Two-year results from Onyx ONE clear in patients with high bleeding risk on one-month DAPT with and without intracoronary imaging.

BACKGROUND: Patients with high bleeding risk (HBR) are often treated with abbreviated dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) to reduce bleeding risk, however this strategy is associated with an increase in ischemic events, especially if the acute PCI result is suboptimal. We compared clinical outcomes among patients with HBR treated with 1-month DAPT who underwent intravascular ultrasound (IVUS)- or optical coherence tomography (OCT)-guided PCI versus those who underwent angiography-guided PCI without intravascular imaging. METHODS: The Onyx ONE Clear study includes patients with HBR from the Onyx ONE US/Japan and Onyx ONE randomized studies who were treated with the Resolute Onyx zotarolimus-eluting stent. The primary endpoint was the composite of cardiac death (CD) or myocardial infarction (MI) between 1 month and 2 years after PCI. Propensity-score adjustments and matching were performed for differences in baseline and procedural characteristics between groups. RESULTS: Among the 1507 patients in Onyx ONE Clear, 271 (18.0 %) had IVUS or OCT used during PCI (Imaging-guided group) and 1236 (82.0 %) underwent Angiography-guided PCI (Angio-guided group). Imaging-guided patients were less likely to present with atrial fibrillation, acute coronary syndrome, and left ventricle ejection fraction ≤35 %. Conversely, Imaging-guided patients were more likely to have complex (ACC/AHA type B2/C), longer, and heavily calcified lesions. Between 1 month and 2 years, the composite rate of CD or MI was similar between Imaging-guided and Angio-guided patients (9.9 % vs. 12.4 %, P = 0.33). There was also no difference between groups after adjustment; (P = 0.56). However, CD was significantly lower among Imaging-guided patients (2.7 % vs. 6.1 %, P = 0.048). There were no between-group differences in MI or stent thrombosis. Propensity score matching results were similar. CONCLUSION: Despite higher lesion complexity, using intravascular imaging guidance for PCI between 1-month and 2-years follow-up had comparable outcomes with angiographic guidance alone in patients with HBR treated with 1-month DAPT. (ClinicalTrials.gov: Identifier: NCT03647475 and NCT03344653). NON-STANDARD ABBREVIATIONS AND ACRONYMS: BARC: Bleeding Academic Research Consortium; DAPT: dual antiplatelet therapy; DES: drug-eluting stent; HBR: high bleeding risk; IVUS: intravascular ultrasound; OCT: optical coherence tomography; SAPT: single antiplatelet therapy.

Readmission in Patients With ST-Elevation Myocardial Infarction in 4 Age Groups (<45, >45 to <60, 60 to <75, and >75).

The incidence of ST-elevation myocardial infarction (STEMI) among younger adults is increasing due to an increased prevalence of cardiometabolic risk factors. Readmissions after STEMI in young patients could lead to substantial health care costs and a significant burden on health care resources. Although STEMI readmissions are well studied in elderly patients, limited data are available regarding readmissions after STEMI in young patients and the etiologies remain poorly understood. Because younger patients with STEMI have different sociodemographic profiles th;an older patients with STEMI, one would postulate that the risk factors for readmissions in young patients would differ from that reported in the older patients with STEMI. We performed a contemporary nationwide study using the 2016 and 2017 Nationwide Readmissions Database to identify patterns of readmissions after STEMI in the young adult population. Our analysis of the Nationwide Readmissions Database revealed a total of 243,747 hospitalizations for STEMI between 2016 and 2017. Readmission rates demonstrated a steady increase from discharge, increasing to 7.8% at 30 days and 10.3% at 60 days before relatively plateauing at 12.1% at 90 days. Cardiovascular etiologies were the most common cause of readmission (53.6%). After multivariable analysis, development of cardiogenic shock (adjusted odds ratio 1.48, 95% confidence interval 1.11 to 1.97; p = 0.008) and acute renal failure (adjusted odds ratio 1.46, 95% confidence interval 1.14 to 1.87; p = 0.003) during the index admission were associated with significantly higher rates of readmission. In conclusion, close monitoring in young patients who presented with STEMI and concomitant with cardiogenic shock or acute renal failure, and possibly, aggressive therapy during index admission may be needed. However, this population may be heterogeneous and further research is needed.

