Gautam R. Shroff

Long-Term Survival and Repeat Coronary Revascularization in Dialysis Patients After Surgical and Percutaneous Coronary Revascularization With Drug-Eluting and Bare Metal Stents in the United States

Background— Few published data describe long-term survival of dialysis patients undergoing surgical versus percutaneous coronary revascularization in the era of drug-eluting stents (DES). Methods and Results— Using United States Renal Data System data, we identified 23 033 dialysis patients who underwent coronary revascularization (6178 coronary artery bypass grafting, 5011 bare metal stents, 11 844 DES) from 2004 to 2009. Revascularization procedures decreased from 4347 in 2004 to 3344 in 2009. DES use decreased by 41% and bare metal stent use increased by 85% from 2006 to 2007. Long-term survival was estimated by the Kaplan-Meier method, and independent predictors of mortality were examined in a comorbidity-adjusted Cox model. In-hospital mortality for coronary artery bypass grafting patients was 8.2%; all-cause survival at 1, 2, and 5 years was 70%, 57%, and 28%, respectively. In-hospital mortality for DES patients was 2.7%; 1-, 2-, and 5-year survival was 71%, 53%, and 24%, respectively. Independent predictors of mortality were similar in both cohorts: age >65 years, white race, dialysis duration, peritoneal dialysis, and congestive heart failure, but not diabetes mellitus. Survival was significantly higher for coronary artery bypass grafting patients who received internal mammary grafts (hazard ratio, 0.83; P<0.0001). The probability of repeat revascularization accounting for the competing risk of death was 18% with bare metal stents, 19% with DES, and 6% with coronary artery bypass grafting at 1 year. Conclusions— Among dialysis patients undergoing coronary revascularization, in-hospital mortality was higher after coronary artery bypass grafting, but long-term survival was superior with internal mammary grafts. In-hospital mortality was lower for DES patients, but the probability of repeat revascularization was higher and comparable to that in patients receiving a bare metal stent. Revascularization decisions for dialysis patients should be individualized.

Survival of patients on dialysis having off-pump versus on-pump coronary artery bypass surgery in the United States.

BACKGROUND Patients on dialysis sustain at least a threefold higher in-hospital mortality rate and markedly higher long-term mortality following coronary artery bypass graft surgery than the general population. Smaller studies have suggested that dialysis patients have superior outcomes with off-pump compared with on-pump coronary artery bypass surgery. METHODS From the United States Renal Data System database, 13,085 patients on dialysis having first coronary artery bypass surgery between 2001 and 2006 were identified. Of these, 2335 (17.8%) had off-pump coronary artery bypass surgery. The Kaplan-Meier method was used to estimate survival of patients having off-pump coronary artery bypass and patients having on-pump coronary artery bypass. A Cox proportional hazards model was used to assess effects of off-pump coronary artery bypass on mortality with adjustment for baseline patient characteristics. RESULTS Off-pump coronary artery bypass surgery was associated with significantly reduced all-cause mortality compared with on-pump coronary artery bypass surgery (hazard ratio 0.92, 95% confidence interval 0.86-0.99, P = .02). The observed survival benefit was most notable in the first year after surgery (70.3% vs 68.7%) and was lost 2 years after surgery (55.4% vs 55.2%). No difference was noted in the in-hospital mortality rate with off-pump coronary artery bypass surgery versus on-pump coronary artery bypass surgery (9.7% vs 11.0%, P = .06). Cardiac mortality during the follow-up period was similar (23.6% vs 23.8%; adjusted hazard ratio 0.95, 95% confidence interval 0.86-1.04, P = .26). Use of internal thoracic grafts was independently associated with improved survival after coronary artery bypass surgery (hazard ratio, 0.92; 95% confidence interval, 0.87-0.98, P = .0057). CONCLUSIONS Patients on dialysis sustain high in-hospital and 2-year mortality rates after coronary artery bypass surgery. Off-pump coronary artery bypass is associated with modestly increased survival compared with on-pump coronary artery bypass, a benefit most marked early after off-pump coronary artery bypass.

