Left Ventricular global longitudinal strain predicts heart failure readmission in acute decompensated heart failure.

BACKGROUND: The goal of this study was to determine if left ventricular (LV) global longitudinal strain (GLS) predicts heart failure (HF) readmission in patients with acute decompensated heart failure. METHODS AND RESULTS: Two hundred ninety one patients were enrolled at the time of admission for acute decompensated heart failure between January 2011 and September 2013. Left ventricle global longitudinal strain (LV GLS) by velocity vector imaging averaged from 2, 3 and 4-chamber views could be assessed in 204 out of 291 (70%) patients. Mean age was 63.8 ± 15.2 years, 42% of the patients were males and 78% were African American or Hispanic. Patients were followed until the first HF hospital readmission up to 44 months. Patients were grouped into quartiles on the basis of LV GLS. Kaplan-Meier curves showed significantly higher readmission rates in patients with worse LV GLS (log-rank p < 0.001). After adjusting for age, sex, history of ischemic heart disease, dementia, New York Heart Association class, LV ejection fraction, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, systolic and diastolic blood pressure on admission and sodium level on admission, worse LV GLS was the strongest predictor of recurrent HF readmission (p < 0.001). The ejection fraction was predictive of readmission in univariate, but not in multivariate analysis. CONCLUSION: LV GLS is an independent predictor of HF readmission after acute decompensated heart failure with a higher risk of readmission in case of progressive worsening of LV GLS, independent of the ejection fraction.

Circulating Procollagen Type III N-Terminal Peptide and Mortality Risk in African Americans With Heart Failure.

BACKGROUND: Procollagen type III N-terminal peptide (PIIINP) is a biomarker of cardiac fibrosis that is associated with heart failure prognosis in whites. Its prognostic significance in African Americans is unknown. We sought to determine whether PIIINP is associated with outcomes in African Americans with heart failure. METHODS AND RESULTS: Blood was collected from 138 African Americans with heart failure for determining PIIINP and genetic ancestry, and patients were followed prospectively for death or hospitalization for heart failure. PIIINP was inversely correlated with West African ancestry (R(2) = 0.061; P = .010). PIIINP > 4.88 ng/mL was associated with all-cause mortality on univariate (hazard ratio [HR] 4.9, 95% confidence interval [CI] 2.2-11.0; P < .001) and multivariate (HR 5.8; 95% CI 1.9-17.3; P = .002) analyses over a median follow-up period of 3 years. We also observed an increased risk for the combined outcome of all-cause mortality or hospitalization for heart failure with PIIINP > 4.88 ng/mL on univariate (HR 2.6, 95% CI 1.6-5.0; P < .001) and multivariate (HR 2.4, 95% CI 1.2-4.7; P = .016) analyses. CONCLUSIONS: High circulating PIIINP is associated with poor outcomes in African Americans with chronic heart failure, suggesting that PIIINP may be useful in identifying African Americans who may benefit from additional therapy to combat fibrosis as a means of improving prognosis.

The Role of External Fixation in the Treatment of Distal Radius Fractures.

There are numerous internal fixation (IF) options available for distal radius fractures (DRFs). The choice of fixation method depends on factors such as fracture morphology, soft tissue integrity, the patient's clinical status, and the surgeon's training. While volar plate fixation has become the primary approach for addressing these fractures, alternative IF methods like K-wire fixation, fragment-specific fixation, and dorsal bridge plating continue to be effective. Despite the versatility of IF, there are certain clinical situations where prompt and conclusive management through open reduction and internal fixation (ORIF) is not suitable. These instances include the treatment of polytraumatized patients, individuals with compromised soft tissues, or those medically unstable to tolerate lengthy anesthesia. In such cases, proficiency in closed reduction and external fixation (EF) proves invaluable. Being able to identify these clinical scenarios and comprehend the efficacy and safety of EF in addressing DRFs is valuable for any surgeon handling such injuries.

Hospital compliance with performance measures and 30-day outcomes in patients with heart failure.

