Estimated Glomerular Filtration Rate Variability in Patients With Heart Failure and Chronic Kidney Disease.

BACKGROUND: Greater variability in the estimated glomerular filtration rate (eGFR) is associated with higher mortality in patients with chronic kidney disease (CKD). Heart failure (HF) is common in CKD and may increase variability through changes in hemodynamic and volume regulation. We sought to determine if patients with vs without HF have higher kidney function variability in CKD, and to define the association with mortality. METHODS AND RESULTS: Patients undergoing coronary angiography from 2003 to 2013 with an eGFR of less than 60 mL/min/1.73 m2 were evaluated from the Duke Databank for Cardiovascular Disease. Variability in the eGFR, measured as the coefficient of variation (CV) of residuals from the regression of eGFR vs time, was calculated spanning 3 months to 2 years after catheterization. Mortality was assessed 2 to 7 years after catheterization. Patients were grouped into 3 HF phenotypes: HF with reduced ejection fraction, HF with preserved ejection, and no HF. Regression was used to evaluate associations between HF phenotypes and variability in the eGFR and between variability in the eGFR and mortality rate with stratification by HF phenotype. Among 3767 participants, the median eGFR at baseline was 45 mL/min/1.73 m2 (interquartile range 33-53 mL/min/1.73 m2), and longitudinal measures of eGFR over 21 months had within-patient residual variability (CV) of 14% (9%-20%). In adjusted analyses, variability in the eGFR was greater in those with HF with preserved ejection (n = 695, CV difference 0.98%, 95% confidence interval 0.14%-1.81%) or HF with reduced ejection fraction (n = 800, CV difference 2.51%, 95% confidence interval 1.66%-3.37%) relative to no HF (n = 2272). In 3068 participants eligible for mortality analysis, the presence of HF and greater variability in the eGFR were each associated independently with higher mortality, but there was no evidence of interaction between variability in the eGFR and any HF phenotype (all P for interaction ≥.49). CONCLUSIONS: Variability in the eGFR is greater in patients with HF and associated with mortality. Prediction algorithms and classification schemes should consider not only static, but also dynamic eGFR variability in HF and CKD prognostication.

Pulmonary Hypertension Subtypes and Mortality in CKD.

RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) contributes to cardiovascular disease and mortality in patients with chronic kidney disease (CKD), but the pathophysiology is mostly unknown. This study sought to estimate the prevalence and consequences of PH subtypes in the setting of CKD. STUDY DESIGN: Observational retrospective cohort study. SETTING & PARTICIPANTS: We examined 12,618 patients with a right heart catheterization in the Duke Databank for Cardiovascular Disease from January 1, 2000, to December 31, 2014. EXPOSURES: Baseline kidney function stratified by CKD glomerular filtration rate category and PH subtype. OUTCOMES: All-cause mortality. ANALYTICAL APPROACH: Multivariable Cox proportional hazards analysis. RESULTS: In this cohort, 73.4% of patients with CKD had PH, compared with 56.9% of patients without CKD. Isolated postcapillary PH (39.0%) and combined pre- and postcapillary PH (38.3%) were the most common PH subtypes in CKD. Conversely, precapillary PH was the most common subtype in the non-CKD cohort (35.9%). The relationships between mean pulmonary artery pressure, pulmonary capillary wedge pressure, and right atrial pressure with mortality were similar in both the CKD and non-CKD cohorts. Compared with those without PH, precapillary PH conferred the highest mortality risk among patients without CKD (HR, 2.27; 95% CI, 2.00-2.57). By contrast, in those with CKD, combined pre- and postcapillary PH was associated with the highest risk for mortality in CKD in adjusted analyses (compared with no PH, HRs of 1.89 [95% CI, 1.57-2.28], 1.87 [95% CI, 1.52-2.31], 2.13 [95% CI, 1.52-2.97], and 1.63 [95% CI, 1.12-2.36] for glomerular filtration rate categories G3a, G3b, G4, and G5/G5D). LIMITATIONS: The cohort referred for right heart catheterization may not be generalizable to the general population. Serum creatinine data in the 6 months preceding catheterization may not reflect true baseline CKD. Observational design precludes assumptions of causality. CONCLUSIONS: In patients with CKD referred for right heart catheterization, PH is common and associated with poor survival. Combined pre- and postcapillary PH was common and portended the worst survival for patients with CKD.

The prognostic value of diastolic and systolic mechanical left ventricular dyssynchrony among patients with coronary artery disease and heart failure.