The Prognostic Utility of Invasive Right Heart Catheterization in Patients Prior to Transcatheter Aortic Valve Replacement.

INTRODUCTION: Invasive right heart catheterization (RHC) provides valuable prognostic information in cases of severe aortic stenosis, but is not done routinely prior to transcatheter aortic valve replacement (TAVR). Therefore, we sought to investigate the prognostic utility of pre-TAVR RHC for assessing outcomes post TAVR. METHODS: This is a single-center, retrospective study of patients who underwent RHC prior to TAVR between June 2011 and March 2019. We evaluated abnormalities in the following variables as predictors of poor outcomes post TAVR: pulmonary capillary wedge pressure (PCWP), systolic pulmonary artery pressure (PASP), mixed venous oxygen saturation (MVO2), right ventricular stroke work index (RVSWI), and right atrial pressure (RAP). Cox proportional hazard regression models were used to assess the primary composite outcome of all-cause mortality and hospitalization for heart failure. RESULTS: A total of 522 patients (mean age, 83.5 ± 4.5 years; 49.4% women) with complete invasive hemodynamic data were included. At a median follow-up of 529.5 days, there were 127 deaths and 59 heart failure hospitalizations. On multivariate analysis, PCWP ≥15 mm Hg (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.02-2.07), PASP ≥50 mm Hg (HR, 1.66; 95% CI, 1.17-2.36), MVO2 ≤60% (HR, 1.42; 95% CI, 1.01-1.98), RVSWI ≥12 g•m/m²/beat (HR, 1.40; 95% CI, 1.004-1.94), and RAP ≥10 mm Hg (HR, 1.66; 95% CI, 1.09-2.51) were independent predictors of death or heart failure hospitalization. CONCLUSIONS: Preprocedural invasive RHC provides useful prognostic information. A comprehensive invasive hemodynamic assessment should be considered for risk stratification in patients undergoing TAVR.

Comparison of a Single Versus Double Perclose Technique for Percutaneous Transfemoral Transcatheter Aortic Valve Replacement.

BACKGROUND: The optimal strategy for arterial closure in percutaneous transfemoral transcatheter aortic valve replacement (TF-TAVR) remains under debate. METHODS: Single-center, prospective, observational study of consecutive patients undergoing TF-TAVR between March 2018 and December 2019 who underwent closure with an upfront single vs double Perclose device. Device success, access-site vascular, and bleeding complications were defined according to the Valvular Academic Research Consortium (VARC)-2 criteria. Inverse-probability of treatment weighting (IPTW) was used to balance baseline characteristics between groups. RESULTS: A total of 241 patients (mean age, 81.4 ± 8.5 years, 47% women) were included, of which 127 underwent an upfront single-Perclose (SP) strategy and 114 underwent an upfront double-Perclose (DP) strategy. Fifty-six percent of patients were treated with a CoreValve (Medtronic). The SP group was less likely to be on dialysis and on aspirin, but were more likely to receive a CoreValve, with larger valve sizes and larger delivery sheaths. Baseline characteristics were well balanced after IPTW adjustment. Device success rate was comparable between groups (96% in the SP group vs 93% in the DP group; P=.39). The SP technique was associated with fewer vascular complications (8.7% in the SP group vs 26.3% in the DP group; P<.01; IPTW relative risk [RR], 0.34; 95% confidence Interval [CI], 0.16-0.71) and bleeding complications (2.4% in the SP group vs 12.3% in the DP group; P<.01; IPTW RR, 0.21; 95% CI, 0.06-0.76) compared with the DP technique. There were no differences in 30-day mortality. CONCLUSION: An upfront SP technique is equally efficacious and not associated with increased vascular and bleeding complications compared with an upfront DP technique in patients undergoing percutaneous TF-TAVR.

The role of neighborhood disadvantage in predicting mortality in patients after transcatheter aortic valve replacement.

