Tricuspid Valve Regurgitation Immediately After Heart Transplant and Long-Term Outcomes.

BACKGROUND: Tricuspid valve regurgitation (TR) is a common finding immediately after cardiac transplantation. However, there is a scarcity of data regarding its implication if left untreated on long-term outcomes and the role of early surgical repair. METHODS: We retrospectively reviewed the Duke University Medical Center transplant database from January 2000 to June 2012 and identified 542 patients who underwent orthotropic heart transplantation. Patients were excluded if they underwent surgical repair for TR during the transplant or if the transplant was part of a multiorgan transplant or redo heart transplantation. TR was assessed intraoperatively after weaning from cardiopulmonary bypass. Independent variables were grade of TR and changes in TR grade during follow-up. TR grades were classified as insignificant (none or mild) versus significant (moderate or severe). Survival and need for posttransplant valve repair during follow-up were assessed. RESULTS: Significant TR was detected in 114 patients (21%) after weaning from cardiopulmonary bypass, with no significant difference in preoperative recipient pulmonary vascular resistance. Significant TR was associated with increased maximum postoperative plasma creatinine (median [interquartile range], 2.2 [1.5 to 3.2] mg/dL vs 1.8 [1.4 to 2.6] mg/dL, p = 0.008), prolonged postoperative stay (median [interquartile range], 12 [9 to 21] days vs 10 [8 to 14] days; p < 0.001), and decreased adjusted survival. Significant TR regressed to insignificant in 91% of recipients by 1 year after transplant. Six recipients (1%) who had significant TR after cardiopulmonary bypass underwent delayed tricuspid valve repair for significant TR during follow-up. CONCLUSIONS: Significant TR is a common finding immediately after transplant and is associated with early morbidity and reduced adjusted survival. Most significant TR resolves by 1 year after transplant. Optimal algorithms for follow-up and treatment of significant TR after heart transplantation need to be defined.

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.

Comparative Efficacy of Coronary Revascularization Procedures for Multivessel Coronary Artery Disease in Patients With Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease and death, yet little data exist regarding the comparative efficacy of coronary revascularization procedures in CKD patients with multivessel disease. We created a cohort of 4,687 adults who underwent cardiac catheterization, had a serum creatinine value measured within 30 days, and had more than one vessel with ≥50% stenosis. We used Cox proportional hazard regression modeling weighted by the inverse probability of treatment to examine the association between 4 treatment strategies (medical management, percutaneous coronary intervention [PCI] with bare metal stent, PCI with drug-eluting stent, and coronary artery bypass grafting [CABG]) and mortality among patients across categories of estimated glomerular filtration rate; secondary outcome was a composite of mortality, myocardial infarction, or revascularization. Compared with medical management, CABG was associated with a reduced risk of death for patients of any nondialysis CKD severity (hazard ratio [HR] range 0.43 to 0.59). There were no significant mortality differences between CABG and PCI, except a decreased death risk in CABG-treated CKD patients (HR range 0.54 to 0.55). Compared with medical management and PCI, CABG was associated with a lower risk of death, myocardial infarction, or revascularization in nondialysis CKD patients (HR range 0.41 to 0.64). There were similar associations between decreased estimated glomerular filtration rate and increased mortality across all multivessel coronary artery disease patient treatment groups. When accounting for treatment propensity, surgical revascularization was associated with improved outcomes in patients of all CKD severities. A prospective randomized trial in CKD patients is required to confirm our findings.

Revascularization Strategies and Outcomes in Elderly Patients With Multivessel Coronary Disease.

