Blood pressure control among US veterans: a large multiyear analysis of blood pressure data from the Veterans Administration health data repository.

BACKGROUND: Hypertension treatment and control remain low worldwide. Strategies to improve blood pressure control have been implemented in the United States and around the world for several years. This study was designed to assess improvement in blood pressure control over a 10-year period in a large cohort of patients in the Department of Veterans Affairs. METHODS AND RESULTS: A cohort of 582 881 hypertensive patients and 260 924 normotensive individuals treated in 15 Department of Veterans Affairs medical centers between 2000 and 2010 were examined. Strategies used system-wide included blood pressure control as a performance measure, automatic notification to healthcare providers, electronic reminders, and a systematic revisit schedule. The main outcome measure was the percentage of hypertensive patients whose hypertension was controlled and the level of blood pressure each month. In the hypertensive cohort (mean age 62.9±13.4 years, 96.0% male), 52.3% of patients were white, 25.1% were black, and 21.1% were Hispanic. Blood pressure control rates improved from 45.7% in September 2000 to 76.3% in August 2010. Improvements were similar across ethnic, racial, age, and sex groups. Average systolic/diastolic blood pressure decreased from 142.6/77.1 mm Hg in 2000 to 131.2/74.8 mm Hg in 2010, a decrease of 11.3/2.3 mm Hg (P<0.0001 for both). Systolic and diastolic blood pressures were lower in summer than in winter, and this trend continued through 2010. On average, control rates increased by 3.0% per year and were 6.8% higher in summer than in winter. CONCLUSIONS: High rates of blood pressure control can be achieved in all age and ethnic groups and in both sexes.

Imaging modality for left ventricular ejection fraction estimation and effect of implantable cardioverter-defibrillator on mortality in patients with heart failure.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs count-based, respectively). OBJECTIVE: The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS: Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS: Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (P = .693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION: We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

OBJECTIVE: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis.

OBJECTIVE: Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS: We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. RESULTS: Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSION: Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Intrathoracic impedance preceding ventricular tachyarrhythmia episodes.

BACKGROUND: Heart failure is associated with ventricular tachyarrhythmias (VT/VF). Fluid accumulation during worsened heart failure may trigger VT/VF. Increased intrathoracic impedance has been correlated with fluid accumulation during heart failure. Implanted defibrillators capable of daily measures of intrathoracic impedance allow correlation of impedance with occurrence of VT/VF. We hypothesized that VT/VF episodes are preceded by decreases in intrathoracic impedance. The goal was to identify the relationship of intrathoracic impedance measured by implanted cardioverter defibrillators to the occurrence of VT/VF. METHOD: Implanted defibrillator follow-up data were obtained retrospectively. Those with Medtronic OptiVol (Medtronic Inc., Minneapolis, MN, USA), storing averaged daily and reference impedance values, were reviewed for VT/VF episodes. Impedance changes in the week leading up to VT/VF were analyzed. RESULTS: A total of 317 VT/VF episodes in a cohort of 121 patients' follow-up data were evaluated. Averaged daily intrathoracic impedance declined preceding 64% of VT/VF episodes, with an average decline of 0.46 +/- 0.35 Ohms from the day before the VT/VF episodes. However, the mean values of the averaged daily and reference impedance did not change significantly. A novel measure, DeltaTI, the sum of the daily differences between the averaged daily and reference impedance, was negative preceding 66% of VT/VF episodes (P < 0.001). The mean DeltaTI was -4.0 +/- 1.3 Ohms, which was significantly lower than the theoretically expected value of zero Ohms (P < 0.01). CONCLUSION: (1) Averaged daily impedance declined preceding 64% of VT/VF episodes, but the overall decline was of small magnitude; (2) a novel measure, DeltaTI, was negative preceding 66% of VT/VF episodes, and significantly below zero.

Management strategies when implanted cardioverter defibrillator leads fail: survey findings.

