Beta-blocker Usage Research Articles

PCV91 BETA BLOCKERS AND DIURETICS USAGE IN CROATIA AND SLOVENIA DURING A NINE-YEAR PERIOD

Objective: Cardiovascular diseases are the major health problem and adequate therapy, which includes usage of beta blockers (ATC, C07) and diuretics (ATC, C03), leads to reduction of cardiovascular morbidity and mortality. The aim of our study was to identify and analyze changes in the usage of these drugs in Croatia and Slovenia from 2000-2008 and to identify the rate of the generic drugs usage as well as the average price for 1 DDD. Methods: The data concerning consumption have been obtained from the International Medical Statistics database for Croatia and they are presented in defined daily doses per 1000 inhabitants per day (DDD/1000). Financial expenditure data are presented in Euros and the average cost per DDD was calculated for each drug group. Results: The total usage of diuretics is on average 19% higher in Croatia and continually increasing in both countries. Consumption rate of furosemid among diuretics is lower in Slovenia (43.96% in 2008), while in Croatia 67.28% (2008). The generic drugs usage is higher in Croatia during the whole investigated period, e.g. in 2008, 87.4 % of all prescribed diuretics were generics in Croatia, and in Slovenia 59.4%. The average price per 1 DDD was more than twice lower in Croatia (0.08 EUR/DDD vs. 0.17 EUR/DDD in Slovenia). The beta blockers drugs usage is 13% higher in Slovenia, but generic drugs usage is higher in Croatia. Conclusions: Increased diuretics and beta blockers drug usage is comparable to worldwide trends, but drug prescribing patterns are different when comparing both countries. Although the generic drugs usage is relatively high in Croatia, it should be further supported and promoted. According to our investigation there is a possibility for further price reduction of diuretics and beta blockers in Slovenia. This is important as a tool to decrease costs of healthcare systems.

Abstract 937: Molecular dynamics of SrcS17 activation in chronic stress-induced tumor growth

Abstract Clinical studies have demonstrated that chronic stress can influence cancer progression. However, the underlying mechanisms are not fully understood. To determine the molecular drivers of downstream signaling networks activated in response to chronic stress, we performed a phosphoproteomic analysis and determined that the non-receptor tyrosine kinase, Src, was the key regulator of these networks. Since Src plays an important role in cancer biology, we examined the biological and clinical significance of Src in stress-mediated tumor growth. Norepinephrine (NE) rapidly activated SrcY419 in β-adrenergic receptor (ADRB) positive ovarian cancer cell lines, but not in ADRB-null cells. Confocal microscopy showed that Src was rapidly recruited to the cellular membrane after NE exposure in ADRB positive ovarian cancer cells. Furthermore, treatment with different ADRB agonists and blockers determined that ADRB2 is required for SrcY419 phosphorylation. Treatment with a cAMP agonist or PKA agonist/antagonists demonstrated that cAMP/PKA signaling is required for NE-induced Src activation. The unexpected Src activation via cAMP/PKA was found to be mediated by direct phosphorylation of SrcS17 following NE treatment. In Src-/- cells transiently expressing WT Src, NE caused SrcY419 phosphorylation, which was not observed when cells were transfected with a Src S17A construct. In order to investigate how S17 phosphorylation leads to Src activation, we performed molecular dynamic simulations and observed that upon SrcS17 phosphorylation, Src undergoes significant structural changes that expose its Y419 residue. To understand the functional consequences of stress-induced Src activation, we performed migration and invasion assays. Exposure to NE resulted in an increase in ovarian cancer cell migration and invasion that was completely abrogated by Src-targeted siRNA (P < 0.01). In various orthotopic mouse models of ovarian carcinoma, chronic restraint stress significantly increased tumor weights (P < 0.05). Increased tumor growth was completely blocked by Src silencing with Src siRNA-DOPC or by the non-specific beta-blocker, propranolol (P < 0.05). To test the clinical significance of our biological findings, we examined 91 epithelial ovarian cancer samples. Elevated pSrcY419 was associated with worse patient survival (P < 0.001), high tumoral NE levels (P < 0.001) and high scores on the Center for Epidemiologic Studies Depression Scale (P = 0.008). To examine the potential clinical impact of our findings, we investigated whether beta-blocker usage by patients affected cancer-related mortality. This analysis revealed that beta-blockers reduced mortality by 17% across all major cancer types and 14.6% among patients with ovarian and other gynecologic cancers. This work is the first to demonstrate that an ADRB-PKA-Src axis mediates the effect of chronic stress on tumor growth and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 937. doi:10.1158/1538-7445.AM2011-937