BACKGROUND: Balancing risks and benefits of revascularization in elderly patients with multivessel coronary artery disease (CAD) is challenging. The appropriate revascularization strategy for elderly patients with multivessel CAD is unclear. METHODS: We used the Duke Databank for Cardiovascular Disease to identify patients aged 75 years or more who had multivessel disease and treatment with percutaneous coronary intervention or coronary artery bypass graft surgery (CABG) within 30 days of the index catheterization between October 1, 2003, and June 30, 2013. The primary outcome was a composite of all-cause death, myocardial infarction, and coronary revascularization through latest follow-up. Associations between bare-metal stents (BMS), drug-eluting stents (DES), CABG, and outcomes were determined using multivariable Cox proportional hazards modeling, adjusting for potential confounders with CABG as the reference. Comparisons between BMS and DES were done using BMS as the reference. RESULTS: We identified 763 patients who met the criteria (BMS, n = 202; DES, n = 411; CABG, n = 150). The median age was 79 years (interquartile range, 76 to 82), and the median follow-up was 6.28 years. After adjustment, both BMS and DES were associated with a higher risk of the primary outcome. The BMS versus CABG hazard ratio was 1.58 (95% confidence interval: 1.15 to 2.19, p = 0.01). The DES versus CABG hazard ratio was 1.45 (95% confidence interval: 1.08 to 1.95, p = 0.01). The adjusted hazard ratio for DES versus BMS (0.92, 95% confidence interval: 0.71 to 1.19, p = 0.51) was not statistically significant. CONCLUSIONS: In this single-center analysis of 763 elderly patients with multivessel disease, CABG was associated with the best overall clinical outcomes, but was selected for a minority of patients. An adequately powered, randomized trial should be considered to define the best treatment strategy for this population.

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.

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.

Temporal Trends in Disease Severity and Predicted Surgical Risk at the Time of Referral for Echocardiography in Patients Diagnosed with Aortic Stenosis.

BACKGROUND: Calcific aortic stenosis (AS) is the most common underlying pathology in patients undergoing heart valve surgery, with an expected increasing prevalence among the aging population. METHODS AND RESULTS: We identified the temporal trends in referral patterns, disease severity, and associated surgical risk among patients with AS between January 1, 1995 and December 31, 2012 at the Duke University Hospital. A total of 6103 patients had a finding of mild (n = 3303), moderate (n = 1648), or severe AS (n = 1152) in a native aortic valve. Overall presence of severe AS increased significantly over time (P = 0.009) with the most substantial increase occurring from 2010 and onward. Median age upon referral (P < 0.001) and attendant predicted surgical risk (P < 0.001) increased significantly in the observation period among patients with a finding of severe AS. Among patients with a finding of severe AS, the proportion of patients aged older than 80 years increased to 51.0% in the most recent time period (2010-2012) compared with 32.6% in the preceding time period (P < 0.001 for overall time trend). Similarly, the proportion of patients with a logistic EuroSCORE greater than 20% increased to 21.3% (2010-2012) from 12.1% (pre-2010). CONCLUSIONS: Among patients referred for echocardiography to a high-volume tertiary hospital center, a significant increase in the prevalence of severe AS was observed over time. This trend occurred in parallel with increasing age and predicted surgical risk at referral. Health-care resource planning should account for an increasing number of patients in need of high-risk aortic valve replacements in the near future.

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.

Uso de agentes antiarrítmicos y resultados clínicos en pacientes añosos con fibrilación auricular y enfermedad coronaria concomitante

Objetivo: la fibrilación auricular (FA) y la enfermedad coronaria (EC) son comunes en los pacientes añosos. En este estudio nos propusimos describir el uso de agentes antiarrítmicos (AAA) y los resultados clínicos en estos pacientes. Métodos y resultados: se analizó el tratamiento con AAA y los resultados observados en 1.738 pacientes mayores (edad ³65) con FA y EC registrados en el Banco de Datos para Enfermedad Cardiovascular de Duke. Los resultados primarios fueron mortalidad y rehospitalización al año y a los cinco años. En términos generales, 35% de los pacientes recibían un AAA al inicio, 43% eran mujeres y 85% eran blancos. Fueron frecuentes los antecedentes de infarto de miocardio (IM, 31%) e insuficiencia cardíaca (41%). La amiodarona era el AAA más frecuente (21%), seguida de agentes de Clase III pura (sotalol 6,3%, dofetilida 2,2%). La persistencia de los AAA fue baja (35% al año). Luego del ajuste, el uso de AAA al inicio no se asoció con la mortalidad al año (cociente de riesgo ajustado (HR) 1,23, intervalo de confianza (IC) 95%: 0,94-1,60) o con la mortalidad cardiovascular (HR ajustado 1,27, IC 95% 0,90-1,80). Sin embargo, el uso de AAA sí se asoció con un aumento de la rehospitalización por todas las causas (HR ajustado 1,20, IC 95%: 1,03-1,39) y rehospitalización cardiovascular (HR ajustado 1,20, IC 95% 1,01-1,43) al año. Esta asociación no se mantiene a los cinco años; sin embargo, estos pacientes tuvieron un elevado riesgo de muerte (55% para los >75 años y que recibían AAA) y rehospitalización (87% para aquellos >75 años que recibían AAA) a los cinco años. Conclusiones: en pacientes añosos que padecen FA y EC, la terapia antiarrítmica se acompañó de aumento de la rehospitalización al año. En términos generales, estos pacientes presentan un alto riesgo de internación y muerte a largo plazo. Se necesitan desarrollar terapias más seguras, mejor toleradas y que brinden un control de los síntomas más eficaz en esta población de alto riesgo.