Long-term Survival of Dialysis Patients With Bacterial Endocarditis Undergoing Valvular Replacement Surgery in the United States

Background— Bacterial endocarditis in dialysis patients is associated with high mortality rates. The literature is limited on the long-term outcomes of valvular replacement surgery and the choice of prosthesis in dialysis patients with bacterial endocarditis. Methods and Results— Dialysis patients hospitalized for bacterial endocarditis from 2004 to 2007 were studied retrospectively using data from the United States Renal Data System. Long-term survival of patients undergoing valve replacement surgery with tissue or nontissue valves was compared by use of the Kaplan-Meier method. A Cox proportional hazards model was used to identify independent predictors of mortality in patients undergoing valvular replacement surgery. During the study period, 11 156 dialysis patients were hospitalized for bacterial endocarditis and 1267 (11.4%) underwent valvular replacement surgery (tissue valve, 44.3%; nontissue valve, 55.7%). In the valve replacement cohort, 60% were men, 50% were white, 54% were 45 to 64 years of age, and 36% were diabetic. Estimated survival with tissue and nontissue valves at 0.5, 1, 2, and 3 years was 59% and 60%, 48% and 50%, 35% and 37%, and 25% and 30%, respectively (log-rank P=0.42). Staphylococcus was the predominant organism (66% of identified organisms). Independent predictors of mortality in patients undergoing valve replacement surgery included older age, diabetes mellitus as the cause of end-stage renal disease, surgery during index hospitalization, staphylococcus as the causative organism, and dysrhythmias as a comorbid condition. Conclusions— Valve replacement surgery is appropriate for well-selected dialysis patients with bacterial endocarditis but is associated with high mortality rates. Survival does not differ with tissue or nontissue prosthesis.

Outcomes of renal transplant and waiting list patients with bacterial endocarditis in the United States

BACKGROUND Bacterial endocarditis is associated with poor long-term survival among dialysis patients. Renal transplant patients and those waiting list for renal transplantation are predisposed to developing bacterial endocarditis; data regarding incidence and outcomes are limited. METHODS Patients hospitalised for bacterial endocarditis were identified from patients transplanted or waiting list between 1995 and 2003. Transplant and waiting list cohorts were derived from the United States Renal Data System (USRDS) database. All patients had Medicare as primary payer. Long-term survival was estimated by the Kaplan-Meier method. Cox proportional hazards analysis was used to identify independent predictors of bacterial endocarditis. RESULTS During the study period, 282 renal transplant patients and 549 waiting list patients were hospitalised with bacterial endocarditis. Incidence rates of bacterial endocarditis per 1000 patient-years were 5.6 among waiting list patients, 2.6 among deceased-donor transplant recipients and 1.8 among living-donor transplant recipients. In-hospital mortality rates were 16.0% for the renal transplant cohort and 18.6% for the waiting list cohort. Two-year post-endocarditis survival rates were 58% for transplant patients and 41% for waiting list patients. The most powerful predictors of bacterial endocarditis among transplant patients were donor age, patient age, diabetic end-stage renal disease (ESRD) and prior dialysis time longer than 2 years. CONCLUSIONS Renal transplant patients hospitalised with bacterial endocarditis sustain high in-hospital and long-term mortality rates. Waiting list patients are at higher risk of developing bacterial endocarditis than renal transplant recipients.

Impact of acute coronary syndromes on survival of dialysis patients following surgical or percutaneous coronary revascularization in the United States.