BACKGROUND: Prevalence and prognostic value of diastolic and systolic dyssynchrony in patients with coronary artery disease (CAD) + heart failure (HF) or CAD alone are not well understood. METHODS: We included patients with gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) between 2003 and 2009. Patients had at least one major epicardial obstruction ≥ 50%. We assessed the association between dyssynchrony and outcomes, including all-cause and cardiovascular death. RESULTS: Of the 1294 patients, HF was present in 25%. Median follow-up was 6.7 years (IQR 4.9-9.3) years with 537 recorded deaths. Patients with CAD + HF had a higher incidence of dyssynchrony than patients with CAD alone (diastolic BW 28.8% for the HF + CAD vs 14.7% for the CAD alone). Patients with CAD + HF had a lower survival than CAD alone at 10 years (33%; 95% CI 27-40 vs 59; 95% CI 55-62, P < 0.0001). With one exception, HF was found to have no statistically significant interaction with dyssynchrony measures in unadjusted and adjusted survival models. CONCLUSIONS: Patients with CAD + HF have a high prevalence of mechanical dyssynchrony as measured by GSPECT MPI, and a higher mortality than CAD alone. However, clinical outcomes associated with mechanical dyssynchrony did not differ in patients with and without HF.

Racial differences in long-term outcomes among black and white patients with drug-eluting stents.

BACKGROUND: Some studies suggest that black patients may have worse outcomes after drug-eluting stent (DES) placement. There are limited data characterizing long-term outcomes by race. The objective was to compare long-term outcomes between black and white patients after percutaneous coronary intervention (PCI) with DES implantation. METHODS: We analyzed 915 black and 3,559 white (n = 4,474) consecutive patients who underwent DES placement at Duke University Medical Center from 2005 through 2013. Over 6-year follow up, we compared rates of myocardial infarction (MI), all-cause mortality, revascularization, and major bleeding between black and white patients. A multivariable Cox regression model was fit to adjust for potentially confounding variables. Dual-antiplatelet therapy use over time was determined by patient follow-up surveys and compared by race. RESULTS: Black patients were younger; were more often female; had higher body mass indexes; had more diabetes mellitus, hypertension, and renal disease; and had lower median household incomes than white patients (P < .001). At 6 years after DES placement, black relative to white patients had higher unadjusted rates of MI (12.1% vs 10.1%, hazard ratio 1.25, 95% CI 1.00-1.57, P = .05) and major bleeding (17.8% vs 14.3%, hazard ratio 1.28, 95% CI 1.07-1.54, P = .01), but there were no significant differences in other outcomes. After multivariable adjustment, there were no statistically significant racial differences in any of these outcomes at 6 years. Similarly, dual-antiplatelet therapy use was comparable between racial groups. CONCLUSIONS: Unadjusted rates of MI and major bleeding over long-term follow up were higher among black patients compared to white patients, but these differences may be explained by racial differences in comorbid disease.

Trends in cardiorespiratory fitness: The evolution of exercise treadmill testing at a single Academic Medical Center from 1970 to 2012.

OBJECTIVE: To identify temporal trends in the use of exercise treadmill testing (ETT) and cardiorespiratory fitness (CRF) estimated by ETT in metabolic equivalents (METs). PATIENTS AND METHODS: We compiled an ETT database of all available treadmill tests-including those with concomitant stress echocardiography and nuclear perfusion imaging studies-performed at Duke University Hospital from January 1, 1970- December 31, 2012. Six different ramp protocols were used in these combined modalities. CRF at maximal exertion was estimated using established metrics. Eligible patients were required to have no missing data on maximal treadmill speed, grade, and protocol. RESULTS: The most commonly used ETT protocol was the Bruce (n = 28,877), followed by manual test (n = 7390). Since the 1980's, the use of ETT for clinical purposes declined substantially; there was a decreased trend in utilization of 9.4% over the decades 1990-1999 and 2000-2009. When standard protocol (Bruce) was assessed in isolation, trends in CRF decreased progressively from 1970 to 2012 (mean METs (standard deviation): 11.7 (4.3) to 10.5 (3.5)). After adjusting for baseline comorbidities, the trend was reduced to a lesser degree. CONCLUSIONS: The use of ETT at our institution has declined over time, perhaps due to changes in clinical practice. In patients undergoing ETT using the standard Bruce protocol, CRF decreased progressively over the last five decades. Future studies are needed to clarify the etiology of the decrease in use of such a powerful predictor of clinical outcomes in our medical care environment.