The deleterious effects of propranolol on patients with cirrhosis

We read with great interest the report by Serste et al.1 that describes an observational, prospective study of 151 patients with cirrhosis who did or did not receive beta-blocker therapy for prevention of gastrointestinal bleeding. In this study of propranolol therapy, Child-Pugh class C, hyponatremia, and renal impairment were found to be independent variables of mortality in patients with cirrhosis with refractory ascites. As a result, the authors suggest that propranolol should be contraindicated in these patients. Although the authors did not report the cardiac status of the patients, we would like to discuss their findings in this regard, upon the findings of two recent articles.2, 3 Krag et al.2 evaluated 24 patients with cirrhosis with a cardiac index (CI) above or below 1.5 L/minute/m2, and they found that patients with low CI showed significantly poorer survival than those with a higher CI. In addition, hyponatremia and renal impairment, which are independent variables of mortality in the study report by Serste et al., were found to be associated with lower CI.2 Krag et al. stated that a cardio-renal relation in cirrhosis is most likely the result of chronic circulatory stress combined with more acute events, such as bacterial translocation and systemic inflammatory response, which trigger a systemic response. This may lead to progression of a systolic failure with a decrease in CI, starting a vicious circle in which the decreased CI leads to accentuated arterial underfilling, decreased arterial pressure, and renal perfusion, resulting in deterioration of the renal function, which further enhances cardiac and renal deterioration. Recently, Sharma et al.3 investigated the effects of propranolol on normotensive and hypertensive patients with cirrhosis; they showed that CI significantly decreased after propranolol therapy in both groups. Based on these findings, we think that lowering effects of propranolol on CI and consecutively, development of hyponatremia and renal impairment, may explain the possible mechanism of deleterious effects of propranolol on survival in these patients. Finally, the common usage of beta-blockers for the prevention of variceal bleeding may change in the near future, at least in patients with severe cirrhosis, and band ligation and/or therapies that improve CI may be considered as emerging treatment options to improve survival. Cumali Efe M.D.*, Tugrul Purnak M.D. , Ersan Ozaslan M.D. , * Departments of Internal Medicine, Numune Research and Education Hospital, Ankara, Turkey, Gastroenterology, Numune Research and Education Hospital, Ankara, Turkey.

Beta 2 antagonism in acute respiratory failure

Post hoc analyses from the B-type natriuretic peptide for Acute Shortness of Breath Evaluation (BASEL)-II-ICU study suggest an association between beta-blocker usage at admission and improved mortality in patients treated in the intensive care unit for acute respiratory failure. Although this evidence is encouraging, there is a need for a phase 2 proof-of-concept randomized controlled trial of beta-blocker therapy in patients admitted with acute respiratory failure.

Adverse effects of beta adrenergic blockers during spinal anesthesia with 0.5% bupivacaine

Protocol for perioperative usage of beta blockers was used in only 9% of major clinics in the USA. It is a very common practice to discontinue beta blockers during the perioperative period or to maximally reduce their doses. The main purpose of this paper is to investigate the incidence of adverse effects of beta blockers during large-scale trauma and orthopedic surgeries in spinal anesthesia.