Predictors of long-term clinical endpoints in patients with refractory angina.

BACKGROUND: Clinical outcomes in patients with refractory angina (RA) are poorly characterized and variably described. Using the Duke Database for Cardiovascular Disease (DDCD), we explored characteristics that drive clinical endpoints in patients with class II to IV angina stabilized on medical therapy. METHODS AND RESULTS: We explored clinical endpoints and associated costs of patients who underwent catheterization at Duke University Medical Center from 1997 to 2010 for evaluation of coronary artery disease (CAD) and were found to have advanced CAD ineligible for additional revascularization, and were clinically stable for a minimum of 60 days. Of 77 257 cardiac catheterizations performed, 1908 patients met entry criteria. The 3-year incidence of death; cardiac rehospitalization; and a composite of death, myocardial infarction, stroke, cardiac rehospitalization, and revascularization were 13.0%, 43.5%, and 52.2%, respectively. Predictors of mortality included age, ejection fraction (EF), low body mass index, multivessel CAD, low heart rate, diabetes, diastolic blood pressure, history of coronary artery bypass graft surgery, cigarette smoking, history of congestive heart failure (CHF), and race. Multivessel CAD, EF<45%, and history of CHF increased risk of mortality; angina class and prior revascularization did not. Total rehospitalization costs over a 3-year period per patient were $10 185 (95% CI 8458, 11912) in 2012 US dollars. CONCLUSIONS: Clinically stable patients with RA who are medically managed have a modest mortality, but a high incidence of hospitalization and resource use over 3 years. These findings point to the need for novel therapies aimed at symptom mitigation in this population and their potential impact on health care utilization and costs.

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.

Twenty-five-year outcomes after multiple internal thoracic artery bypass.

OBJECTIVE: Coronary artery bypass grafting with multiple internal thoracic artery grafts is currently controversial. This study assessed single institutional outcomes with multiple internal thoracic artery grafting for guidance with future clinical decisions. METHODS: In 19,482 patients undergoing multivessel coronary artery bypass grafting (1984-2009), baseline characteristics were recorded in a prospective databank, and follow-up was obtained by questionnaires, phone contact, or National Death Index. Outcomes examined were subsequent myocardial infarction, percutaneous coronary intervention, reoperative coronary artery bypass grafting, all-cause death, and a composite of the 4. Three groups were defined: (1) no internal thoracic artery graft (1874/19,482 or 9%); (2) single internal thoracic artery grafts and adjunctive venous conduits (single internal thoracic artery; 16,881/19,482 or 87%); and (3) multiple internal thoracic artery grafts (728/19,482 or 4%). Multivariable Cox modeling adjusted for differences in baseline characteristics, and comparisons were performed using area under the curve analysis. RESULTS: Differences in baseline characteristics for the no internal thoracic artery graft, single internal thoracic artery, and multiple internal thoracic artery groups were as follows: median age 66, 64, and 59 years, respectively; congestive heart failure 22%, 18%, and 13%, respectively; ejection fraction 0.50, 0.52, and 0.51, respectively; reoperation 10%, 3%, and 7%, respectively; diabetes 27%, 30%, and 15%, respectively; and female gender 33%, 28%, and 20%, respectively. No differences existed in the median number of diseased vessels (3, 3, and 3, respectively) or number of grafts per patient (3, 3, and 3, respectively). Composite outcome improved with increasing internal thoracic artery grafts, whether assessing unadjusted or risk-adjusted data. Compared with no internal thoracic artery graft, the adjusted hazard ratio was 0.79 (confidence interval, 0.74-0.83) for single internal thoracic artery grafting and 0.70 (confidence interval, 0.62-0.80) for multiple internal thoracic artery grafting (both P < .001), reducing risk by 21% and 30%, respectively. CONCLUSIONS: This study confirms improved patient outcomes with multiple internal thoracic artery grafting, achieving half again as much benefit as single internal thoracic artery grafting alone. The data suggest that increasing application of multiple internal thoracic artery grafting should be encouraged to mitigate the inherent risks and costs of long-term cardiac events.

