not change sympathetic, parasympathetic reactivity and sympathovagal balance in migraneurs

A heart rate turbulence study to assess cardiac autonomic function in migraineurs

Studies of autonomic nervous system function in patients with migraine have shown conflicting results. Heart rate turbulence (HRT) is a new method to assess cardiac autonomic function. HRT impairment reflects cardiac autonomic dysfunction. The aim of the present study was to determine validation of HRT as an autonomic function test in patients with migraine in comparison with the normal population. Forty-four patients with migraine and fifty healthy subjects were included to the study. Twenty-four hours ambulatory electrocardiograms were recorded. HRT parameters, turbulence onset (TO) and turbulence slope (TS) were calculated. in 16 migraineurs and 22 control subjects we were not able to calculate HRT because HRT calculation is impossible in subjects who do not have any ventricular premature beat (VPB) in their Holter recordings. These subjects were excluded from statistical analyses. HRT were calculated in 28 migraineurs (mean age 47.4 ± 10.1 years, 20 women) and 28 control subjects (mean age 47.5 ± 11.6 years, 20 women). There were no significant differences in two HRT parameters; TO and TS between migraineurs and control subjects (TO migraineur: -0.65 ± 3.84%, TO control: -0.61 ± 4.42%, p = 0.38; TS migraineur: 9.34 ± 7.50 ms/RR, TS control: 8.82 ± 6.34 ms/ RR, p = 0.40, respectively). HRT parameters, which determine the cardiac autonomic dysfunction, did not seem to be altered in patients with migraine

The effect of dopamine type-2 receptor blockade on autonomic modulation

Dopamine2 (D2)-like receptor antagonists are widely used for the treatment of gastroparesis and vomiting. Metoclopramide (MCP), a peripheral and central D2-like receptor antagonist, stimulates the sympathetic nervous system and may alter autonomic modulation, but the net effect of MCP to the heart is not known. The aim of our study was to investigate the effects of MCP on cardiac autonomic modulation, using power spectral analysis of heart rate variability

ONE-YEAR PREVALENCE OF MAJOR DEPRESSIVE DISORDER AND RELATED SOCIOECONOMIC FACTORS IN IZMIR CITY CENTER

WOS: 00034728070061

What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?

PubMedID: 30270069Background and aims: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of large-scale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2). Methods: A-HIT1 is a survey of homozygous FH patients undergoing low density lipoprotein (LDL) apheresis (LA). A-HIT2 is a registry of adult FH patients (homozygous and heterozygous) admitted to outpatient clinics. Both registries used clinical diagnosis of FH. Results: A-HIT1 evaluated 88 patients (27 ± 11 years, 41 women) in 19 centers. All patients were receiving regular LA. There was a 7.37 ± 7.1-year delay between diagnosis and initiation of LA. LDL-cholesterol levels reached the target only in 5 cases. Mean frequency of apheresis sessions was 19 ± 13 days. None of the centers had a standardized approach for LA. Mean frequency of apheresis sessions was every 19 ± 13 (7–90) days. Only 2 centers were aware of the target LDL levels. A–HIT2 enrolled 1071 FH patients (53 ± 8 years, 606 women) from 31 outpatients clinics specialized in cardiology (27), internal medicine (1), and endocrinology (3); 96.4% were heterozygous. 459 patients were on statin treatment. LDL targets were attained in 23 patients (2.1% of the whole population, 5% receiving statin) on treatment. However, 66% of statin-receiving patients were on intense doses of statins. Awareness of FH was 9.5% in the whole patient population. Conclusions: The first nationwide FH registries revealed that FH is still undertreated even in specialized centers in Turkey. Additional effective treatment regiments are urgently needed. © 2018 Elsevier B.V.Sanofi Pfizer AmgenA-HIT1 and 2 registries are sponsored by the Turkish Society of Cardiology that receives funding from a variety of sources (including unrestricted research grants from Aegerion, Amyrit, Amgen, Pfizer, and Sanofi). Appendix