BACKGROUND: Neighborhoods have a powerful impact on health. Prior investigations into disparities associated with transcatheter aortic valve replacement (TAVR) have focused on race and access to the procedure. We sought to investigate the role of neighborhood disadvantage on mortality post-TAVR. METHODS: Patients who underwent TAVR at Kaiser Permanente Los Angeles Medical Center between June, 2011 and March, 2019 were evaluated. Neighborhood disadvantage was defined using the area deprivation index, an established and validated index that considers multiple socioeconomic metrics. Cutoffs used for disadvantage were national percentile ≥25% and state decile ≥6. Cox proportional hazards regression analysis was used to assess outcomes. RESULTS: A total of 668 patients (age 82.1 ± 7.5 years, 49% female) were included, of which 215 (32.2%) were from disadvantaged neighborhoods by state decile, and 167 (25%) by national percentile. At a median follow-up of 18.8 months (interquartile range 8.7-36.5 months), neighborhood disadvantage was independently associated with increased all-cause mortality (National percentile: hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.35-2.69; state decile: HR 1.68, 95% CI 1.21-2.34). On propensity scored analysis, neighborhood disadvantaged remained independently associated with increased all-cause mortality (National percentile: IPTW HR 1.86, 95% CI 1.52-2.28, PSM HR 1.67, 95% CI 1.11-2.51; state decile: IPTW HR 1.55, 95% CI 1.26-1.91, PSM HR 2.0, 95% CI 1.33-2.99). CONCLUSION: Living in a disadvantaged neighborhood was independently associated with increased mortality post-TAVR on multivariate and propensity score matched analysis. Further investigations into the role of neighborhood disadvantage are needed to address disparities and improve outcomes post-TAVR.

Association between mid-term worsening renal function and mortality after transcatheter aortic valve replacement in patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD), acute kidney injury (AKI) and worsening renal function at 30 days after transcatheter aortic valve replacement (TAVR) portend poor outcomes. We sought to evaluate the association between worsening renal function at 3-6 months and mortality among patients with baseline renal dysfunction undergoing TAVR. METHODS: This is a retrospective study of patients with glomerular filtration rate (GFR) < 60 ml/min undergoing TAVR between June 2011 and March 2019 at the Regional Cardiac Catheterization Lab at Kaiser Permanente Los Angeles. Worsening renal function at 3-6 months post-TAVR was defined as: increase in serum creatinine >1.5 times compared to baseline, absolute increase of ≥0.3 mg/dl, or initiation of dialysis. RESULTS: Of 683 patients reviewed, 176 were included in the analysis (median age 84 [IQR 79-88] years, 56% female). Of these, 27 (15.3%) had worsening renal function. AKI post-TAVR (OR 2.9, 95% CI 1.1-7.4, p = .03) and transfusion of ≥4 units red blood cells (OR 8.4, 95% CI 1.2-59, p = .03) were independent predictors of worsening renal function. Worsening renal function increased risk for mortality (HR 2.2, 95% CI 1.17-4.27, p = .015) at a median follow-up of 691 days. Those with improved/stable function with baseline GFR < 60 ml/min had comparable mortality risk to those with baseline GFR ≥ 60 ml/min (18% vs. 16.5%; HR 1.1, 95% CI 0.72-1.75, p = .62). CONCLUSION: Among patients with baseline renal dysfunction, only 15% developed worsening renal function at 3-6 months after TAVR, which was associated with increased mortality. Predictors for worsening renal function include AKI and blood transfusions. Preventative measures peri-procedurally and continued monitoring post-discharge are warranted to improve outcomes.

Predictors of conduction recovery after permanent pacemaker implantation following transcatheter aortic valve replacement.