Perioperative β-blockers for vascular surgery patients

Perioperative beta-blocker therapy has been a heavily investigated and controversial topic during the past decade. Prior national consensus statements that recommended the routine use of these medications in patients undergoing high-risk surgical procedures have been called into question because of the results of recent clinical trials that involved heterogeneous groups of surgical patients. This article reviews the evidence for perioperative beta-blocker usage as it pertains to patients undergoing vascular surgery procedures. The weight of evidence suggests that beta-blockers lower the perioperative risk of myocardial ischemia or infarction and cardiovascular death among patients with clinical risk factors undergoing major vascular surgery. However, there appears to be a concurrent risk of adverse events associated with these medications if patients are not monitored properly during the perioperative period. Perioperative beta-blockers should continue to occupy a prominent role in the therapeutic armamentarium for improving outcomes among high-risk patients undergoing major vascular surgery.

Derivation and validation of a simple clinical risk-model in heart failure based on 6 minute walk test performance and NT-proBNP status – Do we need specificity for sex and beta-blockers?

It is unclear whether risk prediction strategies in chronic heart failure (CHF) need to be specific for sex or beta-blockers. We examined this problem and developed and validated the consequent risk models based on 6-minute-walk-test and NT-proBNP. The derivation cohort comprised 636 German patients with systolic dysfunction. They were validated against 676 British patients with similar aetiology. ROC-curves for 1-year mortality identified cut-off values separately for specificity (none, sex, beta-blocker, both). Patients were grouped according to number of cut-offs met (group I/II/III - 0/1/2 cut-offs). Widest separation between groups was achieved with sex- and beta-blocker-specific cut offs. In the derivation population, 1-year mortality was 0%, 8%, 31% for group I, II and III, respectively. In the validation population, 1-year rates in the three risk groups were 2%, 7%, 14%, respectively, after application of the same cut-offs. Risk stratification for CHF should perhaps take sex and beta-blocker usage into account. We derived and independently validated relevant risk models based on 6-minute-walk-tests and NT-proBNP. Specifying sex and use of beta-blockers identified three distinct sub-groups with widely differing prognosis. In clinical practice, it may be appropriate to tailor the intensity of follow-up and/or the treatment strategy according to the risk-group.

Use of β-blockers and effects on heart rate and blood pressure post-acute coronary syndromes: Are we on target?

beta-blockers have been shown to benefit patients after myocardial infarction by decreasing mortality, sudden cardiac death, and reinfarction. Although beta-blockers are recommended for all patients with acute coronary syndromes (ACS) without contraindications, a target heart rate (HR) is recommended only for patients with unstable angina/non ST-elevation myocardial infarction. A contemporary series documenting trends in beta-blocker usage and achieved HR and blood pressures (BP) is not available. The study objectives were to monitor trends in HR and BP in relation to beta-blocker use in a contemporary series of patients with ACS. In this observational study, 300 consecutive patients with proven ACS had HR and BP values collected hourly from admission until hospital discharge and averaged at multiple intervals throughout hospital stay. Data on baseline demographic characteristics, beta-blocker doses, and titration schedules, procedures performed, cardiac regimens, concurrent medical issues, and contraindications to therapy were collected. Only 5.3% achieved an average HR of 50 to 60 beat/min throughout the hospital stay. Overall, the average HR was 74 beat/min and average BP was 115/64 mm Hg. Admission daily doses of metoprolol averaged 58 mg compared to discharge daily doses of 88 mg; only 52% of patients had dosage increases. Although effective levels of BP were maintained during hospitalization for an ACS, target HRs were generally not achieved. Future studies are needed to determine the relationship between treatment objectives and clinical outcomes in the present era of ACS management.