BACKGROUND: Defibrillator implanters have adopted different approaches to managing failures of multicomponent implanted cardioverter defibrillator (ICD) leads. Although recent publications identified single-component failures as common mechanisms of failure, there are no published data regarding how best to manage these failures. METHODS: An internet-based survey was conducted to identify current management strategies. Questions were asked regarding isolated failure of a high-voltage coil or of a pace/sense electrode, in order to identify the frequency of various techniques to correct these failures. RESULTS: A worldwide query collected strategies from 376 physicians identifying themselves as ICD-implanting physicians. Replies came from 28 countries, with the USA accounting for 83.2%. The survey was completed by 85.6% of respondents. Implant experience was >10 years for 61.1%, 3-10 years for 29.1%, and <3 years for 10.4%. When the right ventricular coil failed, 52% abandoned and 48% explanted the failed lead. In superior vena cava coil failure, 61.2% chose to simply exclude this coil, using the other intact lead components. For pace/sense defects, 53.1% chose to implant a new pace/sense lead or switch sensing electrodes, using the intact lead components. Medical literature (76.1%), personal experience (67.6%), and professional guidelines (63.7%) were strong decision-making influences. CONCLUSIONS: (1) Management decisions for single-component failures of ICD leads are complex; (2) Significant differences in management strategy exist among physicians; (3) Medical literature and professional guidelines are strong influences for these decisions; (4) A lead failure registry could help identify reasons for such differences and help guide management.

A graded association of exercise capacity and all-cause mortality in males with high-normal blood pressure.

INTRODUCTION: Information regarding the effect of exercise capacity on mortality risk in individuals with high-normal blood pressure is severely limited. Thus, we evaluated the association of exercise capacity and all-cause mortality in individuals with high-normal blood pressure. METHODS: Exercise test was performed in 1727 males with high-normal blood pressure at two Veteran sites (Washington, DC, and Palo Alto, CA). Fitness status was assessed in metabolic equivalents (METs) at exercise peak. All-cause mortality was recorded for a mean follow-up period of 9.8+/-6.0 years. RESULTS: Exercise capacity was inversely associated with all-cause mortality, and the association was independent of traditional cardiovascular risk factors. For each 1 MET increase in exercise capacity, the adjusted mortality risk was reduced by 13%, underscoring the strong predictive value of exercise capacity that was confirmed by ROC analysis. Data analysis according to fitness levels revealed a threshold level of 4 METs, over which the mortality risk was progressively reduced by 30% (hazard ratio=0.70; CI 0.51-0.95) for those who achieved 4.1-6.0 METs and 61% (hazard ratio=0.39; CI 0.26-0.57) for those who achieved 8.1-10 METs. No additional reductions in risk were noted until the MET level achieved exceeded 12 METs. CONCLUSIONS: We observed a strong, inverse, graded and independent association between exercise capacity and all-cause mortality in individuals with high-normal blood pressure. Our findings indicate that a shift of the fitness curve to the right is associated with significant survival benefits, and even slight differences in fitness levels are associated with substantial reductions in mortality risk.

Amiodarone versus sotalol for atrial fibrillation.

BACKGROUND: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring. RESULTS: Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups. CONCLUSIONS: Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

Association between lifetime risk of atrial fibrillation and mortality in the oldest old.

BACKGROUND: Age is the strongest predictor of atrial fibrillation (AF), yet little is known about AF incidence in the oldest old. HYPOTHESIS: AF incidence declines after age 90 years, and morbidity is compressed into a brief period at the end of life. METHODS: In this retrospective, longitudinal cohort study of patients (born 1905-1935), we examined cumulative lifetime incidence of AF and its impact on mortality. Data included records from 1 062 610 octogenarians, 317 161 nonagenarians, and 3572 centenarians. Kaplan-Meier curves were used to estimate cumulative incidence of AF by age group, incidence rates were compared using log-rank tests, and Cox proportional hazards model was used to estimate unadjusted hazard ratios. The primary outcome was AF incidence at age > 80 years; the secondary outcome was mortality. RESULTS: The cumulative AF incidence rate was 5.0% in octogenarians, 5.4% in nonagenarians, and 2.3% in centenarians. Octogenarians and nonagenarians had a higher risk of AF incidence compared to centenarians (adjusted hazard ratio 8.74, 95% confidence interval [CI]: 6.31-12.04; and 2.98, 95% CI: 2.17-4.1, respectively). The lowest hazard ratio for mortality in patients with AF compared to those without was 2.3 (95% CI: 2.3-2.4) in patients who were on antiplatelet and anticoagulant medication and had a score of 0 on the Elixhauser comorbidity index score. CONCLUSIONS: Although AF incidence increased with age, being a centenarian was associated with reduced incidence and compression of morbidity. Patients with AF had a higher adjusted mortality rate. However, data suggest that a regimen of anticoagulants and antiplatelets may reduce risk of mortality in patients over 80 with an AF diagnosis.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

AIMS: To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. METHODS AND RESULTS: Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). CONCLUSION: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

A Comprehensive Multimorbidity Index for Predicting Mortality in Intensive Care Unit Patients.