BACKGROUND: In 2005, the American College of Cardiology/American Heart Association published performance measures to provide a standard of care for hospitalized patients with heart failure (HF). Despite increasing compliance with these measures, hospital mortality and readmission rates remain stagnant. Whether compliance with HF performance measures improves patient outcomes at the hospital level is unclear. METHODS: We evaluated compliance with HF performance measures at 3,655 US hospitals. Patients admitted with a diagnosis of HF in 2008 were identified using the US Department of Health and Human Services Hospital Compare database. Compliance with 4 specific performance measures was examined: evaluation of left ventricular systolic function, administration of angiotensin-converting enzyme inhibitor I or angiotensin-receptor blocker for left ventricular systolic dysfunction, offering smoking cessation advice and counseling, and providing discharge instructions. Thirty-day mortality and readmission rate were recorded. RESULTS: Hospitals reporting greater compliance with the 4 performance measures had significantly lower 30-day mortality rates. However, these hospitals were also located in areas of higher socioeconomic status and treated higher volumes of patients with HF. After adjusting for socioeconomic and hospital factors, only evaluation of left ventricular systolic function was associated with lower 30-day mortality, and evaluation of left ventricular systolic function and smoking cessation counseling were associated with lower readmission rates. CONCLUSIONS: We found that socioeconomic factors and hospital volume were stronger predictors of mortality than compliance with HF performance measures. After adjusting for socioeconomic factors and hospital volume, only 1 of the 4 performance measures was associated with lower 30-day mortality and 2 were associated with lower readmissions.

Flexible diuretic titration in chronic heart failure: where is the evidence?

BACKGROUND: Several sets of heart failure (HF) consensus/guideline statements support the use of a flexible diuretic dosing regimen for HF outpatient management of fluid overload-related signs and symptoms. However, despite the widespread acceptance of such an approach, the evidence supporting the effectiveness of this approach in improving clinical outcomes is unknown. The primary objective of this manuscript was to summarize and review the evidence supporting the use of a flexible diuretic regimen in the management of outpatient heart failure patients. METHODS AND RESULTS: A systematic review was performed, and 9 studies were identified relevant to the question of flexible diuretic titration in the setting of chronic heart failure. Among the 9 studies, 5 were randomized. Three of the randomized trials included flexible diuretic titration as part of a broader multifaceted disease management program, and only 2 were designed to specifically evaluate the sole contribution of flexible diuretic titration. Collectively, data from all of the studies reviewed supported the idea that flexible and individualized diuretic dosing is potentially associated with reduced emergency room visits, reduced rehospitalization, and improved quality of life in HF patients with reduced ejection fraction. CONCLUSIONS: To date, only 2 randomized clinical studies were identified that were designed to determine the effects of a flexible diuretic dosing regimen in outpatient HF patients with reduced ejection fraction. Data are lacking in HF patients with preserved ejection fraction. There is a critical need to test this strategy in well designed prospective randomized clinical trials.

Management of anemia in heart failure.

PURPOSE OF REVIEW: Anemia is a relatively common finding in heart failure. Anemia in heart failure patients has been independently associated with reduced exercise tolerance, increased heart failure hospitalizations and increased all-cause mortality. Anemia would appear to be a reasonable treatment target for patients with heart failure. The review will discuss the potential causes of anemia in heart failure patients and give an up-to-date overview of treatment trials. RECENT FINDINGS: Studies assessing the pathophysiology of anemia in heart failure patients have recently demonstrated the potential importance of iron deficiency, abnormal iron metabolism and hemodilution. Treatment studies have focused on the use of erythropoiesis-stimulating agents, with recent trials showing mixed results. SUMMARY: Despite initial studies indicating a possible beneficial effect of erythropoiesis-stimulating agents in the treatment of anemic heart failure patients, clinical trial data, to date, have failed to show convincing evidence for morbidity or mortality benefit, and information on the long-term safety is lacking. Ongoing large-scale trials will have the potential to provide such information in the future.

Six minute walk test predicts long-term all-cause mortality and heart failure rehospitalization in African-American patients hospitalized with acute decompensated heart failure.