Aims: We sought to evaluate survival of dialysis (chronic kidney disease (CKD) stage 5D) patients undergoing coronary revascularization procedures in the context of acute coronary syndrome (ACS) compared with absence of ACS. Methods and results: CKD 5D patients undergoing coronary revascularization, 2004–2009 (n = 23,033), were identified from the United States Renal Data System. Long-term survival was estimated by the Kaplan–Meier method and independent predictors of mortality using a comorbidity-adjusted Cox proportional hazards model. Among ACS patients (n = 12,473; 54%), revascularization procedures were coronary artery bypass grafting (CABG, n = 2910), drug-eluting stents (DESs, n = 6566), and bare metal stents (BMSs, n = 2997). All-cause survival rates following these procedures, respectively, were: in-hospital 90%, 96%, 93%; one-year: 66%, 67%, 58%; two-year: 53%, 48%, 43%. Among non-ACS patients (n = 10,560; 46%), procedures were CABG (n = 3268), DESs (n = 5278), and BMSs (n = 2014). Survival rates following these procedures, respectively, were: in-hospital 94%, 99%, 98%; one year: 73%, 77%, 70%; two year: 61%, 59%, 55%. DESs (versus CABG) independently predicted mortality among ACS (hazard ratio 1.08; 95% confidence interval 1.02–1.15) but not non-ACS patients (1.01, 0.95–1.07); BMSs (versus CABG) independently predicted mortality among ACS (1.30, 1.21–1.38) and non-ACS (1.13, 1.05–1.22) patients. Conclusions: Among CKD 5D patients, survival was lower for ACS versus non-ACS indications following all revascularization strategies. CABG (versus DESs) was associated with higher long-term survival in the context of ACS; in the absence of ACS, long-term survival was similar after CABG or DESs. BMSs were consistently associated with worse outcomes.

Renal Function in Patients With Atrial Fibrillation Receiving Anticoagulants: The Canaries in the Coal Mine

The past few years have witnessed unprecedented progress in the field of anticoagulation for atrial fibrillation (AF). Since 2010, 4 direct oral anticoagulants (DOACs) have been approved in nonvalvular AF based on pivotal trials. Patients with advanced chronic kidney disease (CKD) are arguably the highest-risk patients receiving anticoagulation from the standpoint of both stroke/systemic embolism and bleeding events. Although patients with estimated creatinine clearance (eCrCl) less than 30 mL/min/1.73m2 (to convert to milliliters per second per meters squared, multiply by 0.0167) were excluded from trials, about 15% to 20% of enrollees had stage 3 CKD, providing clinicians representative data to derive meaningful conclusions to guide practice. Prespecified subgroup analysis and metaanalysis concur that the overall trial results (ie, noninferiority of the DOACs vs warfarin in the prevention of stroke/systemic embolism) are applicable to patients with stage 3 CKD, and several agents may actually have specific advantages.1 Not enough attention has been focused on systemic approaches to recognize and anticipate the fresh set of challenges that will be posed in the era of the DOACs, particularly in this high-risk population. Published scenarios raise doubts about our maturity as a health care system to safely adapt to this new world of anticoagulation. Data from a large dialysis database showed that nearly 6% of patients with AF undergoing long-term hemodialysis initiated therapy with dabigatran or rivaroxaban from 2010 to 2014.2 This is a troubling observation because these DOACs are not approved in dialysis patients owing to their exclusion from pivotal randomized clinical trials, and because use can be associated with heightened bleeding risk and erratic blood levels on dialysis. The DOACs were prescribed within 45 days of approval in the United States and steadily increased during the study period. Moreover, about 15% of dabigatran and 32% of rivaroxaban users were prescribed the full dose (without renal dose modification), whereas others received doses approved for patients with moderate CKD. Importantly, their use among hemodialysis patients was accompanied by serious consequences—higher associated risks of both major and fatal bleeding. A similar theme of enthusiastic prescription of dabigatran to dialysis patients was observed in data from the United States Renal Data System.3 In another example, hematologists in New Zealand carried out an audit of bleeding complications after introduction of dabigatran, reporting a higher occurrence of major bleeding episodes than would be anticipated from the representative randomized clinical trial.4 The authors concluded that errors by prescribers related to incorrect dosing/indication were major contributors in the context of clinical characteristics that affect accurate dosing (ie, higher age, impaired renal function). In these examples, the lack of recognition of the significance of underlying renal impairment was a unifying denominator. The CKD population is most vulnerable to needing dose adjustments because of the high renal clearance of the DOACs, ranging from 25% (apixaban) to 80% (dabigatran). A post hoc observation of the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial highlighted the temporal deterioration in eCrCl among all 3 study arms receiving longterm anticoagulation (highand low-dose dabigatran and warfarin), albeit statistically significant in the warfarin arm.5 This observation may lend credence to the notion of warfarin-related nephropathy/glomerulopathy, but more importantly perhaps, indicates the need for temporal monitoring of renal function during anticoagulant therapy for AF, particularly in patients with CKD. Although most clinicians use estimated glomerular filtration rates to monitor renal function in practice, the doses of DOACs are approved based on eCrCl values (CockroftGault equation). There is significant discordance in doses of some DOACs if estimated glomerular filtration rate is used to measure renal function instead of eCrCl; the discordance is higher for agents with greater renal clearance.6 These studies provide sobering forewarnings of the potential for clinical errors with use of DOACs among patients with CKD. As the coprevalence of AF and CKD steadily increases in an aging population, these examples will only become increasingly common. We need to couple our enthusiasm to adopt the DOACs with adequate systemwide measures to focus attention to prescriber education, achieving familiarity in their use and creating alerts to prevent errors. Although DOACs represent a huge advance in medical therapy, their use also involves a steep learning curve that could be unforgiving from a patient’s perspective. For clinicians who have long been accustomed to warfarin, without attendant need for significant dose adjustment in the face of kidney impairment and with the comfort of the availability of international normalized ratio (INR) levels to guide dosing changes, this is not a trivial change in perspective. Acute kidney injury is common among hospitalized patients, and it is now incumbent on inpatient health care professionals to actively recognize and ensure that dynamic dose adjustment of DOACs occurs consistently. Another important paradigm shift with the DOACs (relative to warfarin) is the rapid onset/offset of action, VIEWPOINT