Long-term outcomes of mitral regurgitation by type and severity.

BACKGROUND: We aimed to determine the association of MR severity and type with all-cause death in a large, real-world, clinical setting. METHODS: We reviewed full echocardiography studies at Duke Echocardiography Laboratory (01/01/1995-12/31/2010), classifying MR based on valve morphology, presence of coronary artery disease, and left ventricular size and function. Survival was compared among patients stratified by MR type and baseline severity. RESULTS: Of 93,007 qualifying patients, 32,137 (34.6%) had ≥mild MR. A total of 8094 (8.7%) had moderate/severe MR, which was primary myxomatous (14.1%), primary non-myxomatous (6.2%), secondary non-ischemic (17.0%), and secondary ischemic (49.4%). At 10 years, patients with primary myxomatous MR or MR due to indeterminate cause had survival rates of >60%; primary non-myxomatous, secondary ischemic, and non-ischemic MR had survival rates <50%. While mild (HR 1.06, 95% CI 1.03-1.09), moderate (HR 1.31, 95% CI 1.27-1.37), and severe (HR 1.55, 95% CI 1.46-1.65) MR were independently associated with all-cause death, the relationship of increasing MR severity with mortality varied across MR types (P ≤ .001 for interaction); the highest risk associated with worsening severity was seen in primary myxomatous MR followed by secondary ischemic MR and primary non-myxomatous MR. CONCLUSIONS: Although MR severity is independently associated with increased all-cause death risk for most forms of MR, the absolute mortality rates associated with worse MR severity are much higher for primary myxomatous, non-myxomatous, and secondary ischemic MR. The findings from this study support carefully defining MR by type and severity.

The relationship between baseline and follow-up left ventricular ejection fraction with adverse events among primary prevention ICD patients.

BACKGROUND: Left ventricular ejection fraction (LVEF) is used to select patients for primary prevention implantable cardioverter defibrillators (ICDs). The relationship between baseline and long-term follow-up LVEF and clinical outcomes among primary prevention ICD patients remains unclear. METHODS: We studied 195 patients with a baseline LVEF ≤35% ≤6 months prior to ICD implantation and follow-up LVEF 1-3 years after ICD implantation without intervening left ventricular assist device (LVAD) or transplant. The co-primary study endpoints were: (1) a composite of time to death, LVAD, or transplant and (2) appropriate ICD therapy. We examined multivariable Cox proportional hazard models with a 3-year post-implant landmark view; the LVEF closest to the 3-year mark was considered the follow-up LVEF for analyses. Follow-up LVEF was examined using 2 definitions: (1) ≥10% improvement compared to baseline or (2) actual value of ≥40%. RESULTS: Fifty patients (26%) had a LVEF improvement of ≥10% and 44 (23%) had a follow-up LVEF ≥40%. Neither baseline nor follow-up LVEF was significantly associated with the composite endpoint. In contrast, both baseline and follow-up LVEF were associated with risk for long-term ICD therapies, whether follow-up LVEF was modeled as a ≥10% absolute improvement (baseline LVEF HR 0.87, CI 0.91-0.93, P < .001; follow-up LVEF HR 0.18, CI 0.06-0.53, P = .002) or a ≥40% follow-up value (baseline LVEF HR 0.89, CI 0.83-0.96, P = .001, follow-up LVEF HR 0.26, CI 0.08-0.87, P = .03). CONCLUSIONS: Among primary prevention ICD recipients, both baseline and follow-up LVEF were independently associated with long-term risk for appropriate ICD therapy, but they were not associated with time to the composite of LVAD, transplant, or death.

Predicting risk of cardiac events among ST-segment elevation myocardial infarction patients with conservatively managed non-infarct-related artery coronary artery disease: An analysis of the Duke Databank for Cardiovascular Disease.