BACKGROUND: Accurate prediction of mortality for patients admitted to the intensive care units (ICUs) is an important component of medical care. However, little is known about the role of multimorbidity in predicting end of life for high-risk and vulnerable patients. OBJECTIVE: The aim of the study was to derive and validate a multimorbidity risk model in an attempt to predict all-cause mortality at 6 and 12 months posthospital discharge. METHODS: This is a retrospective, observational, clinical cohort study. Data were collected on 442,692 ICU patients who received care through the Veterans Administration between January 2003 and December 2013. The primary outcome was all-cause mortality at 6 and 12 months posthospital discharge. We divided the data into derivation (80%) and validation (20%) sets. Using multivariable logistic regression models, we compared prognostic models based on age, principal diagnosis groups, physiological markers, immunosuppressants, comorbidity categories, and a newly developed multimorbidity index (MMI) based on 5695 comorbidities. The cross-validated area under the receiver operating characteristic curve (AUC) was used to report the accuracy of predicting all-cause mortality at 6 and 12 months of hospital discharge. RESULTS: The average age of patients was 68.87 years (standard deviation = 12.1), 95.9% were males, 44.9% were widowed, divorced, or separated. The relative order of accuracy in predicting mortality was the MMI (AUC = 0.84, CI = 0.83-0.84), VA Inpatient Evaluation Center index (AUC = 0.80, CI = 0.79-0.81), principal diagnosis groups (AUC = 0.74, CI = 0.73-0.74), comorbidities (AUC = 0.69, CI = 0.68-0.70), physiological markers (AUC = 0.65, CI = 0.64-0.65), age (AUC = 0.60, CI = 0.60-0.61),and immunosuppressant use (AUC = 0.59, CI = 0.58-0.59). CONCLUSIONS: The MMI improved the accuracy of predicting short- and long-term all-cause mortality for ICU patients. Further prospective studies are needed to validate the index in different clinical settings and test generalizability of results in patients outside the VA system of care.

Systolic-diastolic hypertension versus isolated systolic hypertension and incident heart failure in older adults: Insights from the Cardiovascular Health Study.

BACKGROUND: Isolated systolic hypertension (ISH) is common in older adults and is a risk factor for incident heart failure (HF). We examined the association of systolic-diastolic hypertension (SDH) with incident HF and other outcomes in older adults. METHODS: In the Cardiovascular Health Study (CHS), 5776 community-dwelling adults≥65years had data on baseline systolic and diastolic blood pressure (SBP and DBP). We excluded those with DBP<60mmHg (n=821), DBP≥90 and SBP<140mmHg (n=28), normal BP, taking anti-hypertensive drugs (n=1138), normal BP, not taking anti-hypertensive drugs, history of hypertension (n=193), and baseline HF (n=101). Of the remaining 3495, 1838 had ISH (SBP≥140 and DBP<90mmHg) and 240 had SDH (SBP≥140 and DBP≥90mmHg). The main outcome was centrally-adjudicated incident HF over 13years of follow-up. RESULTS: Participants had a mean (±SD) age of 73 (±6)years, 57% were women, and 16% African American. Incident HF occurred in 25%, 22% and 11% of participants with ISH, SDH and no hypertension, respectively. Compared to no hypertension, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident HF associated with ISH and SDH were 1.86 (1.51-2.30) and 1.73 (1.23-2.42), respectively. Cardiovascular mortality occurred in 22%, 24% and 9% of those with ISH, SDH and no hypertension, respectively with respective multivariable-adjusted HRs (95% CIs) of 1.88 (1.49-2.37) and 2.30 (1.64-3.24). CONCLUSION: Among older adults with hypertension, both SDH and ISH have similar associations with incident HF and cardiovascular mortality.

Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized for Heart Failure.

BACKGROUND: Digoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). In the current study, we examined this association among long-term care (LTC) residents hospitalized for HF. METHODS: Of the 8049 Medicare beneficiaries discharged alive after hospitalization for HF from 106 Alabama hospitals, 545 (7%) were LTC residents, of which 227 (42%) received discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 545 patients, were used to assemble a matched cohort of 158 pairs of patients receiving and not receiving digoxin who were balanced on 29 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin among matched patients were estimated using Cox regression models. RESULTS: Matched patients (n = 316) had a mean age of 83 years, 74% were women, and 18% African American. Thirty-day all-cause readmission occurred in 21% and 20% of patients receiving and not receiving digoxin, respectively (HR, 1.02; 95% CI, 0.63-1.66). Digoxin had no association with all-cause mortality (HR, 0.90; 95% CI, 0.48-1.70), HF readmission (HR, 0.90; 95% CI, 0.38-2.12), or a combined endpoint of all-cause readmission or all-cause mortality (HR, 0.97; 95% CI, 0.65-1.45) at 30 days. These associations remained unchanged at 1 year postdischarge. CONCLUSIONS: The lack of an association between digoxin and 30-day all-cause readmission in older nursing home residents hospitalized for HF is intriguing and needs to be interpreted with caution given the small sample size.

Higher risk for incident heart failure and cardiovascular mortality among community-dwelling octogenarians without pneumococcal vaccination.

AIMS: Octogenarians have the highest incidence of heart failure (HF) that is not fully explained by traditional risk factors. We explored whether lack of pneumococcal vaccination is associated with higher risk of incident HF among octogenarians. METHODS AND RESULTS: In the Cardiovascular Health Study (CHS), 5290 community-dwelling adults, ≥65 years of age, were free of baseline HF and had data on pneumococcal vaccination. Of these, 851 were octogenarians, of whom, 593 did not receive pneumococcal vaccination. Multivariable-adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for associations of lack of pneumococcal vaccination with incident HF and other outcomes during 13 years of follow-up were estimated using Cox regression models, adjusting for demographics and other HF risk factors including influenza vaccination. Octogenarians had a mean (±SD) age of 83 (±3) years; 52% were women and 17% African American. Overall, 258 participants developed HF and 662 died. Lack of pneumococcal vaccination was associated with higher relative risk of incident HF (aHR, 1.37; 95% CI, 1.01-1.85; P = 0.044). There was also higher risk for all-cause mortality (aHR, 1.23; 95% CI, 1.02-1.49; P = 0.028), which was mostly driven by cardiovascular mortality (aHR, 1.45; 95% CI, 1.06-1.98; P = 0.019). Octogenarians without pneumococcal vaccination had a trend toward higher risk of hospitalization due to pneumonia (aHR, 1.34; 95% CI, 0.99-1.81; P = 0.059). These associations were not observed among those 65-79 years of age. CONCLUSIONS: Among community-dwelling octogenarians, lack of pneumococcal vaccination was associated with a significantly higher independent risk of incident HF and mortality, and trend for higher pneumonia hospitalization.

Renin-Angiotensin System Inhibition and Lower 30-Day All-Cause Readmission in Medicare Beneficiaries with Heart Failure.

BACKGROUND: Heart failure is the leading cause for 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act. There is a growing interest in understanding the impact of evidence-based heart failure therapy on 30-day all-cause readmission. In the current study, we examined the impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI-ARBs) on 30-day all-cause readmission in heart failure. METHODS: Of the 1384 hospitalized Medicare beneficiaries with heart failure and left ventricular ejection fraction <45% discharged alive from 106 Alabama hospitals (1998-2001) without prior ACEI-ARB use and without known contraindications to ACEI-ARB use; 734 received new predischarge prescriptions for these drugs. Using propensity scores for ACEI-ARB initiation, we assembled a matched cohort of 477 pairs of patients balanced on 32 baseline characteristics (mean age 75 years, 46% women, 26% African American). RESULTS: Thirty-day all-cause readmissions occurred in 18% and 24% of matched patients receiving and not receiving ACEI-ARBs, respectively (hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.56-0.97; P = .030). ACEI-ARB use was also associated with lower risk of 30-day all-cause mortality (HR 0.56; 95% CI, 0.33-0.98; P = .041) and of the combined endpoint of 30-day all-cause readmission or 30-day all-cause mortality (HR 0.73; 95% CI, 0.56-0.94; P = .017). All associations remained significant at 1 year post discharge. CONCLUSIONS: Among hospitalized patients with heart failure and reduced ejection fraction, the use of ACEI-ARBs was associated with a significantly lower risk of 30-day all-cause readmission and 30-day all-cause mortality; both beneficial associations persisted during long-term follow-up.