BACKGROUND: The prognostic value of the 6-minute walk test (6MWT) has been described in patients with heart failure (HF); however, limited data are available in an African-American (AA) population. We prospectively evaluated the usefulness of the 6MWT in predicting mortality and HF rehospitalization in AA patients with acute decompensated HF. METHODS AND RESULTS: Two hundred AA patients (63.1% men, mean age 55.7 +/- 12.9 years) with acute decompensated HF were prospectively studied. Patients were followed to assess 40-month all-cause mortality and 18-month HF rehospitalization. The median distance walked on the 6MWT was 213 m. Of the 198 patients with available mortality data, 59 patients (29.8%) died. Of the 191 patients with available rehospitalization data, 114 (59.7%) were rehospitalized for worsening HF. For patients who walked 200 m (P = .001). For patients who walked 200 m (P = .027). Multivariate Cox regression analysis showed that 6MWT distance

Enhancing Participation in Cardiac Rehabilitation: A Question of Proximity and Integration of Outpatient Services.

Numerous investigations have established the strong clinical utility of cardiac rehabilitation, while clinical guidelines continually call for a high level of referral and participation. Historically, medical facilities have faced challenges referring eligible patients to cardiac rehabilitation, enrolling only a small portion of those receiving referral. Consequently, less than ~10% of qualifying patients receive any amount of cardiac rehabilitation. This sobering figure has prompted many efforts to identify barriers to referral as well as enrollment and accordingly propose strategies to bolster participation rates. Although reports have highlighted improvements through focused approaches, enrollment rates still lag behind the goal of reaching 70% by 2022, proposed by the Million Hearts Cardiac Rehabilitation Collaborative. An area of inquiry that has received little to no attention in this effort has been the influence of proximity between physician-driven outpatient clinics and cardiac rehabilitation facilities. In this report we outline the development and design of a clinical faculty practice aimed to maintainclose geographical proximity between our physicianclinic and the cardiac rehabilitation area. We also propose that our impressive enrollment rates of 57% within our facility and 73% when including patients that started alternative exercise programs were likely due to establishing a close proximity between the respective practices.

Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.

The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes ( P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients ( P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype ( P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.

Racial Differences in Characteristics and Outcomes of Patients With Heart Failure and Preserved Ejection Fraction in the Treatment of Preserved Cardiac Function Heart Failure Trial.

BACKGROUND: Black patients have been shown to have different baseline characteristics and outcomes compared with nonblack patients in cohort studies. However, few studies have focused on heart failure (HF) with preserved ejection fraction (HFpEF) patients. We aimed to determine the difference in cardiovascular outcomes in black and nonblack patients with HFpEF and to determine the relative efficacy and safety of spironolactone in black and nonblack patients. METHODS AND RESULTS: Patients with HFpEF, randomized to spironolactone versus placebo in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in North and South America, were grouped according to self-described black and nonblack race. Black HFpEF patients (n=302) were younger and were more likely to have diabetes mellitus and hypertension than nonblack patients but had similar HFpEF severity. Black patients had higher risk for the primary outcome (hazard ratio [HR], 1.34; 95% confidence interval, 1.06-1.71; P=0.02) and first HF hospitalization (HR, 1.51; 95% confidence interval, 1.167-1.97; P=0.002)], but no significant difference in cardiovascular mortality risk (HR, 0.78; 95% confidence interval, 0.51-1.20; P=0.326). In black and nonblack patients, randomization to spironolactone conferred similar efficacy in the primary outcome (HR, 0.83 versus 0.79; P for interaction=0.49), HF hospitalization (HR, 0.67 versus 0.82; P for interaction=0.76), and cardiovascular mortality (P for interaction=0.19). The risk of hyperkalemia and worsening renal function with spironolactone and study drug adherence were also similar. CONCLUSIONS: Black patients with HFpEF have a higher HF hospitalization risk than nonblack patients, but spironolactone is similarly effective and safe in both groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Cancer antigen-125 and risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Cancer antigen-125 (Ca-125) is traditionally recognised as a tumour marker and its role in cardiovascular diseases has been studied only in recent years. Whether Ca-125 is elevated in patients with atrial fibrillation (AF) and its levels predict the risk of AF remains controversial. Therefore, we conducted a systematic review and meta-analysis of the association between Ca-125 levels and AF. METHODS: PubMed and EMBASE databases were searched until 1 June 2017 for studies that evaluated the association between Ca-125 and AF. Inclusion criteria included studies that compare Ca-125 in patients with and without AF, or those reporting HRs/ORs for risk of AF stratified by Ca-125 levels. RESULTS: A total of 39 entries were retrieved from the databases, of which 10 studies were included in the final meta-analysis. Ca-125 was significantly higher in patients with AF compared with those in sinus rhythm (mean difference=16 U/mL, 95% CI 2 to 30 U/mL, P<0.05; I2: 98%). Ca-125 significantly increased the risk of AF (HR: 1.39, 95% CI 1.06 to 1.82, P<0.05; I2: 84%). CONCLUSION: Ca-125 was significantly higher in patients with AF than in those in sinus rhythm, and high Ca-125 is predictive of AF occurrence. However, the high heterogeneity observed means there is an uncertainty in the relationship between Ca-125 and AF, which needs to be confirmed by larger prospective studies.

Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.

STUDY OBJECTIVE: To determine whether beta-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure. DESIGN: Prospective clinical study. SETTING: Two heart failure centers. PATIENTS: Eighty-eight spironolactone-naïve patients with heart failure who were taking beta-blockers. INTERVENTION: In a subset of 29 patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to 25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (> or = 50% of recommended target dose) of beta-blockers. Patients receiving low-dose beta-blockers had higher mean +/- SD PIIINP concentrations (6.6 +/- 3.5 vs 4.9 +/- 2.6 microg/L, p=0.03) and tended to have higher PINP concentrations (74.0 +/- 44.1 vs 57.1 +/- 28.6 microg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low-dose (9 patients) and high-dose (20 patients) beta-blocker groups. Low beta-blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] -14.3 microg/L [-9.8 to -19.3 microg/L] vs -2.5 microg/L [5.9 to -9.8 microg/L], p=0.02) and PIIINP (-1.4 microg/L [-0.9 to -2.4 microg/L] vs 0.1 microg/L [0.9 to -1.3 microg/L], p=0.045) with spironolactone therapy than high beta-blocker doses. In addition, 100% of the patients in this subset taking low-dose beta-blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis. CONCLUSION: Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of beta-blocker dosages, at least in terms of its effects on cardiac remodeling.

Markers of cardiac collagen turnover are similar in patients with mild and more severe symptoms of heart failure.

Cardiac fibrosis plays an important role in the pathophysiology of heart failure. The authors sought to determine whether biomarkers of cardiac fibrosis for milder clinical degrees of heart failure are comparable to those of more advanced disease. Procollagen types I and III amino-terminal peptides (PINP and PIIINP) and type I collagen telopeptide (ICTP) were compared between aldosterone-antagonistnaive patients with heart failure and New York Heart Association class I or II (n=22/23) and class III or IV (n=42/3) symptoms. Median (interquartile) range concentrations of PINP (63.3 [44.2-88.8] vs 48.6 [37.8-74.9] microg/L), ICTP (7.0 [5.4-16.8] vs 6.5 [4.7-12.7] microg/L), and PIIINP (4.7 [3.2-7.0] vs 4.7 [2.9-7.3] microg/L) were comparable between patients with mild and moderate to severe disease, respectively. These data suggest that patients with mild heart failure may have similar degrees of cardiac fibrosis to patients with more severe disease and support the examination of antifibrotic therapy, including aldosterone antagonists, in milder degrees of heart failure.

Left ventricular global longitudinal strain predicts mortality and heart failure admissions in African American patients.