BACKGROUND: Recent randomized evidence has demonstrated benefit with complete revascularization during the index hospitalization for multivessel coronary artery disease ST-segment elevation myocardial infarction (STEMI) patients; however, this benefit likely depends on the risk of future major adverse cardiovascular events (MACE). METHODS: Using data from Duke University Medical Center (2003-2012), we identified those at high risk for 1-year MACE among 664 STEMI patients with conservatively managed non-infarct-related artery (non-IRA) lesions. Using multivariable logistic regression, we identified clinical and angiographic characteristics associated with MACE (death, myocardial infarction, urgent revascularization) to 1 year and developed an integer-based risk prediction model for clinical use. RESULTS: In this cohort (median age 60 years, 30% female), the unadjusted Kaplan-Meier rates for MACE at 30 days and 1 year were 10% and 28%, respectively. Characteristics associated with MACE at 1 year included reduced left ventricular ejection fraction, hypertension, heart failure, higher-risk non-IRA vessels (left main), renal insufficiency, and greater % stenosis of non-IRA lesions. A 15-point risk score including these variables had modest discrimination (C-index 0.67) across a spectrum of subsequent risk (4%-88%) for 1-year MACE. CONCLUSIONS: There is a wide spectrum of risk following primary percutaneous coronary intervention for STEMI patients with multivessel disease. Using readily available clinical characteristics, the expected incidence of MACE by 1 year can be calculated with a simplified risk score, facilitating a tailored approach to clinical care.

The prognostic value of mechanical left ventricular dyssynchrony defined by phase analysis from gated single-photon emission computed tomography myocardial perfusion imaging among patients with coronary heart disease.

BACKGROUND: The prognostic value of left ventricular dyssynchrony measured by gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) and its relationship to electrical dyssynchrony measured by QRS duration are incompletely understood. The aim of this study was therefore to examine the independent and incremental prognostic value of dyssynchrony in yet the largest group of patients with coronary artery disease (CAD). METHODS AND RESULTS: Patients presenting for GSPECT- MPI between July 1993 and May 1999 in normal sinus rhythm were identified from the Duke Nuclear Cardiology Databank and the Duke Databank for Cardiovascular Disease (N = 1244). After a median of 4.2 years, 336 deaths occurred. At 8 years, the Kaplan-Meier estimates of the probability of death were 34.0% among patients with a phase bandwidth <100° and 56.8% among those with a bandwidth ≥100°. After adjustment for standard clinical variables, QRS dyssynchrony was independently associated with death (Hazard Ratio (HR), per 10°: 1.092, 95% Confidence Interval (CI) 1.048,1.139, P < .0001). Phase bandwidth was similarly associated with death after clinical adjustment (HR per 10°: 1.056, 95% CI 1.041,1.072, P < .0001). In clinically adjusted models examining QRS duration in addition to phase bandwidth, phase bandwidth had a stronger association with mortality. After accounting for left ventricular ejection fraction (LVEF), neither QRS duration nor phase bandwidth were statistically significant. Among patients with EF >35%, QRS duration and phase bandwidth together provided value above that provided by LVEF alone (P = 0.0181). When examining cardiovascular death, results were consistent with all-cause death. CONCLUSIONS: Among patients with CAD, mechanical left ventricular dyssynchrony measured by GSPECT MPI has a stronger relationship with outcomes than electrical dyssynchrony measured by QRS duration. After adjustment for baseline characteristics and LVEF, neither mechanical nor electrical dyssynchrony is independently associated with all-cause death or cardiac death. Among patients with EF >35%, mechanical and electrical dyssynchrony together provided prognostic value above that afforded by LVEF.

Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction.

AIMS: We aimed to determine the frequency of aortic valve surgery (AVR) with or without coronary artery bypass grafting (CABG), among patients with moderate/severe aortic stenosis (AS) and left ventricular systolic dysfunction (LVSD), and its relationship with survival. METHODS AND RESULTS: The Duke Echocardiographic Database (N = 132 804) was queried for patients with mean gradient ≥25 mmHg and/or peak velocity ≥3 m/s and LVSD (left ventricular ejection fraction ≤50%) from 1 January 1995-28 February 2014. For analyses purposes, AS was defined both by mean gradient and calculated aortic valve area (AVA) criteria. Time-dependent indicators of AVR in multivariable Cox models were used to assess the relationship of AVR and all-cause mortality. A total of 1634 patients had moderate (N = 1090, 67%) or severe (N = 544, 33%) AS by mean gradient criteria. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. There were 863 (53%) deaths observed up to 5 years following index echo. After multivariable adjustment in an inverse probability weighted regression model, AVR was associated with higher 5-year survival amongst patients with moderate AS and severe AS whether classified by AVA or mean gradient criteria. Over all, AVR ± CABG compared with medical therapy was associated with significantly lower mortality [hazard ratio, HR = 0.49 (0.38, 0.62), P < 0.0001]. Compared with CABG alone, CABG + AVR was associated with better survival [HR = 0.18 (0.12, 0.27), P < 0.0001]. CONCLUSIONS: In patients with moderate/severe AS and LVSD, mortality is substantial and amongst those selected for surgery, AVR with or without CABG is associated with higher survival. Research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

Prognostic value of the cadmium-zinc-telluride camera: A comparison with a conventional (Anger) camera.