Health-related Quality of Life in CKD Patients

Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument. Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities. These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

Natriuretic Peptides in Chronic Kidney Disease

B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) are biomarkers of cardiovascular disease that is common in patients with chronic kidney disease (CKD). Conflicting data on the influence of glomerular filtration rate (GFR) on BNP and NT-proBNP levels in CKD may stem from failure to account fully for the effects of coexistent cardiac disease, dysfunction, and volume overload. Prospective head-to-head comparison of plasma BNP and NT-proBNP in ambulatory euvolemic CKD patients with normal LV ejection fraction and no manifest cardiac or vascular disease. GFR was estimated by the Modification of Diet in Renal Disease formula, BNP and NT-proBNP measured using Abbott AxSYM and Roche Elecsys assays, respectively, and cardiac morphology and function assessed by transthoracic echocardiography. In 142 patients (42% female) of mean age 60 +/- 11 yr, mean left ventricular ejection fraction was 71% +/- 6%, GFR 38 +/- 14 ml/min per 1.73 m(2), and median BNP and NT-proBNP level 59 and 311 pg/ml, respectively. Multivariate predictors of NT-proBNP level were GFR, beta-blocker usage, LV mass index, and hemoglobin level. Plasma BNP was independently predicted by LV mass index and beta-blocker usage but not GFR. In the 74 patients without diastolic dysfunction, there was a significant rise in NT-proBNP but not BNP as GFR declined. Unlike NT-proBNP, plasma BNP level is relatively independent of GFR. BNP may therefore be the more appropriate biomarker to screen for cardiac dysfunction in CKD.

Reduction of in-hospital mortality among California hospitals meeting Leapfrog evidence-based standards for abdominal aortic aneurysm repair

The Leapfrog Group established evidence-based standards for abdominal aortic aneurysm (AAA) repair, including targets for case volume and perioperative beta-blocker usage. The purpose of this study was to determine whether meeting these benchmarks correlated with improved patient outcomes over time. We studied California hospitals that responded to consecutive Leapfrog Group Hospital Quality and Safety Surveys between 2000 and 2005. Survey results of compliance with Leapfrog standards were linked to patient outcomes for AAA repair using the California state discharge database for the corresponding years. A random-effects Poisson regression analysis was performed to measure the effect of meeting beta-blocker and case volume standards on hospital mortality and average length of stay after elective open and endovascular AAA repair (EVAR) during the early (2000-2002) and later (2003-2005) phase of Leapfrog implementation. Among 140 hospitals that performed open AAA repair, 25 (17.4%) met the Leapfrog case volume standard, 32 (22.2%) were compliant with routine perioperative beta-blocker use, 5 hospitals (3.5%) met both criteria, and 78 control hospitals failed to meet either standard. After controlling for temporal differences in hospital and patient characteristics, hospitals that implemented a policy for perioperative beta-blocker usage were found to have an estimated 51% reduction of in-hospital mortality (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < .05) after open AAA repair cases compared with control hospitals over time. There was no improvement in mortality outcomes over time, however, after open AAA repair in hospitals meeting case volume standards. Among 111 California hospitals in which EVAR was performed, there was an estimated 61% reduction of in-hospital mortality over time (relative risk, 0.39; 95% confidence interval, 0.07-1.80) among hospitals meeting Leapfrog case volume standards compared with control hospitals, although these results did not reach statistical significance. Finally, there was no reduction in length of hospital stay over time after either EVAR or open AAA repair for hospitals meeting Leapfrog standards compared with control hospitals. This population-based study supports the effectiveness of meeting Leapfrog AAA repair standards towards improving mortality outcomes over time and suggests that their impact depends upon procedure type. Further studies are needed to help promote the standardization of evidence-based measures that may improve vascular surgery outcomes.

Long-Term Disease Management of Patients With Coronary Disease by Cardiac Rehabilitation Program Staff

