Heart failure as a prothrombotic state

Systolic heart failure is a common syndrome and the incidence is expected to increase. Arterial and venous thromboembolic events are common and contribute to mortality. In these patients, a prothrombotic state is present due to flow abnormalities, endothelial dysfunction, an activated sympathetic nervous system and RAAS, and increased systemic inflammation. Current treatment, including beta-blockers and ACEinhibitors, only modestly influences this prothrombotic state. Although anticoagulant therapy may have an important effect in patients with systolic HF is unclear, the beneficial effect has not clearly been established. However, nonselective beta-blockers may be effective in decreasing the prothrombotic state in HF patients.Graph presented. Table presented

Search for HRV-parameters that detect a sympathetic shift in heart failure patients on ß-blocker treatment

Background: A sympathetic shift in heart rate variability (HRV) from high, beat-to-beat, to lower frequencies may be an early signal of deterioration in a monitored patient. Most chronic heart failure (CHF) patients receive ß-blockers. This tends to obscure HRV observation by increasing the fast variations. We tested which HRV parameters would still detect the change into a sympathetic state.Methods and results: ß-blocker (Carvedilol®) treated CHF patients underwent a protocol of 10 minutes supine rest, followed by 10 minutes active standing. CHF patients (NYHA Class II-IV) n=15, 10m/5f, mean age 58.4 years (47-72); healthy controls n=29, 18m/11f, mean age 62.9 years (49-78). Interbeat intervals (IBI) were extracted from the finger blood pressure wave (Nexfin®). Both linear and nonlinear HRV analyses were applied that (1) might be able to differentiate patients from healthy controls under resting conditions and (2) detect the change into a sympathetic state in the present short recordings. Linear: mean-IBI, SD-IBI, rMSSD (root mean square of successive differences), pIBI-50 (the proportion of intervals that differs by more than 50 ms from the previous), LF, HF and LF/HF ratio. Nonlinear: SampEn (sample entropy), MSE (Multiscale entropy) and derived: MSV (Multiscale variance) and MSD (Multiscale rMSSD).In the supine resting situation patients differed from controls by having higher HF and, consequently, lower LF/HF. In addition their longer range (τ=6-10) MSE was lower as well. The sympathetic shift was, in controls, detected by mean-IBI, rMSSD, pIBI-50 and LF/HF, all going down; in CHF by mean-IBI, rMSSD, pIBI-50 and MSD (τ=6-10) going down. MSD6-10 introduced here works as a band-pass filter favoring frequencies from 0.02-0.1Conclusions: In ß-blocker treated CHF patients, traditional time domain analysis (mean-IBI, rMSSD, pIBI-50) and MSD6-10 provide the most useful information to detect a condition change

Systolic heart failure: A prothrombotic state

Systolic heart failure is a common syndrome whose incidence is expected to increase. Several treatment modalities, such as -blockers and angiotensin-converting enzyme inhibitors, improve survival. Whether antithrombotic treatment is effective remains to be elucidated, although observations suggest a prothrombotic state in heart failure. This article focuses on this prothrombotic state and discusses the risk of thromboembolic events, pathophysiological mechanisms, and the potential role of anticoagulant treatment. Copyright © 2009 by Thieme Medical Publishers, Inc

Non-selective vs. selective beta-blocker treatment and the risk of thrombo-embolic events in patients with heart failure

Aims Heart failure (HF) is associated with a prothrombotic state, resulting in an increased risk for thrombo-embolic events. Studies suggest a reduced prothrombotic state when non-selective beta-blockers relative to selective beta-blockers are given. We studied the influence of non-selective beta-blockers compared with selective beta-blockers on the occurrence of arterial and venous thrombo-embolic events in patients with HF. Methods and results Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. In the period of 1998-2007, 20 870 patients were hospitalized for HF. We used Cox regression analysis with time-varying beta-blocker covariate to assess the difference in the incidence of thrombo-embolic events [acute coronary syndrome (ACS), stroke, or pulmonary embolism] among patients. Median follow-up was 2.0 years (inter-quartile range: 0.7-4.1). Directly after discharge, 6558 patients were prescribed a selective beta-blocker and 2202 patients a non-selective beta-blocker. The hazard ratio (HR) for any thrombo-embolic event for non-selective beta-blockers compared with selective beta-blockers was 0.76 [95% confidence interval (CI): 0.64-0.89]. After adjustment, the difference remained (HR 0.84, 95% CI: 0.72-0.99). The effect was most prominent for ACS (HR 0.78, 95% CI: 0.65-0.93), and not clear for stroke (HR 1.00, 95% CI: 0.67-1.50) or pulmonary embolism (HR 1.33, 95% CI: 0.66-2.71). Conclusion In patients with HF, the use of non-selective beta-blockers was associated with a lower risk of thrombo-embolic events than selective beta-blockers. Whether this beneficial effect is caused by the additional beta2-receptor blockade remains to be elucidated. These findings need to be validated in a well-designed randomized stud