BACKGROUND: New multipinhole cadmium-zinc-telluride (CZT) cameras allow for faster imaging and lower radiation doses for single photon emission computed tomography (SPECT) studies, but assessment of prognostic ability is necessary. METHODS AND RESULTS: We collected data from all myocardial SPECT perfusion studies performed over 15 months at our institution, using either a CZT or conventional Anger camera. A Cox proportional hazards model was used to assess the relationship between camera type, imaging results, and either death or myocardial infarction (MI). Clinical variables including age, sex, body mass index (BMI), and historical risk factors were used for population description and model adjustments. We had 2,088 patients with a total of 69 deaths and 65 MIs (122 events altogether). A 3% increase in DDB (difference defect burden) represented a 12% increase in the risk of death or MI, whereas a 3% increase in rest defect burden or stress defect burden represented an 8% increase; these risks were the same for both cameras (P > .24, interaction tests). CONCLUSIONS: The CZT camera has similar prognostic values for death and MI to conventional Anger cameras. This suggests that it may successfully be used to decrease patient dose.

Clinical predictors and outcomes of patients with left ventricular thrombus following ST-segment elevation myocardial infarction.

We aimed to characterize the independent predictors of LVT following STEMI and the association with outcomes. The clinical predictors of left ventricular thrombus (LVT) formation after ST-segment elevation myocardial infarction (STEMI) are not well-defined in the contemporary era. We performed a retrospective analysis of STEMI patients at Duke from 2000 to 2011 who had a transthoracic echocardiogram within 90 days post-STEMI and compared patients with and without LVT (LVT+ vs. LVT-). Univariate Cox proportional hazards regression models of baseline characteristics were examined and significant variables were used in a multivariable model to assess adjusted relationships with LVT. A multivariable Cox PH survival model with covariate adjustments was used for assessment of LVT and long-term mortality. Of all eligible patients, 1734 patients met inclusion criteria and 4.3 % (N = 74) had a LVT. LVT+ patients tended to have a history of heart failure (HF) and higher initial troponin compared to LVT- patients. After adjustment, higher heart rate, non-white race, HF severity, and presence of left anterior descending artery (LAD) disease were independent predictors of LVT. There was a trend toward an association between LVT and increased all-cause mortality (HR 1.36; 95 % CI 0.84-2.21, P = 0.22), however this was not statistically significant. LVT was seen in over 4 % of this contemporary post-STEMI population. Several baseline characteristics were independently associated with LVT: Heart rate, HF severity, LAD disease, and non-white race. Prospective studies are warranted to determine whether anticoagulation in patients at increased risk for LVT improves outcomes.

Management and outcomes in patients with moderate or severe functional mitral regurgitation and severe left ventricular dysfunction.

AIMS: The management and outcomes of patients with functional moderate/severe mitral regurgitation and severe left ventricular (LV) systolic dysfunction are not well defined. We sought to determine the characteristics, management strategies, and outcomes of patients with moderate or severe mitral regurgitation (MR) and LV systolic dysfunction. METHODS AND RESULTS: For the period 1995-2010, the Duke Echocardiography Laboratory and Duke Databank for Cardiovascular Diseases databases were merged to identify patients with moderate or severe functional MR and severe LV dysfunction (defined as LV ejection fraction ≤ 30% or LV end-systolic diameter > 55 mm). We examined treatment effects in two ways. (i) A multivariable Cox proportional hazards model was used to assess the independent relationship of different treatment strategies and long-term event (death, LV assist device, or transplant)-free survival among those with and without coronary artery disease (CAD). (ii) To examine the association of mitral valve (MV) surgery with outcomes, we divided the entire cohort into two groups, those who underwent MV surgery and those who did not; we used inverse probability weighted (IPW) propensity adjustment to account for non-random treatment assignment. Among 1441 patients with moderate (70%) or severe (30%) MR, a significant history of hypertension (59%), diabetes (28%), symptomatic heart failure (83%), and CAD (52%) was observed. Past revascularization in 26% was noted. At 1 year, 1094 (75%) patients were treated medically. Percutaneous coronary intervention was performed in 114 patients, coronary artery bypass graft (CABG) surgery in 82, CABG and MV surgery in 96, and MV surgery alone in 55 patients. Among patients with CAD, compared with medical therapy alone, the treatment strategies of CABG surgery [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.42-0.76] and CABG with MV surgery (HR 0.58, 95% CI 0.44-0.78) were associated with long-term, event-free survival benefit. Percutaneous intervention treatment produced a borderline result (HR 0.78, 95% CI 0.61-1.00). However, the relationship with isolated MV surgery did not achieve statistical significance (HR 0.64, 95% CI 0.33-1.27, P = 0.202). Among those with CAD, following IPW adjustment, MV surgery was associated with a significant event-free survival benefit compared with patients without MV surgery (HR 0.71, 95% CI 0.52-0.95). In the entire cohort, following IPW adjustment, the use of MV surgery was associated with higher event-free survival (HR 0.69, 95% CI 0.53-0.88). CONCLUSION: In patients with moderate or severe MR and severe LV dysfunction, mortality was substantial, and among those selected for surgery, MV surgery, though performed in a small number of patients, was independently associated with higher event-free survival.