Randomized-clinical trials have demonstrated the benefits of disease management for patients with coronary disease. It is not known if long-term disease management in routine clinical practice provided by cardiac rehabilitation (CR) program staff is possible. The goal of this study was to evaluate the feasibility and clinical benefits of a 3-year disease-management program in the setting of an outpatient CR facility. Consecutive patients (n = 503) referred to CR and who were available for long-term follow-up served as subjects. After a phase II CR program, disease managers assessed secondary-prevention goals every 3 to 6 months via face-to-face meetings with each patient. Outcome measures included use of cardioprotective medications, coronary risk factors, amount of habitual exercise training, and all-cause mortality. At 3 years, aspirin usage was 91%, statin usage 91%, beta-blocker usage 78%, and angiotensin-converting enzyme inhibitor usage 76%. Low-density lipoprotein cholesterol was 90 +/- 23 mg/dL, systolic blood pressure was 126 +/- 19 mm Hg, and body mass index was 29.0 +/- 5.1 kg/m2. Exercise training averaged 139 +/- 123 minutes per week. Annual mortality was 1.9%. There were no differences (P > .05) in medication usage or low-density lipoprotein cholesterol for men versus women, or for age below 65 years versus age 65 years or greater. Long-term disease management of patients with coronary disease in routine clinical practice by CR program staff is feasible and effective in achieving and maintaining secondary-prevention goals. Overweight remains a prevalent and persistent risk factor. We advocate expansion of CR programs into long-term coronary disease-management programs.

Depressive Symptoms Predict Heart Rate Recovery After Exercise Treadmill Testing in Patients With Coronary Artery Disease: Results From the Psychophysiological Investigations of Myocardial Ischemia Study

Depression is associated with increased risk of death among patients with coronary disease. Cardiovascular autonomic dysregulation may be one of the mechanisms by which depression exerts its effects on cardiovascular function. The purpose of this study was to determine whether depressive symptoms are associated with low heart rate variability (HRV) and prolonged HR recovery after exercise testing in patients with coronary artery disease (CAD). The Psychophysiological Investigation of Myocardial Ischemia (PIMI) was a large, multicenter study designed to assess psychological and physiological correlates of stress in patients with CAD. One hundred and eighty-eight patients with CAD as evidenced by at least 50% blockage of one major artery and a previous positive exercise stress test were included in this study. Patients included in this report were not taking beta blockers. Cardiovascular functioning was assessed by a modified Bruce protocol treadmill stress test. Measures of psychological functioning, including the Beck Depression Inventory (BDI), were also obtained. BDI scores were negatively correlated with HR recovery (r = -0.15, p = .04). Depression scores accounted for 3.5% of the variance in HR recovery when controlling for participant age (p < .01). Depressive symptoms were related to two HRV indices (ultra-low frequency, high frequency). Depressive symptoms are associated with cardiovascular autonomic nervous system dysfunction as assessed by HR recovery. This relationship is not merely due to an association of depression severity with beta blocker usage or a failure of depressed patients to achieve an adequate chronotropic response.

Impact of Duty Hours Restrictions on Quality of Care and Clinical Outcomes

Background In July 2003, the Accreditation Council for Graduate Medical Education instituted residency duty-hours requirements in response to growing concerns regarding clinician fatigue and the incidence of medical errors. These changes, which limited maximum continuous hours worked and total hours per week, often resulted in increased discontinuity of care. The objective of this study was to assess the impact of the duty-hours restrictions on quality of care and outcomes of patients with acute coronary syndrome. Methods We performed a retrospective analysis of 1003 consecutive patients with acute coronary syndrome admitted to the University of Michigan Hospital between July 2002 and June 2004. Patients were stratified by hospital admission during academic year 2002-2003 (pre-duty-hours changes, n = 572) and academic year 2003-2004 (post-duty-hours changes, n = 431). Main outcome measures included differences in adherence to quality indicators, length of stay, and in-hospital and 6-month adverse events. Results Post-duty-hours changes, there was an increase in the usage of beta-blockers (85.8% vs 93.8%, P <.001), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (65.7% vs 71.8%, P = .046), and statins (76.2% vs 84.0%, P = .002) at time of discharge. Length of stay decreased from 3.1 days to 2.8 days, P = .002. There was no difference in in-hospital mortality (4.2% vs 2.8%, P = .23). Six-month mortality (8.0% vs 3.8%, P = .007) and risk-adjusted 6-month mortality (odds ratio 0.53, 95% confidence interval, 0.28-0.99, P = .05) decreased after the duty-hours changes. Conclusions Implementation of the Accreditation Council for Graduate Medical Education residency duty-hours restrictions on an academic inpatient cardiology service was associated with improved quality of care and efficiency in patients admitted with acute coronary syndrome. In addition, improved efficiency did not adversely impact patient outcomes, including mortality.