Ischemia change in stable coronary artery disease is an independent predictor of death and myocardial infarction.

OBJECTIVES: The aim of this study was to evaluate the independent prognostic significance of ischemia change in stable coronary artery disease (CAD). BACKGROUND: Recent randomized trials in stable CAD have suggested that revascularization does not improve outcomes compared with optimal medical therapy (MT). In contrast, the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found that revascularization led to greater ischemia reduction and suggested that this may be associated with improved unadjusted outcomes. Thus, the effects of MT versus revascularization on ischemia change and its independent prognostic significance requires further investigation. METHODS: From the Duke Cardiovascular Disease and Nuclear Cardiology Databanks, 1,425 consecutive patients with angiographically documented CAD who underwent 2 serial myocardial perfusion single-photon emission computed tomography scans were identified. Ischemia change was calculated for patients undergoing MT alone, percutaneous coronary intervention, or coronary artery bypass grafting. Patients were followed for a median of 5.8 years after the second myocardial perfusion scan. Cox proportional hazards regression modeling was used to identify factors independently associated with the primary outcome of death or myocardial infarction (MI). Formal risk reclassification analyses were conducted to assess whether the addition of ischemia change to traditional predictors resulted in improved risk classification for death or MI. RESULTS: More MT patients (15.6%) developed ≥5% ischemia worsening compared with those undergoing percutaneous coronary intervention (6.2%) or coronary artery bypass grafting (6.7%) (p < 0.001). After adjustment for established predictors, ≥5% ischemia worsening remained a significant independent predictor of death or MI (hazard ratio: 1.634; p = 0.0019) irrespective of treatment arm. Inclusion of ≥5% ischemia worsening in this model resulted in significant improvement in risk classification (net reclassification improvement: 4.6%, p = 0.0056) and model discrimination (integrated discrimination improvement: 0.0062, p = 0.0057). CONCLUSIONS: In stable CAD, ischemia worsening is an independent predictor of death or MI, resulting in significantly improved risk reclassification when added to previously known predictors.

Long-term survival of patients with ischemic cardiomyopathy treated by coronary artery bypass grafting versus medical therapy.

BACKGROUND: We prospectively applied the Surgical Treatment of Ischemic Cardiomyopathy trial entry criteria to an observational database to determine whether coronary artery bypass grafting (CABG) decreases mortality compared with medical therapy (MED) for patients with coronary artery disease and depressed left ventricular ejection fraction. METHODS: This was a retrospective, observational, cohort study of prospectively collected data from the Duke Databank for Cardiovascular Disease. Long-term mortality was the main outcome measure. Between January 1, 1995, and July 31, 2009, 86,874 patients underwent cardiac catheterization for suspected ischemic heart disease and were evaluated for inclusion in the analysis. RESULTS: A total of 2,624 patients were found to have left ventricular ejection fraction less than 0.35, coronary artery disease amenable to CABG, and no left main stenosis of greater than 50%. After exclusions including ongoing Canadian Cardiovascular Society class III angina and acute myocardial infarction, 763 patients were included for propensity score analysis, including 624 who received MED and 139 who underwent CABG. Adjusted mortality curves were constructed for those patients in the three quintiles most likely to receive CABG. The curves diverged early, with risk-adjusted mortality rates at 5 years of 46% for MED versus 29% for CABG, and the survival benefit of CABG over MED continued through 10 years of follow-up (hazard ratio, 0.63; 95% confidence interval, 0.45 to 0.88). CONCLUSIONS: Among a propensity-matched, risk-adjusted, observational cohort of patients with coronary artery disease, left ventricular ejection fraction less than 0.35, and no left main disease of greater than 50%, CABG is associated with a survival advantage over MED through 10 years of follow-up.

Relationship of the time interval between cardiac catheterization and elective coronary artery bypass surgery with postprocedural acute kidney injury.