PURPOSE: Conduction disturbances after transcatheter aortic valve replacement (TAVR) requiring pacemaker (PPM) implantation are a known complication and may be reversible. Therefore, we sought to evaluate the incidence and predictors for atrioventricular (AV) conduction recovery after TAVR. METHODS: A single-center, retrospective study of patients undergoing PPM implantation for conduction disorders after TAVR between June 2011 and March 2019. Conduction recovery was defined as ≤ 1% ventricular pacing (VP) on follow-up PPM interrogation. RESULTS: A total of 110 patients (mean age 83.6 ± 6.6 years, 46.8% female) were included. At a median follow-up of 438 days (interquartile range [IQR] 111-760 days), 35 patients (32%) had conduction recovery, with 50% of these occurring within the first 6 months. On multivariate analysis, predictors of conduction recovery include female sex (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.01-6.4, p = 0.048), non-VP/non-complete heart block rhythm immediately post-TAVR (HR 5.2, 95% CI 1.5-18.1, p = 0.011), normal sinus rhythm 7 days post-TAVR (HR 3.9, 95% CI 1.7-9.2, p = 0.002), and smaller valve size (mm) (HR 0.81, 95% CI 0.7-0.996, p = 0.045). Significant narrowing of the QRS and resolution of new-onset left bundle branch block within 1 month post-TAVR occurred in those with conduction recovery on PPM interrogation. CONCLUSIONS: One-third of patients receiving new PPM implantation have conduction recovery after TAVR, with 50% occurring within the first 6 months. Patient gender, valve size, and rhythm on serial ECGs after TAVR can help identify patients that may recover AV conduction. A conservative approach rather than immediate PPM implantation may be considered in these patients.

Trends in statin utilization among adults with severe peripheral artery disease including critical limb ischemia in an integrated healthcare delivery system.

Evidence suggests that statin therapy in patients with peripheral artery disease (PAD) is beneficial yet use remains suboptimal. We examined trends in statin use, intensity, and discontinuation among adults aged ⩾ 40 years with incident severe PAD and a subset with critical limb ischemia (CLI) between 2002 and 2015 within an integrated healthcare delivery system. Discontinuation of statin therapy was defined as the first 90-day gap in treatment within 1 year following PAD diagnosis. We identified 11,059 patients with incident severe PAD: 31.1% (n = 3442) with CLI and 68.9% (n = 7617) without CLI. Mean (SD) age was 68.6 (11.3) years, 60.5% were male, 54.2% white, 23.2% Hispanic, and 16.2% black. Statin use in the year before diagnosis increased from 50.4% in 2002 to 66.0% in 2015 (CLI: 43.7% to 68.0%; without CLI: 53.1% to 64.2%, respectively). The proportion of patients on high-intensity statins increased from 7.3% in 2002 to 41.9% in 2015 (CLI: 7.2% to 39.4%; without CLI: 7.4% to 44.2%, respectively). Of the 40.5% (n = 4481) who were not on a statin in the year before diagnosis, 13.5% (n = 607) newly initiated therapy within 1 month (CLI: 10.1% (n = 150); without CLI: 15.3% (n = 457)). Following diagnosis, 12.5% (n = 660) discontinued statin therapy within 1 year (CLI: 15.5% (n = 202); without CLI: 11.5% (n = 458)). Although use of statins increased from 2002 to 2015, a substantial proportion of the overall PAD and CLI subpopulation remained untreated with statins, representing a significant treatment gap in a population at high risk for cardiovascular events and adverse limb outcomes.

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography.

OBJECTIVES: The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI. BACKGROUND: CI-AKI is a common complication of percutaneous coronary procedures, associated with increased morbidity and mortality. The AVERT system alters the coronary injection pressure profile by diverting contrast away from the patient during coronary injection. METHODS: The AVERT trial was a prospective, multicenter, 1:1 randomized clinical trial in 578 subjects with either baseline estimated glomerular filtration rate 20 to 30 ml/min/1.73 m2 or estimated glomerular filtration rate 30 to 60 ml/min/1.73 m2 and at least 2 additional risk factors for CI-AKI. Patients undergoing coronary angiography with planned or possible percutaneous coronary intervention (PCI) were randomized to hydration plus the AVERT system (n = 292) or hydration only (n = 286). The primary effectiveness endpoints were: 1) the total CMV used; and 2) the incidence of CI-AKI, defined as a ≥0.3 mg/dl increase in serum creatinine within 5 days post-procedure. RESULTS: Patient demographics were well balanced between the groups, with mean baseline serum creatinine of 1.6 ± 0.4 mg/dl and 64.9% patients with diabetes mellitus. PCI was performed in 42.2% of procedures, with coronary angiography in the remainder. Use of AVERT resulted in a 15.5% relative reduction in CMV overall (85.6 ± 50.5 ml vs. 101.3 ± 71.1 ml; p = 0.02) and a 22.8% relative reduction in CMV among PCI patients (114 ± 55 ml vs. 147 ± 81 ml; p = 0.001). The maximum relative reduction in CMV was 46% (124 ± 48 ml vs. 232 ± 97 ml; p = 0.01) when ≥3 lesions were treated. There were no differences in the rates of CI-AKI (27.0% vs. 26.6%; p = 0.70) between the study groups. CONCLUSIONS: Use of the AVERT system was feasible and safe, with acceptable image quality during coronary angiography and PCI. AVERT significantly reduced CMV, with the extent of CMV reduction correlating with procedural complexity. No significant differences in CI-AKI were observed with AVERT in this trial. (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN [AVERT]; NCT01976299).