Association of 30-Day All-Cause Readmission with Long-Term Outcomes in Hospitalized Older Medicare Beneficiaries with Heart Failure.

BACKGROUND: Heart failure is the leading cause for 30-day all-cause readmission. We examined the impact of 30-day all-cause readmission on long-term outcomes and cost in a propensity score-matched study of hospitalized patients with heart failure. METHODS: Of the 7578 Medicare beneficiaries discharged with a primary diagnosis of heart failure from 106 Alabama hospitals (1998-2001) and alive at 30 days after discharge, 1519 had a 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without a 30-day all-cause readmission, balanced on 34 baseline characteristics (mean age 75 years, 56% women, 24% African American). RESULTS: During 2-12 months of follow-up after discharge from index hospitalization, all-cause mortality occurred in 41% and 27% of matched patients with and without a 30-day all-cause readmission, respectively (hazard ratio 1.68; 95% confidence interval 1.48-1.90; P <.001). This harmful association of 30-day all-cause readmission with mortality persisted during an average follow-up of 3.1 (maximum, 8.7) years (hazard ratio 1.33; 95% confidence interval 1.22-1.45; P <.001). Patients with a 30-day all-cause readmission had higher cumulative all-cause readmission (mean, 6.9 vs 5.1; P <.001), a longer cumulative length of stay (mean, 51 vs 43 days; P <.001), and a higher cumulative cost (mean, $38,972 vs $34,025; P = .001) during 8.7 years of follow-up. CONCLUSIONS: Among Medicare beneficiaries hospitalized for heart failure, 30-day all-cause readmission was associated with a higher risk of subsequent all-cause mortality, higher number of cumulative all-cause readmission, longer cumulative length of stay, and higher cumulative cost.

Analysis of T-wave morphology from the 12-lead electrocardiogram for prediction of long-term prognosis in male US veterans.

BACKGROUND: The aim of the present study was to assess the prognostic value of novel repolarization descriptors from the 12-lead ECG in a large cohort of US veterans. METHODS AND RESULTS: Male US veterans (n=813) with cardiovascular disease had digital 12-lead ECGs recorded at the VA Medical Center, Washington, DC, between 1984 and 1991. The patient series was retrospectively compiled in 1991; follow-up was prospectively assessed until 2000. Novel ECG variables characterizing repolarization and the T-wave loop were automatically analyzed. Of 772 patients with technically analyzable data, 252 patients (32.6%) died after a mean follow-up of 10.4 +/- 3.8 years. Direct comparison between dead and alive patients showed that the so-called T-wave residua (the absolute and relative amount of nondipolar contents within the T wave) predicted mortality (111 900 +/- 164 700 versus 85 600 +/- 144 800 between dead and alive patients, P<0.0002; and 0.43 +/- 0.62% versus 0.33 +/- 0.56%, P<0.0005 for the absolute and relative T-wave residuum, respectively). On Cox regression analysis entering age, left ventricular ejection fraction, echocardiographic left ventricular hypertrophy, and either of the T-wave residua, risk prediction was independent for the absolute (P=0.022) and for the relative (P=0.006) T-wave residuum, respectively, with age (P<0.0001), presence of left ventricular hypertrophy (P=0.002), and left ventricular ejection fraction (P=0.004) also being predictors of survival. CONCLUSIONS: The heterogeneity of myocardial repolarization, measured by the so-called T-wave residuum in the ECG, confers long-term independent prognostic information in US veterans with cardiovascular disease.

Causal Analysis of Emergency Department Delays.