BACKGROUND: Several studies have demonstrated the importance of left ventricular (LV) global longitudinal strain (GLS) as a reliable prognostic indicator in patients with heart failure (HF). These studies have included few African American (AA) patients, despite the growing prevalence and severity of HF in this patient population. HYPOTHESIS: LV GLS predicts long-term HF admission and all-cause mortality in AA patients with chronic HF on optimal guideline-directed medical therapy (GDMT). METHODS: We enrolled 207 AA adults, age 56 ± 14.5 years, with New York Heart Association (NYHA) class I through III HF on optimal GDMT from the University of Illinois HF clinic between November 2001 and February 2014. LV GLS was assessed by velocity vector imaging using 2-, 3-, and 4-chamber views. Patients were followed for HF admissions and death for 3 ± 3.0 years. LV GLS value of -7.95 was used as the optimal cutoff point that maximizes sensitivity and specificity RESULTS: LV GLS < -7.95% was significantly associated with higher all-cause mortality and HF admissions in Kaplan-Meier survival curves (log-rank P < 0.001). After incorporation in multivariate Cox proportional hazard models, GLS < -7.95% was found to be an independent predictor of all-cause mortality (hazard ratio [HR] = 4.04; 95% confidence interval [CI]: 1.07-15.32; P = 0.04] and HF admissions (HR = 3.86; 95% CI: 1.38-10.77; P = 0.010). CONCLUSIONS: In AA patients with chronic stable HF on GDMT, more impaired LV GLS (< -7.95%) is a strong and independent predictor of long-term all-cause mortality and HF admissions.

Using impedance cardiography to assess left ventricular systolic function via postural change in patients with heart failure.

For the diagnosis and management of heart failure, it would be useful to have a simple point-of-care test for assessing ventricular function that could be performed by a nurse. An impedance cardiography (ICG) parameter called systolic amplitude (SA) can serve as an indicator of left ventricular systolic function (LVSF). This study tested the hypothesis that patients with normal LVSF should have a significant increase in SA in response to an increase in end-diastolic volume caused by postural change from sitting upright to supine, while patients with depressed LVSF associated with heart failure should have a minimal increase or a decrease in SA from upright to supine. ICG data were obtained in 12 patients without heart disease and with normal LVSF and 18 patients with clinically diagnosed heart failure. Consistent with the hypothesis, patients with normal LVSF had a significant increase in SA from upright to supine, whereas heart failure patients had a minimal increase or a decrease in SA from upright to supine. This ICG procedure may be useful for monitoring the trend of patient response to titration of beta blockers and other medications. ICG potentially could be used to detect worsening LVSF and provide a means of measurement for adjusting treatment.

Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure.

To determine whether clinical parameters alone can differentiate normal versus decreased systolic left ventricular function in patients with heart failure. Detailed clinical data were collected prospectively from 225 consecutive patients who were hospitalized with heart failure. Findings in patients with normal (ejection fraction > or =45%) or decreased (ejection fraction <45%) left ventricular function were compared. Systolic function was normal in 104 patients (46%) and decreased in 121 patients (54%). Patients with normal function were older (mean [+/- SD] age, 59 +/- 13 years vs. 54 +/- 13 years, P = 0.007) and more likely to be female (56% vs. 35%, P = 0.001), obese (body mass index > or =30 kg/m(2), 62% vs. 48%, P = 0.04), have marked systolic (> or =160 mm Hg, 50% vs. 27%, P <0.001) and diastolic (> or =110 mm Hg, 25% vs. 13%, P = 0.02) hypertension, and use calcium antagonists (34% vs. 14%, P = 0.001). Patients with decreased function were more likely to use alcohol (37% vs. 20%, P = 0.007), angiotensin-converting enzyme (ACE) inhibitors (85% vs. 62%, P <0.001), and digoxin (57% vs. 27%, P <0.001); and more likely to have tachycardia (51% vs. 32%, P = 0.004), rales (89% vs. 80%, P = 0.05), electrocardiographic left ventricular hypertrophy (42% vs. 22%, P = 0.002), left atrial abnormality (52% vs. 22%, P <0.001), or flow cephalization on chest radiograph (91% vs. 79%, P = 0.02). Only sex, tachycardia, and use of digoxin and ACE inhibitors were associated with ventricular function in multivariable analysis. However, the sensitivity, specificity, and predictive values for all clinical variables were low. Differences in clinical parameters in heart failure patients with decreased versus normal systolic function cannot predict systolic function in these patients, supporting recommendations that heart failure patients should undergo specialized testing to measure ventricular function.