Open Versus Endovascular or Hybrid Thoracic Aortic Aneurysm Repair.

Thoracic aortic aneurysms are associated with significant morbidity and mortality. There are multiple underlying etiologies, including genetic abnormalities, that have important implications in their natural history. The variable histologic, anatomic, and clinical presentations necessitate careful consideration of available treatment options. Surgical repair of these aneurysms has been the mainstay of treatment; however, these approaches can carry a relatively high risk of morbidity and mortality. Endovascular approaches have now become first-line therapy for descending thoracic aneurysms, and with advancements in graft technology, endovascular approaches are being increasingly employed for hybrid repairs of the aortic arch and even the ascending aorta. However, to date, clinical outcomes from randomized trials and long-term follow-up are limited. As technology continues to advance, there is the potential for further integration of surgical and endovascular treatments so that patients have the best opportunity for a favorable outcome.

Multi-Center, Community-Based Cardiac Implantable Electronic Devices Registry: Population, Device Utilization, and Outcomes.

BACKGROUND: The purpose of this study is to describe key elements, clinical outcomes, and potential uses of the Kaiser Permanente-Cardiac Device Registry. METHODS AND RESULTS: This is a cohort study of implantable cardioverter defibrillators (ICD), pacemakers (PM), and cardiac resynchronization therapy (CRT) devices implanted between January 1, 2007 and December 31, 2013 by ≈400 physicians in 6 US geographical regions. Registry data variables, including patient characteristics, comorbidities, indication for procedures, complications, and revisions, were captured using the healthcare system's electronic medical record. Outcomes were identified using electronic screening algorithms and adjudicated via chart review. There were 11 924 ICDs, 33 519 PMs, 4472 CRTs, and 66 067 leads registered. A higher proportion of devices were implanted in males: 75.1% (ICD), 55.0% (PM), and 66.7% (CRT), with mean patient age 63.2 years (ICD), 75.2 (PM), and 67.2 (CRT). The 30-day postoperative incidence of tamponade, hematoma, and pneumothorax were ≤0.3% (ICD), ≤0.6% (PM), and ≤0.4% (CRT). Device failures requiring revision occurred at a rate of 2.17% for ICDs, 0.85% for PMs, and 4.93% for CRTs, per 100 patient observation years. Superficial infection rates were <0.03% for all devices; deep infection rates were 0.6% (ICD), 0.5% (PM), and 1.0% (CRT). Results were used to monitor vendor-specific variations and were systematically shared with individual regions to address potential variations in outcomes, utilization, and to assist with the management of device recalls. CONCLUSIONS: The Kaiser Permanente-Cardiac Device Registry is a robust tool to monitor postprocedural patient outcomes and postmarket surveillance of implants and potentially change practice patterns.

Cardiovascular Disease Risk Profiles in Survivors of Adolescent and Young Adult (AYA) Cancer: The Kaiser Permanente AYA Cancer Survivors Study.