Predictors of Therapeutic Response to Beta-blockers in Patients with Heart Failure in Taiwan

Chinese are more sensitive to beta-blockers than Caucasians. However, data regarding beta-blocker therapy in heart failure (HF) patients in Taiwan are lacking. We aimed to evaluate the improvement of left ventricular function and the potential predictors of response to beta-blocker therapy in Taiwanese HF patients. We enrolled 34 HF patients with baseline left ventricular ejection fraction (LVEF) </= 40%. Beta-blockers were titrated up to the maximum tolerable dose. LVEF prior to beta-blocker usage and at the stable dose were obtained. We also sequenced the entire gene encoding beta1-adrenoceptor to assess the relationships between LVEF improvement and gene polymorphisms. Beta-blocker therapy (25 +/- 22 months) with a mean stable dose of 12 +/- 8 mg carvedilol/day significantly improved LVEF (from 28 +/- 8% to 40 +/- 15%, p < 0.001). Stepwise multiple linear regression analysis identified dilated cardiomyopathy (beta = 18.32, p = 0.0004), baseline LVEF (beta = -0.85, p = 0.0020), use of amiodarone (beta = -22.58, p = 0.0034) and square of digoxin dose (beta = -314.25, p = 0.0059) at stable beta-blocker dose as independent predictors of LVEF improvement, where beta is the estimated regression coefficient. We did not find any novel variant of beta1-adrenoceptor gene other than those previously reported at codons 49 and 389, with the allele distributions similar to those found in Caucasians, and these polymorphisms did not imply therapeutic response to beta-blocker. We demonstrated the therapeutic effects of beta-blockers in Taiwanese HF patients with a dose lower than what has been reported in Western people. Moreover, patients with the etiology of dilated cardiomyopathy or lower baseline LVEF predicted a greater LVEF improvement. The beta1-adrenoceptor gene polymorphisms were not responsible for the difference in sensitivity to beta-blockers in this Taiwanese population.

244 Derivation and validation of a clinical risk-model in heart failure based on 6-min walk test performance and NT-proBNP status

Introduction:Chronic heart failure (CHF) trials have frequently reported that 6-min walk test (6-MWT) distance and NT-proBNP status are important prognostic indicators. We wished to provide a risk profile, adjusted by sex and beta-blocker (BBL) usage, from two large cohorts of patients in Germany and the UK. Methods:We included 1100 patients with systolic CHF from the University Hospital Heidelberg, Germany in a derivation cohort and validated these against 676 patients with similar aetiology from the Department of Academic Cardiology, University of Hull, UK. Serial log-rank analysis identified and validated the individual cut-off for optimal risk stratification for all-cause mortality according to sex and BBL status. Patients at increased risk according to 6-MWT distance were also stratified by NT-proBNP status. Results: In both cohorts, 6-MWT was an independent predictor of mortality. Patients not prescribed BBL with a 6-MWT distance of ≤430m (males) and ≤360m (females) had a higher all-cause mortality risk. For patients prescribed BBL, risk cut-points were adjusted accordingly: ≤370m (males), and≤330m (females). Patients with an adverse 6-MWT had a risk profile based on NT-proBNP status of ≤650ng/l (males) and ≤710ng/l (females). Three clinical risk groups were formed with a 1-year mortality of 3.6%, 9.6% and 24.4%, respectively (P<0.0001).