Association of aldosterone synthase polymorphism (CYP11B2 -344T>C) and genetic ancestry with atrial fibrillation and serum aldosterone in African Americans with heart failure.

The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n = 126), serum was also collected for determination of circulating aldosterone. The CYP11B2 -344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 -344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60-98.4, p = 0.0150, empirical p = 0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p = 0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r = -0.19, p = 0.037). The CYP11B2 -344CC genotype was also overrepresented among patients with extreme aldosterone elevation (≥90th percentile, p = 0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 -344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans.

Feasibility of implementing a comprehensive warfarin pharmacogenetics service.

STUDY OBJECTIVE: To determine the procedural feasibility of a pharmacist-led interdisciplinary service for providing genotype-guided warfarin dosing for hospitalized patients newly starting warfarin. DESIGN: Prospective observational study. SETTING: A 438-bed tertiary care hospital affiliated with a large academic institution. PATIENTS: Eighty patients who started warfarin therapy and were managed by a newly implemented pharmacogenetics service. INTERVENTION: All patients received routine warfarin genotyping and clinical pharmacogenetics consultation. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were percentage of genotype-guided dose recommendations available prior to the second warfarin dose and adherence of the medical staff to doses recommended by the pharmacogenetics service. Of 436 genotype orders placed during the first 6 months of the service, 190 (44%) were deemed appropriate. For the 80 patients on the service who consented to data collection, 76% of the genotypes were available prior to the second warfarin dose. The median (range) time from genotype order to genotype result was 26 hours (7-80 hrs), and the time to genotype-guided dose recommendation was 30 hours (7-80 hrs). A total of 73% of warfarin doses ordered by the medical staff were within 0.5 mg of the daily dose recommended by the pharmacogenetics consult service. CONCLUSION: Providing routine genotype-guided warfarin dosing supported by a pharmacogenetics consult service is feasible from a procedural standpoint, with most genotypes available prior to the second warfarin dose and good adherence to genotype-guided dose recommendations by the medical staff.

Comparison of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure: a cost-effectiveness analysis.

STUDY OBJECTIVE: To compare lifetime costs and health outcomes of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure from the third-party payer perspective. DESIGN: A Markov decision analysis model constructed from costs, utility, and transition probability inputs obtained from randomized clinical trials and publically available databases. PATIENTS: A simulated cohort aged 65 years or older with persistent or paroxysmal atrial fibrillation and heart failure. MEASUREMENTS AND MAIN RESULTS: Markov states for rhythm control were cardioversion plus amiodarone and maintenance amiodarone, and those for rate control were ß-blocker, digoxin, and calcium channel blocker. Transition states included treatment success, hospitalizations for atrial fibrillation and/or heart failure, and severe adverse effects. Economic inputs included cost for drugs, cost of hospitalizations for atrial fibrillation and/or heart failure, and cost of management of severe adverse effects. Costs were measured in 2009 U.S. dollars, and clinical outcomes in quality-adjusted life-years (QALYs). One-way and multivariable sensitivity analyses were conducted. Uncertainty intervals (UIs) were obtained from probabilistic sensitivity analyses. Rate control was found to be less costly and more effective than rhythm control. Base case and probabilistic sensitivity analyses cost and effectiveness values for rate control were $7231 (95% UI $5517-9016) and 2.395 QALYs (95% UI 2.366-2.424 QALYs); whereas those for rhythm control were $16,291 (95% UI $11,033-21,434) and 2.197 QALYs (95% UI 2.155-2.237 QALYs). No critical values were found for any model parameters in the one-way sensitivity analyses. The cost-effectiveness acceptability curves showed that rate control was considered cost-effective in 100% of cases at willingness-to-pay ratios between $0 and $200,000/QALY. CONCLUSION: Rate control is less costly and more effective than rhythm control and should be the initial treatment for atrial fibrillation among patients with coexisting heart failure.