Surgical revascularization is associated with maximal survival in patients with ischemic mitral regurgitation: a 20-year experience.

BACKGROUND: The optimal treatment for ischemic mitral regurgitation remains actively debated. Our objective was to evaluate the relationship between ischemic mitral regurgitation treatment strategy and survival. METHODS AND RESULTS: We retrospectively reviewed patients at our institution diagnosed with significant coronary artery disease and moderate or severe ischemic mitral regurgitation from 1990 to 2009, categorized by medical treatment alone, percutaneous coronary intervention, coronary artery bypass grafting (CABG), or CABG plus mitral valve repair or replacement. Kaplan-Meier methods and multivariable Cox proportional hazards analyses were performed to assess the relationship between treatment strategy and survival, with the use of propensity scores to account for nonrandom treatment assignment. A total of 4989 patients were included: medical treatment alone=36%, percutaneous coronary intervention=26%, CABG=33%, and CABG plus mitral valve repair or replacement=5%. Median follow-up was 5.37 years. Compared with medical treatment alone, significantly lower mortality was observed in patients treated with percutaneous coronary intervention (adjusted hazard ratio, 0.83; 95% confidence interval, 0.76-0.92; P=0.0002), CABG (adjusted hazard ratio, 0.56; 95% confidence interval, 0.51-0.62; P<0.0001), and CABG plus mitral valve repair or replacement (adjusted hazard ratio, 0.69; 95% confidence interval, 0.57-0.82; P<0.0001). There was no significant difference in these results based on mitral regurgitation severity. CONCLUSIONS: Patients with significant coronary artery disease and moderate or severe ischemic mitral regurgitation undergoing CABG alone demonstrated the lowest risk of death. CABG with or without mitral valve surgery was associated with lower mortality than either percutaneous coronary intervention or medical treatment alone.

Comparison of the prognostic value of regadenoson and adenosine myocardial perfusion imaging.

BACKGROUND: Regadenoson is now widely used in single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). However, the prognostic value of abnormal stress perfusion findings with regadenoson vs adenosine are unclear. The aim of this study was to evaluate the prognostic value of regadenoson SPECT and to compare it to that of adenosine SPECT. METHODS AND RESULTS: 3698 consecutive patients undergoing either adenosine or regadenoson SPECT were assessed at 1 year for the endpoints of cardiovascular death and a composite endpoint of cardiovascular death or MI. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for agent was used to account for differences in baseline characteristics. Patients undergoing adenosine SPECT MPI had a significantly higher prevalence of smoking history, diabetes, hypertension, and prior myocardial infarction (P < .05, all). At 1 year of follow-up, there were 154 cardiovascular deaths and 204 with the composite endpoint of cardiovascular death or MI. Using IPW adjustment to propensity for agent in a model with stress agent, summed stress score (SSS) remained a significant predictor of the composite endpoint of cardiovascular death or MI (HR 1.36 CI 1.28-1.46; P < .0001) as well as cardiovascular death (HR 1.38 CI 1.28-1.49; P < .0001). The interaction of SSS with agent was not significant. Similar findings were seen with summed difference score (SDS). CONCLUSIONS: SSS derived from either adenosine or regadenoson SPECT MPI is a significant predictor of events and provides incremental prognostic information beyond basic clinical variables. We have shown for the first time that use of regadenoson vs adenosine as stress agent does not modify the prognostic significance of SSS. Similar findings were seen with SDS.