PURPOSE: To describe the epidemiology and risk factors for cardiovascular disease (CVD) in survivors of adolescent and young adult (AYA) cancer. METHODS: We identified a retrospective cohort of 2-year survivors of AYA cancer who were diagnosed between the ages of 15 to 39 years (1998 to 2009) at Kaiser Permanente Southern California. A comparison group without cancer was selected and matched 10:1 to cancer survivors on the basis of age, sex, Kaiser Permanente Southern California membership, and calendar year. Patients were followed through December 31, 2012, for coronary artery disease, heart failure, and stroke. Time-dependent Poisson regression was used to evaluate the effect that cancer survivorship had on the risk of developing CVD, adjusted for cardiovascular risk factors (CVRFs; ie, diabetes, hypertension, and dyslipidemia), ethnicity, smoking, and overweight/obesity. Among cancer survivors, mortality risk by CVD status was examined using Cox regression. RESULTS: A total of 5,673 2-year survivors of AYA cancer and 57,617 comparison patients were included, representing 24,839 and 239,073 person-years of follow-up, respectively. Overall, cancer survivors had more than two-fold risk of developing CVD (adjusted incidence rate ratio, 2.37; 95% CI, 1.93 to 2.93) when compared with patients without cancer; survivors of leukemia and breast cancer were at the highest risk (adjusted incidence rate ratio, 4.23; 95% CI, 1.73 to 10.31; and 3.63; 95% CI, 2.41 to 5.47, respectively) of developing CVD. Having any of the CVRFs increased the risk of CVD in cancer survivors. Cancer survivors who developed CVD had an 11-fold increased overall mortality risk (hazard ratio, 10.9; 95% CI, 8.1 to 14.8) when compared with survivors without CVD. CONCLUSION: Survivors of AYA cancer are at increased risk for developing CVD. Survival after CVD onset is compromised, and CVRFs are independent modifiers of CVD risk. These data form the basis for identifying high-risk individuals and proactive management of CVRFs.

Statin use prior to angiography for the prevention of contrast-induced acute kidney injury: a meta-analysis of 19 randomised trials.

AIMS: A systematic review and a meta-analysis were performed to define better the role of statin use prior to angiography in preventing contrast-induced acute kidney injury (CI-AKI). METHODS AND RESULTS: MEDLINE, Embase, Cochrane Library, references from review articles, and conference proceedings were searched, with no language restriction, for randomised controlled trials (RCT) evaluating the use of statin therapy prior to angiography for the prevention of CI-AKI. Nineteen RCTs including 7,161 patients were identified. The pooled analysis demonstrated a significant reduction in the incidence of CI-AKI in patients treated with statin prior to invasive angiography when compared with control (RR 0.52; 95% CI: 0.40-0.67). Patients with chronic kidney disease stage 3 or worse were largely underrepresented in these trials, and statin therapy did not significantly reduce the risk of CI-AKI in the three studies which enrolled a patient population with a mean eGFR of <60 ml/min (RR 0.54; 95% CI: 0.2-1.42). CONCLUSIONS: This meta-analysis suggests a potential benefit for statin use prior to angiography to reduce the incidence of CI-AKI. Additional research is needed to define better the benefits of statin therapy prior to angiography to prevent CI-AKI, especially in high-risk patients with chronic kidney disease who were largely underrepresented in the available trials.

Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial.

BACKGROUND: The administration of intravenous fluid remains the cornerstone treatment for the prevention of contrast-induced acute kidney injury. However, no well-defined protocols exist to guide fluid administration in this treatment. We aimed to establish the efficacy of a new fluid protocol to prevent contrast-induced acute kidney injury. METHODS: In this randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, we assessed the efficacy of a new fluid protocol based on the left ventricular end-diastolic pressure for the prevention of contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. The primary outcome was the occurrence of contrast-induced acute kidney injury, which was defined as a greater than 25% or greater than 0·5 mg/dL increase in serum creatinine concentration. Between Oct 10, 2010, and July 17, 2012, 396 patients aged 18 years or older undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min per 1·73 m(2) or less and one or more of several risk factors (diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years) were randomly allocated in a 1:1 ratio to left ventricular end-diastolic pressure-guided volume expansion (n=196) or the control group (n=200) who received a standard fluid administration protocol. Four computer-generated concealed randomisation schedules, each with permuted block sizes of 4, were used for randomisation, and participants were allocated to the next sequential randomisation number by sealed opaque envelopes. Patients and laboratory personnel were masked to treatment assignment, but the physicians who did the procedures were not masked. Both groups received intravenous 0·9% sodium chloride at 3 mL/kg for 1 h before cardiac catheterisation. Analyses were by intention to treat. Adverse events were assessed at 30 days and 6 months and all such events were classified by staff who were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01218828. FINDINGS: Contrast-induced acute kidney injury occurred less frequently in patients in the left ventricular end-diastolic pressure-guided group (6·7% [12/178]) than in the control group (16·3% [28/172]; relative risk 0·41, 95% CI 0·22-0·79; p=0·005). Hydration treatment was terminated prematurely because of shortness of breath in three patients in each group. INTERPRETATION: Left ventricular end-diastolic pressure-guided fluid administration seems to be safe and effective in preventing contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. FUNDING: Kaiser Permanente Southern California regional research committee grant.