Non-selective beta-blockers decrease thrombotic events in patients with heart failure

Background: Beta-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of beta-blockers. The 2002 COMET study showed superiority of carvedilol (a non-selective beta-blocker) over metoprolol (selective beta-blocker) on mortality and cardiovascular events in patients with HF. However, this study was criticised for several reasons. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective beta-blockers. We therefore hypothesised that non-selective beta-blockers reduce vascular events compared to selective beta-blockers in patients with HF. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. We identified a cohort of 20,870 patients with documented HF in the period 1998 to 2007, based on hospital discharge diagnosis. This method has been validated for selecting HF patients. We used Cox regression analysis, with time varying beta-blocker covariate to assess the difference in the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and non-selective beta-blockers. Results: Median follow-up was 2.0 years (interquartile range (IQR): 0.7-4.1). Directly after discharge, 6,980 patients were prescribed a selective beta-blocker and 2,504 patients a non-selective beta-blocker. Total follow-up was 56,667 person-years, of which 18,245 person-years for selective beta-blockers and 6,455 for non-selective beta-blockers. The hazard ratio (HR) for any thrombotic event for non-selective beta-blockers compared to selective beta-blockers was 0.76 (95% confidence interval (CI): 0.64-0.89). After adjustment for potential confounders the difference remained significant (HR 0.84, 95%CI: 0.72-0.99). Conclusion: Non-selective beta-blockers are associated with a lower risk of thromboembolic events compared to selective beta-blockers in patients with HF. The hypothesis that non-selective beta-blockers reduce the prothrombotic state in these patients should be further explored

Time-trends in treatment and cardiovascular events in patients with heart failure: a pharmacosurveillance study

Aims We assessed, in patients with a first hospitalization for heart failure (HF), the temporal relationship of the incidence of cardiovascular events, all-cause mortality, and cardiovascular drug treatment. Methods and results Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. Patients were selected based on a first hospital discharge diagnosis of documented HF. Two time-periods were compared: 1998-2002 and 2003-07. In each time-period, we analysed all prescribed cardiovascular medications, all-cause mortality, and cardiovascular events (rehospitalization for HF and ischaemic events) within the first year after hospitalization, and the occurrence of ischaemic events separately (myocardial infarction and ischaemic stroke). Cox-regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). We identified 8276 patients in 1998-2002 and 9548 patients from 2003-07. There was an increase in almost all cardiovascular medication prescriptions in the second period: in particular, beta-blocker prescriptions rose from 36% in 1998-2002 to 55% in 2003-07. In the first year after hospitalization, there was no difference in all-cause mortality or any cardiovascular event (HR 1.00, 95% CI: 0.95-1.05), as a composite endpoint or when analysed separately. The incidence of ischaemic events decreased from 2.7 to 1.9% in the first and second time-period, respectively (HR 0.74, 95% CI: 0.61-0.90). Conclusion Prescription of cardiovascular medications in patients with a first hospitalization for HF has increased in recent years, particularly for beta-blockers, and the incidence of ischaemic events may have decreased. There was no decrease in all-cause mortality or cardiovascular event

Time trends in cardiovascular drug treatment and cardiovascular events in patients with acute heart failure

Background: Heart failure (HF) is associated with an increased risk of thrombotic events, which can be reduced by adequate drug treatment. We assessed the temporal relationship of the incidence of myocardial infarction (MI) and stroke, and the specific cardiovascular treatment that was given. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. Patients were selected based on a first hospital discharge diagnosis of documented HF. Two time intervals were compared: 1998-2002 and 2003-2007. We analyzed prescribed medication in the first 90 days after hospitalization, and the occurrence of MI and strokes in the first year after hospitalization. Logistic-regression analysis was performed to calculate odds ratios (OR) between the two periods. Results: We identified 6526 patients in 1998-2002 and 6369 patients from 2003-2007. During the first year after acute HF, the incidence of thrombotic events was 4.1% and 3.4% in the two periods, respectively. After adjustment for age and previous thrombotic events the incidence was 21% lower in 2003-2007 (Table). Prescription of ACE-inhibitors and beta-blockers has increased in the recent years, but were still prescribed to only 60% of HF patients (Table). Conclusion: The incidence of thrombotic events appears to have decreased in patients with acute HF, which may be due to better use of medication. However, many patients remain undertreated (Table persent)