BACKGROUND: Some prior studies have suggested that the time to cardiac surgery after cardiac catheterization is inversely related to postoperative acute kidney injury (AKI). However, these studies, because of the small number of patients, were unable to adequately account for patient case-mix and included both those undergoing elective surgery and those undergoing urgent surgery. METHODS AND RESULTS: We examined data on 2441 consecutive patients undergoing elective coronary artery bypass surgery (CABG) after cardiac catheterization. The association of post-CABG AKI (defined as increase in post-CABG serum creatinine ≥ 50% above baseline or the need for new dialysis) and time between cardiac catheterization and CABG was evaluated using multivariable logistic regression modeling. AKI occurred in 17.1% of CABG patients. The risk of AKI was highest in patients in whom CABG was performed ≤ 1 day after cardiac catheterization (adjusted mean rates [95% CI]: 24.0% [18.0%, 30.9%], 18.4% [14.8%, 22.5%], 17.3% [13.3%, 21.9%], 16.4% [12.6%, 20.8%], and 15.8% [13.7%, 18.0%] for days ≤ 1, 2, 3, 4, and ≥ 5, respectively; P=0.019 for test of trend). Post-CABG AKI was associated with increased risk of long-term death (hazard ratio 1.268, 95% CI 1.093, 1.471). CONCLUSIONS: The risk of post-CABG AKI was inversely and modestly related to the time between cardiac catheterization and CABG, with the highest incidence in those operated ≤ 1 day after cardiac catheterization despite their lower risk profile. Whether delaying elective CABG >24 hours of exposure to contrast agents (when feasible) has the potential for decreasing post-CABG AKI remains to be evaluated in future studies.

Impact of early surgery on survival of patients with severe mitral regurgitation.

BACKGROUND: Optimal timing of surgery in degenerative mitral regurgitation (MR) remains a controversial topic. The impact of current ACC/AHA guideline recommendations about optimal timing of surgery on outcomes is untested and contemporary data are lacking. OBJECTIVE: To assess the association between the timing of surgery and long-term survival in patients with severe MR. METHODS: A cohort of 481 patients with severe, degenerative mitral regurgitation (1995-2007) from the Duke Cardiovascular Disease Databank who fulfilled at least one ACC/AHA guideline indication for surgery was identified. Exclusion criteria were rheumatic disease, congenital mitral valve (MV) disease, hypertrophic cardiomyopathy, coronary disease in more than one vessel, endocarditis, other severe valve disease, h/o valve repair/replacement. Patients were grouped into early surgery (in ≤ 2 months of presenting with surgical indications) and late surgery (>2 months) groups. An adjusted Cox regression model was constructed for time to death after 2 months with a time-dependent covariate term for late surgery. RESULTS: 168 patients had early surgery (median time to surgery 0.42 months) with 153 followed up after 2 months, 94 had late surgery (median time to surgery 8.75 months) and 219 medically managed. 127/168 in the early surgery group and 84/94 in the late surgery group received MV repair (p=0.02). Over 5.6 years' (median) follow-up there were 35 deaths (21%) in the early surgery group, with two occurring before 2 months and 20 (21%) in the late group. In the multivariable model, those undergoing early surgery had a lower hazard for death than those who underwent late surgery (HR=0.54 (95% CI 0.30 to 0.97), p=0.039). MV repair was independently associated with survival (HR=0.45 (95% CI 0.25 to 0.83), p=0.01). CONCLUSIONS: In patients with severe MR who presented with guideline indications for surgery, those selected for earlier surgery had improved survival. These data support the current guidelines for early referral to surgery in patients with severe MR for enlarged left ventricular dimensions, reduced ejection fraction and symptoms rather than delaying surgery. Larger randomised trials are needed to definitively answer the question of optimal timing of surgery in patients with severe degenerative MR.

Impact of recovery of renal function on long-term mortality after coronary artery bypass grafting.