Effects of physical activity and sedentary time on the risk of heart failure.

BACKGROUND: Although the benefits of physical activity for risk of coronary heart disease are well established, less is known about its effects on heart failure (HF). The risk of prolonged sedentary behavior on HF is unknown. METHODS AND RESULTS: The study cohort included 82 695 men aged≥45 years from the California Men's Health Study without prevalent HF who were followed up for 10 years. Physical activity, sedentary time, and behavioral covariates were obtained from questionnaires, and clinical covariates were determined from electronic medical records. Incident HF was identified through International Classification of Diseases, Ninth Revision codes recorded in electronic records. During a mean follow-up of 7.8 years (646 989 person-years), 3473 men were diagnosed with HF. Controlling for sedentary time, sociodemographics, hypertension, diabetes mellitus, unfavorable lipid levels, body mass index, smoking, and diet, the hazard ratio (95% confidence interval [CI]) of HF in the lowest physical activity category compared with those in the highest category was 1.52 (95% CI, 1.39-1.68). Those in the medium physical activity category were also at increased risk (hazard ratio, 1.17 [95% CI, 1.06-1.29]). Controlling for the same covariates and physical activity, the hazard ratio (95% CI) of HF in the highest sedentary category compared with the lowest was 1.34 (95% CI, 1.21-1.48). Medium sedentary time also conveyed risk (hazard ratio, 1.13 [95% CI, 1.04-1.24]). Results showed similar trends across white and Hispanic subgroups, body mass index categories, baseline hypertension status, and prevalent coronary heart disease. CONCLUSIONS: Both physical activity and sedentary time may be appropriate intervention targets for preventing HF.

Discontinuation of long-term clopidogrel therapy is associated with death and myocardial infarction after saphenous vein graft percutaneous coronary intervention.

OBJECTIVES: This study sought to examine the pattern of death and myocardial infarction (MI) after clopidogrel cessation in patients undergoing percutaneous coronary intervention (PCI) of the saphenous vein graft (SVG). BACKGROUND: The timing and incidence of adverse events by different durations of clopidogrel therapy after SVG PCI remain unknown. METHODS: This is a cohort study of patients undergoing SVG PCI between 2000 and 2009, followed for all-cause mortality or MI after stopping clopidogrel. Incidence rates were calculated across different time periods after clopidogrel cessation. Adjusted incidence rate ratios (IRR) were calculated with multivariable regression (piecewise exponential and Poisson). RESULTS: There were 603 patients who underwent SVG PCI, of which 411 were event-free at the time of clopidogrel cessation. The incidence rate (95% confidence interval: [CI])/1,000 person-days of death or MI after stopping clopidogrel in the time intervals of 0 to 90 days, 91 to 365 days, and 1 to 2 years were 1.26 (95% CI: 0.93 to 1.70), 0.41 (95% CI: 0.30 to 0.56), and 0.41 (95% CI: 0.30 to 0.55), respectively. In multivariable analyses, the overall IRR (95% CI) for death or MI in the 0- to 90-day interval after stopping clopidogrel compared with the 91- to 365-day interval was 2.58 (95% CI: 1.64 to 4.07). Similar results were observed over a broad range of clopidogrel treatment durations (<6 months, 6 months to 1 year, 1 to 2 years, or >2 years). The results were also consistent across subgroups, including sex, stent type, stent diameter, PCI period, and diabetes status. When death alone was evaluated, there remained a significant increase in the event rate in the 0- to 90-day interval compared with the 91- to 365-day interval (IRR: 2.33; 95% CI: 1.32 to 4.11). CONCLUSIONS: A clustering of events was observed in the initial 0 to 90 days after clopidogrel cessation in all treatment durations of clopidogrel investigated after SVG PCI. These results might have important implications in high-risk cohorts undergoing PCI. Additional studies are needed to elucidate the mechanisms underlying the early clustering of events after clopidogrel cessation.