BACKGROUND: Improvement teams make causal inferences, but the methods they use are based on statistical associations. This article shows how data and statistical models can be used to help improvement teams make causal inferences and find the root causes of problems. METHODS: This article uses attribution data, competing risk survival analysis, and Bayesian network probabilities to analyze excessive emergency department (ED) stays within one hospital. We use data recorded by ED clinicians that attributed the cause of excessive ED stays to 23 causes for the 70 049 ED visits between March 2011 and April 2014. We use competing risk survival analysis to identify contribution of each cause to the delay. We use Bayesian network models to analyze interaction among different causes of excessive stays and find the root causes of this problem. RESULTS: This article shows the utility of causal analysis to help improvement teams focus on the root causes of problems. For the example analyzed in the article, most causes for patients' excessive ED stays were related to the hospital operations outside the ED. Therefore, improvement projects inside the ED such as expanding ED, increasing staff at the ED, or improving operations are less likely to have a positive impact on reducing excessive ED stays. On the contrary, interventions that improve hospital occupancy (better discharge, expansion of beds, etc) or improve laboratory response times are more likely to result in positive outcomes.

Relationship of Physical Activity and Healthy Eating with Mortality and Incident Heart Failure among Community-Dwelling Older Adults with Normal Body Mass Index.

AIMS: Normal body mass index (BMI) is associated with lower mortality and may be achieved by physical activity (PA), healthy eating (HE), or both. We examined the association of PA and HE with mortality and incident heart failure (HF) among 2040 community-dwelling older adults aged ≥ 65 years with baseline BMI 18.5 to 24.99 kg/m2 during 13 years of follow-up in Cardiovascular Health Study. METHODS AND RESULTS: Baseline PA was defined as ≥500 weekly metabolic equivalent task-minutes (MET-minutes) and HE as ≥5 daily servings of vegetable and fruit intake. Participants were categorized into 4 groups: (1) PA-/HE- (n=384); (2) PA+/HE- (n=992); (3) PA-/HE+ (n=162); and (4) PA+/HE+ (n=502). Participants had a mean age of 74 (±6) years, mean BMI of 22.6 (±1.5) kg/m2, 61% were women, and 4% African American. Compared with PA-/HE-, age-sex-race-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality for PA-/HE+, PA+/HE-, and PA+/HE+ groups were 0.96 (0.76-1.21), 0.61 (0.52-0.71) and 0.62 (0.52-0.75), respectively. These associations remained unchanged after multivariable adjustment and were similar for cardiovascular and non-cardiovascular mortalities. Respective demographic-adjusted HRs (95% Cis) for incident HF among 1954 participants without baseline HF were 1.21 (0.81-1.81), 0.71 (0.54-0.94) and 0.71 (0.51-0.98). These later associations lost significance after multivariable-adjustment. CONCLUSION: Among community-dwelling older adults with normal BMI, physical activity, regardless of healthy eating, was associated with lower risk of mortality and incident HF, but healthy eating had no similar protective association in this cohort.

SCD-HeFT: Use of R-R interval statistics for long-term risk stratification for arrhythmic sudden cardiac death.

BACKGROUND: In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), a significant fraction of the patients with congestive heart failure ultimately did not die suddenly of arrhythmic causes. Patients with CHF will benefit from better tools to identify if implantable cardioverter-defibrillator (ICD) therapy is needed. OBJECTIVES: We aimed to identify predictor variables from baseline SCD-HeFT patients' R-R intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test. METHODS: Ten predictor variables were extracted from prerandomization Holter data from 475 patients enrolled in the ICD arm of the SCD-HeFT by using novel and traditional heart rate variability methods. All variables were correlated to SCD using the Mann-Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed. RESULTS: A short-term fractal exponent, α1, and a long-term fractal exponent, α2, from detrended fluctuation analysis, the ratio of low- to high-frequency power, the number of premature ventricular contractions per hour, and the heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (P < .001) and survival (log-rank, P < .01). The most powerful multivariate predictor tool using the Cox proportional hazards regression model was α2 with a hazard ratio of 0.0465 (95% confidence interval 0.00528-0.409; P < .01). CONCLUSION: Predictor variables extracted from R-R intervals correlate to the occurrences of SCD and distinguish survival functions among patients with ICDs in SCD-HeFT. We believe that SCD prediction models should incorporate Holter-based R-R interval analysis to refine ICD patient selection, especially to exclude patients who are unlikely to benefit from ICD therapy.