Implications of pulse wave velocity and central pulse pressure in heart failure with reduced ejection fraction.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) and central pulse pressure (PP) are recognised as significant indicators of vascular health and predictors of cardiovascular outcomes. In this study, associations between central hemodynamics and left ventricular (LV) echocardiographic parameters were investigated in subjects with heart failure with reduced ejection fraction (HFrEF), comparing the results to healthy individuals. METHODS AND RESULTS: This cross-sectional prospective controlled study included 50 subjects with HFrEF [mean LV ejection fraction (EF) 26 ± 6.5%] and 30 healthy controls (mean LVEF 65.9 ± 5.3%). Pulse wave analysis (PWA) and carotid-femoral pulse wave velocity (cfPWV) were used to measure central hemodynamics and arterial stiffness. The HFrEF group displayed higher cfPWV (8.2 vs. 7.2 m/s, p = 0.007) and lower central (111.3 vs. 121.7 mmHg, p = 0.001) and peripheral (120.1 vs. 131.5 mmHg, p = 0.002) systolic blood pressure. Central pulse pressure (PP) was comparable between the two groups (37.6 vs. 40.4 mmHg, p = 0.169). In the HFrEF group, cfPWV significantly correlated with left ventricular end-diastolic volume (LVEDV) index (mL/m2) and LVEF, with LVEDV index being a significant independent predictor of cfPWV (R2 = 0.42, p = 0.003). Central PP was significantly associated with heart rate, LVEF and LVEDV index, with the latter being a significant independent predictor of central PP (R2 = 0.41, p < 0.001). These correlations were not observed in healthy controls. CONCLUSIONS: Significant associations between central hemodynamic measures and LV echocardiographic parameters were identified, suggesting the potential to use PWA and cfPWV as possible tools for managing HFrEF.

What is the context?Heart failure with reduced ejection fraction (HFrEF) affects millions of people worldwide.Vascular health plays a significant role in the development and progression of HFrEF.This study investigates two indicators of arterial stiffness­pulse wave velocity (PWV) and central pulse pressure (PP)­and their impact on the functioning of the heart in HFrEF patients compared to healthy individuals.What is new?The study found that higher carotid-femoral PWV and central PP, which typically indicate worse vascular health, were associated with better heart function in HFrEF patients. This paradoxical finding suggests that in the context of HFrEF, traditional markers of vascular health may have different implications.The study included non-invasive methods to evaluate these indicators, offering a potential new additional approach for monitoring and managing HFrEF.What is the impact?We could possibly use non-invasively evaluated PWV and central PP (measures of vascular function) as markers of left ventricular function assessment in HFrEF.

Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 trial.

AIMS: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. METHODS AND RESULTS: In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend < 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction > 0.10 for each). CONCLUSION: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.

Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.

OBJECTIVES: We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. BACKGROUND: Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding. METHODS: Landmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial. RESULTS: Significant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial. CONCLUSIONS: Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).

No evidence of automatic atrial overdrive pacing efficacy on reduction of paroxysmal atrial fibrillation.

AIMS: Paroxysmal atrial fibrillation (PAF) is frequently encountered in pacemaker patients, most commonly in sick sinus syndrome. The combination of site-specific pacing in conjunction with an overdrive algorithm combined with antiarrhythmic drugs on the incidence of PAF in patients with a conventional indication for pacing is unknown. METHODS AND RESULTS: Patients with pacemaker indication and PAF received a DDDR-pacemaker, which included an automatic atrial overdrive (AO) algorithm. The atrial lead was implanted in either the right atrial appendage (RAA) (n = 83) or the right low-atrial septum (LAS) (n = 94). The algorithm was switched on or off in a 3 month, single blind crossover design and antiarrhythmic drugs were kept stable. A control group of 96 patients (LAS, n = 14; RAA, n = 84) without PAF served as controls to assess any proarrhythmic effect of overdrive pacing. Atrial fibrillation (AF) burden defined as cumulative time in mode switch was not reduced during automatic AO from either the RAA or from the LAS. The reduction was not effective both for AF of short (<24 h) and long (> or =24 h) duration. There was no atrial proarrhythmia induced by the overdrive algorithm in the control group. CONCLUSIONS: We could not demonstrate a reduction of AF burden defined as cumulative time in AF by the AO algorithm, in patients who are paced for standard indications and PAF, neither from the RAA nor from the LAS.

Diagnosis and treatment of acute myocardial infarction in tertiary and secondary care hospitals in Estonia.

AIM: To compare validity of AMI diagnosis and treatment of AMI patients between tertiary and secondary care hospitals in Estonia. METHODS: Two tertiary and seven secondary care hospitals responsible for the treatment of most AMI patients in Estonia were included in the analysis. A random sample of 520 patients admitted to these hospitals with AMI in 2001 was taken from the Estonian Health Insurance Fund database. Medical records were reviewed by trained experts using a standardized data collection form. RESULTS: Forty cases were excluded due to selection errors by the Health Insurance Fund. Of the remaining cases, a diagnosis of AMI was confirmed in 93.3% of cases in tertiary care hospitals and in 83.5% of cases in secondary care hospitals (p < 0.001). A total of 210 cases from tertiary and 213 cases from secondary care hospitals with confirmed AMI diagnoses were included in subsequent analysis. Utilization of beta-blockers, aspirin, and reperfusion therapy was similar in both types of hospitals. In tertiary care hospitals, ACE inhibitors and statins were more frequently used during hospital stay and recommended at discharge compared with secondary care hospitals. In-hospital mortality was similar in both types of hospitals both before and after adjustment. CONCLUSIONS: Tertiary care physicians adhered more strictly to the current definition and guidelines for the management of AMI than did secondary care physicians. However, there is still a need for further improvement in both hospital settings according to international guidelines.