Whether prognosis differs in acute renal failure (ARF) after coronary artery bypass grafting (CABG) in patients with and without recovery of renal function is not known. We studied patients who had CABG at Duke University Medical Center (1995 to 2008). ARF was defined as an increase in peak creatinine ≥50% after CABG or ≥0.7 mg/dl above baseline or need for new dialysis. Patients were categorized into 3 groups: (1) no ARF after CABG, (2) ARF after CABG and completely recovered renal function at day 7 (return of creatinine to no higher than baseline and no dialysis), or (3) ARF after CABG with no recovery of renal function at day 7 (creatinine no higher than baseline or new dialysis). Main outcome measurement was risk-adjusted long-term mortality (excluding death ≤7 days). ARF after CABG occurred in 2,083 of 10,415 patients (20%) and completely recovered in 703 (33.7%). Risk-adjusted mortality was highest in patients with ARF without recovery of renal function (hazard ratios 1.47, 95% confidence interval 1.34 to 1.62) and intermediate in those with ARF but completely recovered renal function (hazard ratios 1.21, 95% confidence interval 1.07 to 1.37, referent no-ARF group). Mortality was lower in patients with ARF compared to those without complete recovery of renal function (p = 0.0083). In conclusion, in patients with ARF after CABG, complete recovery of renal function was associated with significantly lower long-term mortality compared to those without such recovery, although this was significantly higher than in those without ARF. Thus, major emphasis should be on prevention of ARF in patients undergoing CABG.

Influence of patient age on procedural selection in mitral valve surgery.

BACKGROUND: Previous studies suggest that mitral valve replacement is comparable to repair in the elderly, and a national trend exists toward tissue valves. However, few direct comparison data are available, and this study evaluated the effects of patient age on risk-adjusted survival after mitral procedures. METHODS: From 1986 to 2006, 2,064 patients underwent isolated primary mitral operations (±CABG). Maximal follow-up was 20 years with a median of 5 years. Valve disease etiology was the following: degenerative, 864; ischemic, 450; rheumatic, 416; endocarditis, 98; and "other," 236. Overall, 58% had repair and 39% had concomitant coronary artery bypass grafting. Survival differences were evaluated with a Cox proportional hazards model that included baseline characteristics, valve disease etiology, and choice of repair versus replacement with tissue or mechanical valves. RESULTS: Baseline risk profiles generally were better for mechanical valves, and age was the most significant multivariable predictor of late mortality [hazard ratio = 1.4 per 10-year increment, Wald χ(2) = 32.7, p < 0.0001]. As compared with repair, risk-adjusted survival was inferior with either tissue valves [1.8, 27.6, <0.0001] or mechanical valves [1.3, 8.1, 0.0044], and no treatment interaction was observed with age (p = 0.18). At no patient age did tissue valves achieve equivalent survival to either repair or mechanical valves. CONCLUSIONS: Mitral repair is associated with better survival than valve replacement across the spectrum of patient age. If replacement is required, mechanical valves achieve better outcomes, even in the elderly. These data suggest that tissue valves should be reserved only for patients with absolute contraindications to anticoagulation who are not amenable to repair.

STICH (Surgical Treatment for Ischemic Heart Failure) trial enrollment.

OBJECTIVES: The aim of this study was to assess the influence of enrolling site location and enrollment performance on the generalizability of STICH (Surgical Treatment for Ischemic Heart Failure) trial results. BACKGROUND: The international STICH trial seeks to define the role of cardiac surgery for patients with ischemic cardiomyopathy. METHODS: Baseline characteristics of 2,136 randomized STICH patients were entered into a multivariate equation created using the Duke Databank for Cardiovascular Diseases to predict their 5-year risk for death without cardiac surgery. Patients ordered by increasing predicted risk were assigned to 1 of 32 risk at randomization (RAR) groups created to share one-thirty-second of total predicted deaths. Numbers of patients sharing the same RAR group were compared between higher and lower enrolling site groupings and for countries tending to enroll high- or low-risk patients. RESULTS: Country of enrollment was a stronger determinant of risk diversity than site enrollment performance among patients enrolled at 127 sites in 26 countries. Mean RAR differences among countries ranged from 9.4 (Singapore) to 18.6 (Germany). However, 1,614 of 2,136 patients (76%) from countries enrolling lower-risk patients shared the same RAR group with patients from countries enrolling higher-risk patients. Baseline characteristics responsible for risk differences of patients enrolled in the 2 country groupings were sufficiently similar to exert little influence on clinical decision making. CONCLUSIONS: STICH randomized patients are characterized by a continuous spectrum of risk, without discordant dominance from any site or country. Clinical site diversity promises to enhance the generalization of STICH trial results to a broad population of patients with ischemic cardiomyopathy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease; NCT00023595).