Atherosclerotic versus nonatherosclerotic evaluation: the Yin and Yang of cardiovascular imaging in advanced chronic kidney disease.

Patients with advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD), represent both an enigma and a challenge to cardiovascular specialists. A gradient of increasing hazard of all-cause mortality with advancing degrees of CKD is well recognized. Reported adjusted mortality

Incidence of Acute Coronary Syndrome in the General Medicare Population, 1992 to 2009: A Real-World Perspective

2. Thomas RJ, King M, Lui K, Oldridge N, Piña IL, Spertus J; American Association of Cardiovascular and Pulmonary Rehabilitation/American College of Cardiology/American Heart Association Cardiac Rehabilitation/Secondary Prevention Performance Measures Writing Committee. AACVPR/ACC/AHA 2007 performance measures on cardiac rehabilitation for referral to and delivery of cardiac rehabilitation/secondary prevention services. Circulation. 2007;116(14):1611-1642.

Letter by Shroff and Orlandi regarding article, "Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of Myocardial Dysrhythmia After Cardiac Surgery) study".

To the Editor: We read with great interest the study by Patti and colleagues1 that suggests a beneficial effect of atorvastatin in preventing postoperative atrial fibrillation in cardiac surgery patients. The placebo arm in this study had fewer patients on β-blockers (60% versus 72%, P =0.08), more patients with left atrial …

Exploring the elusive link between subclinical fibrosis and clinical events in end-stage renal disease: does cardiac magnetic resonance imaging hold the key?

Extensive myocardial fibrosis is known to occur in patients undergoing dialysis due to a variety of mechanisms not necessarily restricted to coronary artery disease. Fibrosis may predispose to reentry arrhythmias and long-term myocardial dysfunction, and sudden death and congestive heart failure are the most frequent causes of death in patients undergoing renal replacement therapy. Despite the high accuracy of magnetic resonance for imaging of myocardial fibrosis, its use has been restricted by the risk of inducing nephrogenic systemic sclerosis with the injection of gadolinium. The development of new sequences that allow the detection and quantifying of the severity of extracellular myocardial fibrosis offers a chance to study the pathogenesis of this condition and identify potential interventions to retard or reverse it. Whether these will lead to an improved outcome needs to be prospectively tested.