Clinical outcome as a function of the PR-interval-there is virtue in moderation: data from the Duke Databank for cardiovascular disease.

AIMS: Recently, a U-shaped association between PR-interval and the risk of developing atrial fibrillation was described, with higher risk in patients with long and short PR-intervals. Little is known regarding the association of PR-interval duration and mortality. The objective of the current study was to explore the relationship between PR-interval and major cardiovascular outcomes in patients with known coronary heart disease. METHODS AND RESULTS: Patients in sinus rhythm, undergoing coronary angiography at Duke University Medical Center between 1989 and 2010, who had significant stenosis in at least one native coronary artery, were included. Patients with arrhythmia, second- or third-degree AV-block, QRS > 120 ms were excluded. A total of 9,637 patients were included (median age 63, IQR 55-71 years, 67% men). After adjustment for relevant covariates, the risk of a CV event increased with a decreasing PR-interval (10 ms decrements) for PR-interval values <162 ms (all-cause mortality; HR 1.057, 95% CI 1.019-1.096, P = 0.0030, composite of death or stroke; HR 1.047, 95% CI 1.011-1.085, P = 0.0095 and composite of cardiovascular death or cardiovascular rehospitalization; HR 1.032, 95% CI 1.002-1.063, P = 0.0387). No statistically significant changes in the risk associated with PR-interval for values >162 ms were seen for any of the studied endpoints. CONCLUSION: In patients with coronary heart disease, a prolongation of the PR-interval was not independently associated with poor outcomes, but a PR-interval shorter than normal was associated with increased all-cause mortality and other major cardiovascular events.

Influence of QRS infarct score and QRS duration prior to transcatheter aortic valve replacement on follow-up left ventricular end systolic volume in patients with new persistent left bundle branch block.

BACKGROUND: New-onset left bundle branch block (LBBB) is a known complication during Transcatheter Aortic Valve Replacement (TAVR). This study evaluated the influence of pre-TAVR cardiac conditions on left ventricular functions in patients with new persistent LBBB post-TAVR. METHODS: Only 11 patients qualified for this study because of the strict inclusion criteria. Pre-TAVR electrocardiograms were evaluated for Selvester QRS infarct score and QRS duration, and left ventricular end-systolic volume (LVESV) was used as outcome variable. RESULTS: There was a trend towards a positive correlation between QRS score and LVESV of r=0.59 (p=0.058), while there was no relationship between QRS duration and LVESV (r=-0.18 [p=0.59]). CONCLUSION: This study showed that patients with new LBBB and higher pre-TAVR QRS infarct score may have worse post-TAVR left ventricular function, however, pre-TAVR QRS duration has no such predictive value. Because of the small sample size these results should be interpreted with caution and assessed in a larger study population.

Use of antiarrhythmic drug therapy and clinical outcomes in older patients with concomitant atrial fibrillation and coronary artery disease.

AIMS: Atrial fibrillation (AF) and coronary artery disease (CAD) are common in older patients. We aimed to describe the use of antiarrhythmic drug (AAD) therapy and clinical outcomes in these patients. METHODS AND RESULTS: We analysed AAD therapy and outcomes in 1738 older patients (age ≥65) with AF and CAD in the Duke Databank for cardiovascular disease. The primary outcomes were mortality and rehospitalization at 1 and 5 years. Overall, 35% of patients received an AAD at baseline, 43% were female and 85% were white. Prior myocardial infarction (MI, 31%) and heart failure (41%) were common. Amiodarone was the most common AAD (21%), followed by pure Class III agents (sotalol 6.3%, dofetilide 2.2%). Persistence of AAD was low (35% at 1 year). After adjustment, baseline AAD use was not associated with 1-year mortality [adjusted hazard ratio (HR) 1.23, 95% confidence interval (CI) 0.94-1.60] or cardiovascular mortality (adjusted HR 1.27, 95% CI 0.90-1.80). However, AAD use was associated with increased all-cause rehospitalization (adjusted HR 1.20, 95% CI 1.03-1.39) and cardiovascular rehospitalization (adjusted HR 1.20, 95% CI 1.01-1.43) at 1 year. This association did not persist at 5 years; however, these patients were at very high risk of death (55% for those >75 and on AAD) and all-cause rehospitalization (87% for those >75 and on AAD) at 5 years. CONCLUSIONS: In older patients with AF and CAD, antiarrhythmic therapy was associated with increased rehospitalization at 1 year. Overall, these patients are at high risk of longer-term hospitalization and death. Safer, better-tolerated, and more effective therapies for symptom control in this high-risk population are warranted.