ASSOCIATION BETWEEN PSYCHOTROPIC DRUG USE AND HEART FAILURE THERAPY IN ELDERLY LONG‐TERM CARE RESIDENTS

ASSOCIATION BETWEEN PSYCHOTROPIC DRUG USE AND HEART FAILURE THERAPY IN ELDERLY LONG‐TERM CARE RESIDENTS

Reducing the Risk of Sudden Death in Heart Failure With β-Blockers

Heart failure (HF) is a serious cardiovascular syndrome that affects nearly 5 million people in the United States. A review of clinical data demonstrates that sudden cardiac death (SCD) accounts for approximately one-third of all HF deaths. This fatal outcome typically involves an unexpected electrical event leading to sustained cardiac arrhythmias resulting in cardiovascular collapse. A systematic review of the literature was performed to serve as the basis for this review. Factors contributing directly to incidence of SCD in the HF population may include significant remodeling of the left ventricle (hypertrophy, dilation, and fibrosis) in addition to increased sympathetic activation. Using specific therapies to limit these mechanisms are beneficial in the HF patient by preventing SCD. Beta-blockers play a key role in the prevention of SCD for patients with HF by limiting the effects of circulating norepinephrine and by reducing left ventricular remodeling. This review outlines the potential mechanisms and contributing factors of SCD in patients with HF and the impact of beta-blocker usage in the prevention of this fatal outcome for this growing patient population.

Prognostic value of the 6 min walk test and self-perceived symptom severity in older patients with chronic heart failure

The 6 min walk test (6-MWT) is a simple and popular test for evaluating functional status in patients with chronic heart failure (CHF). However, the prognostic value of the 6-MWT in a large, representative sample of CHF patients, and in patients with different degrees of left ventricular systolic dysfunction (LVSD) remains unclear. Of an initial population of 1592 patients, 212 died representing a crude death rate of 13.3%. In surviving patients, the median time to follow-up period was 36.6 months [inter-quartile range (IQR) 28-45 months]. Five variables remained independent predictors of all-cause mortality; decreasing 6-MWT distance, self-perceived signs of breathlessness at night (SOBAN), beta-blocker usage, elevated log NT-proBNP, and reduced haemoglobin concentration. We also dichotomized our analysis by LVSD status (<or=mild LVSD or >mild LVSD). For patients with >mild LVSD, 6-MWT remained an important prognostic indicator but not in patients with <or=mild LVSD. The 6-MWT is an important independent predictor of mortality in CHF patients, and this was especially evident in patients with >mild LVSD. The 6-MWT provides little prognostic utility in patients with <or=mild LVSD. While log NT-proBNP was the most potent independent predictor, an additive prognostic effect was evident with the additional selection of 6-MWT. Patients' self-perceived symptoms, especially SOBAN was an independent predictor of mortality in our patients.

Funnel plots, performance variation and the Myocardial Infarction National Audit Project 2003–2004

BackgroundClinical governance requires health care professionals to improve standards of care and has resulted in comparison of clinical performance data. The Myocardial Infarction National Audit Project (a UK cardiology dataset) tabulates its performance. However funnel plots are the display method of choice for institutional comparison. We aimed to demonstrate that funnel plots may be derived from MINAP data and allow more meaningful interpretation of data.MethodsWe examined the attainment of National Service Framework standards for all hospitals (n = 230) and all patients (n = 99,133) in the MINAP database between 1st April 2003 and 31st March 2004. We generated funnel plots (with control limits at 3 sigma) of Door to Needle and Call to Needle thrombolysis times, and the use of aspirin, beta-blockers and statins post myocardial infarction.ResultsOnly 87,427 patients fulfilled criteria for analysis of the use of secondary prevention drugs and 15,111 patients for analysis by Door to Needle and Call to Needle times (163 hospitals achieved the standards for Door to Needle times and 215 were within or above their control limits). One hundred and sixteen hospitals fell outside the 'within 25%' and 'more than 25%' standards for Call to Needle times, but 28 were below the lower control limits. Sixteen hospitals failed to reach the standards for aspirin usage post AMI and 24 remained below the lower control limits. Thirty hospitals were below the lower CL for beta-blocker usage and 49 outside the standard. Statin use was comparable.ConclusionFunnel plots may be applied to a complex dataset and allow visual comparison of data derived from multiple health-care units. Variation is readily identified permitting units to appraise their practices so that effective quality improvement may take place.