Warfarin use and long-term outcomes in patients with acute myocardial infarction and atrial fibrillation.

Warfarin use in patients with acute myocardial infarction (AMI) and atrial fibrillation (AF) remains challenging. We describe use of warfarin up to 1 year after hospitalization among patients with AMI and AF according to stroke and bleeding risk, and identify factors associated with long-term mortality in this population. Patients with AMI and AF who underwent cardiac catheterization during their AMI hospitalization in 1995-2007 were identified from the Duke Databank for Cardiovascular Disease. Warfarin use at discharge, 6 months, and 1 year as well as long-term vital status were assessed by surveys. Rates of warfarin use were presented according to CHADS2 and CHA2DS2VASc stroke and ATRIA bleeding risk scores. Cox proportional hazards modeling was used to determine whether warfarin use at discharge was independently associated with 1-year mortality. A total of 879 patients hospitalized with AMI with AF were identified. Median age was 72 (25th, 75th percentiles: 64, 79), and median follow-up was 4.1 years (1.3, 7.4). The rate of warfarin use at discharge was 24 % and did not differ by CHADS2, CHA2DS2VASc, or ATRIA risk scores. Warfarin use remained similar at 6 months (26 %) and 1 year (27 %). Long-term mortality was high and did not differ by whether warfarin was or was not prescribed at discharge (72 and 71 %, respectively). Factors associated with 1-year mortality were history of heart failure (HR 1.58, 95 % CI 1.32-1.90), higher Charlson comorbidity index (HR 1.19, 95 % CI 1.11-1.28), and older age (HR 1.03 per 1-year increase, 95 % CI 1.02-1.05). Warfarin use at discharge among patients hospitalized for AMI who had comorbid AF was low and remained low at 1 year. Warfarin use at hospital discharge was not associated with either 1-year mortality or long-term mortality.

Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction.

IMPORTANCE: Little information exists about the anatomical characteristics and clinical relevance of non-infarct-related artery (IRA) disease among patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: To investigate the incidence, extent, and location of obstructive non-IRA disease and compare 30-day mortality according to the presence of non-IRA disease in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of patients pooled from a convenience sample of 8 independent, international, randomized STEMI clinical trials published between 1993 and 2007. Follow-up varied from 1 month to 1 year. Among 68,765 patients enrolled in the trials, 28,282 patients with valid angiographic information were included in this analysis. Obstructive coronary artery disease was defined as stenosis of 50% or more of the diameter of a major epicardial artery. To assess the generalizability of trial-based results, external validation was performed using observational data for patients with STEMI from the Korea Acute Myocardial Infarction Registry (KAMIR) (between November 1, 2005, and December 31, 2013; n = 18,217) and the Duke Cardiovascular Databank (between January 1, 2005, and December 31, 2012; n = 1812). MAIN OUTCOMES AND MEASURES: Thirty-day mortality following STEMI. RESULTS: Overall, 52.8% (14,929 patients) had obstructive non-IRA disease; 29.6% involved 1 vessel and 18.8% involved 2 vessels. There was no substantial difference in the extent and distribution of non-IRA disease according to the IRA territory. Unadjusted and adjusted rates of 30-day mortality were significantly higher in patients with non-IRA disease than in those without non-IRA disease (unadjusted, 4.3% vs 1.7%, respectively; risk difference, 2.7% [95% CI, 2.3% to 3.0%], P < .001; and adjusted, 3.3% vs 1.9%, respectively; risk difference, 1.4% [95% CI, 1.0% to 1.8%], P < .001). The overall prevalence and association of non-IRA disease with 30-day mortality was consistent with findings from the KAMIR registry (adjusted, 3.6% for patients with non-IRA disease vs 2.5% in those without it; risk difference, 1.1% [95% CI, 0.6% to 1.7%]; P < .001), but not with the Duke database (adjusted, 4.7% with non-IRA disease vs 4.3% without it; risk difference, 0.4% [95% CI, -1.4% to 2.2%], P = .65). CONCLUSIONS AND RELEVANCE: In a retrospective pooled analysis of 8 clinical trials, obstructive non-IRA disease was common among patients presenting with STEMI, and was associated with a modest statistically significant increase in 30-day mortality. These findings require confirmation in prospectively designed studies, but raise questions about the appropriateness and timing of non-IRA revascularization in patients with STEMI.