Randomised trial of the comparison of drug-eluting stents in patients with diabetes: OCT DES trial.

Background: To date, there have been limited comparisons performed between everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in patients with diabetes mellitus (DM). The objectives of this study was to assess the use of second-generation drug-eluting stents in patients with DM, using optical coherence tomography (OCT) to compare the level of stent coverage of Boston Scientific Promus Element EES compared with Medtronic Resolute Integrity ZES.(Clinicaltrials.gov number NCT02060357). Methods: This is a single-centre randomised blinded trials assessing two commercially available stents in 60 patients with diabetes (ZES: n=30, EES: n=30). Patients underwent intracoronary assessment at 6 months with OCT assessing stent coverage, malapposition, neointimal thickness and percentage of in-stent restenosis (ISR). Results: Of the 60 patients randomised, 46 patients underwent OCT analysis. There was no difference in baseline characteristics between the two groups. Both Promus Element and Resolute Integrity had low rates of uncovered struts at 6 months with no significant difference between the two groups (2.44% vs 1.24%, respectively; P=0.17). Rates of malapposition struts (3.9% vs 2.5%, P=0.25) and percentage of luminal loss did not differ between stent types. In addition, there was no significant difference in major adverse cardiovascular events (P=0.24) between the stent types. Conclusions: This study is the first randomised trial to evaluate OCT at 6 months for ZES and EES in patients with diabetes. Both stents showed comparable strut coverage at 6 months, with no difference in ISR rates at 6 months.

Remote ischemic preconditioning has a neutral effect on the incidence of kidney injury after coronary artery bypass graft surgery.

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60 ml/min per 1.73 m(2)) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24 h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48 h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD.

Impact of diabetes mellitus and renal insufficiency on 5-year mortality following coronary artery bypass graft surgery: a cohort study of 4869 UK patients.

OBJECTIVES: Diabetes mellitus (DM) and renal impairment (RI) are both independent predictors of mortality after coronary artery bypass graft surgery (CABG). The two conditions often coexist, yet the impact on long-term prognosis after CABG of each factor relative to the other and the two in combination is uncertain. METHODS: We undertook a prospective cohort study of 4869 patients who underwent CABG between 2003 and 2007. The cohort was divided into four groups according to preoperative diabetic status and renal function: patients without either DM or RI (reference group), patients with DM alone, patients with RI alone and patients with both DM and RI. Clinical outcomes were compared between groups. Patients receiving renal replacement therapy were excluded. The primary outcome was 5-year all-cause mortality. RESULTS: The crude 5-year all-cause mortality rate was 9.0% for patients in the reference group, 11.1% for patients with DM alone, 20.3% for patients with RI alone and 28.5% for patients with both DM and RI (P < 0.0001). Five-year survival adjusted for potential confounding factors was significantly worse for patients with DM (hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.06-1.59), patients with RI (HR 1.32; 95% CI 1.08-1.61) and patients with both DM and RI (HR 2.04; 95% CI 1.65-2.53) when compared with patients with neither condition. CONCLUSIONS: Preoperative DM and RI were important predictors of 5-year mortality after CABG. Patients with RI alone had a higher mortality rate than patients with DM alone, but this difference was largely accounted for by age and other comorbidities. The combination of DM and RI doubled the 5-year mortality rate after CABG independently of potential confounding factors.

The impact of acute kidney injury on midterm outcomes after coronary artery bypass graft surgery: a matched propensity score analysis.

BACKGROUND: The development of acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery is associated with increased short- and long-term mortality. Whether AKI has a causal relationship with subsequent mortality or whether the development of AKI simply occurs in patients with more comorbidity undergoing more complex procedures remains unresolved. METHODS AND RESULTS: This was an observational cohort study of prospectively collected data from 4694 patients discharged from the hospital after first-time CABG surgery at a tertiary cardiac center between 2003 and 2008. AKI was defined using the Risk, Injury, Failure, Loss, and End stage (RIFLE) criteria, which require at least a 50% increase in serum creatinine. The primary outcome measure was all-cause mortality determined via UK Office of National Statistics. A total of 562 (12.0%) of patients developed AKI after CABG surgery. Patients who developed AKI were older, more likely to be female, and had more comorbidity than patients who did not develop AKI. In a Cox multivariable analysis, the development of AKI was an independent predictor of midterm mortality (hazard ratio, 1.80; 95% confidence interval, 1.50-2.16). Subsequently, a comparison of 562 patients who sustained AKI with 562 propensity score-matched patients who did not sustain AKI was undertaken. After propensity matching, baseline clinical and operative characteristics were similar between both groups. After Cox multivariable analysis of the propensity-matched cohort, AKI remained an independent predictor of midterm mortality (hazard ratio, 1.52; 95% confidence interval, 1.19-1.93). CONCLUSIONS: The development of AKI after CABG is a serious event associated with worse midterm survival. This excess mortality cannot be explained simply by coexisting comorbidity and surgical complexity.

Prognostic impact of anaemia on patients with ST-elevation myocardial infarction treated by primary PCI.

AIM: The aim of this study was to investigate the effects of baseline anaemia on the outcome in patients treated by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. METHODS: This study was a retrospective cohort study of 2418 patients with ST-elevation myocardial infarction treated by PPCI between January 2004 and August 2010 at a single centre. We investigated the outcome in patients with anaemia compared with that in patients with a normal haemoglobin (Hb) level. Anaemia was defined according to the WHO definition as an Hb level less than 12 g/dl for female individuals and less than 13 g/dl for male individuals. We also calculated hazard ratios using a stratified model according to the Hb level. RESULTS: A total of 471 (19%) patients were anaemic at presentation. The anaemic cohort was older (72.2 vs. 62.4 years, P<0.0001) and had a higher incidence of diabetes (28 vs. 16%, P<0.0001), hypertension (57 vs. 43%, P=0.01), hypercholesterolaemia (48 vs. 40%, P=0.007), previous PCI (15 vs. 9%, P<0.0001), previous myocardial infarction (23 vs. 12%, P=0.002), and cardiogenic shock (12 vs. 5%, P<0.0001). Over a mean follow-up period of 3 years there was significantly higher all-cause mortality in the anaemic group compared with the normal Hb group (20.4 vs. 13.5%, P<0.0001). However, after adjustment for all variables using multivariate analysis, anaemia (on the basis of the WHO definitions) was found not to be an independent predictor of mortality or major adverse cardiac events over the follow-up period. Further, when we used a model stratified by g/dl, we found that there was an increased risk for adverse outcomes among men with low Hb levels. There appeared to be a threshold value of Hb (13 g/dl) associated with increased risk. Although a similar trend was observed among women, no significant difference was observed. CONCLUSION: Patients with anaemia undergoing PPCI are at a higher risk of an adverse outcome. Anaemia is a simple and powerful marker of poor prognosis. Although anaemia (based on the WHO definitions) does not appear to be an independent predictor of all-cause mortality or major adverse cardiac events after PPCI on multivariate analysis, there appears to be a threshold value of Hb among men, below which there is an associated increased risk for PPCI.

Contemporary analysis of incidence and outcomes of stent thrombosis presenting as ST elevation myocardial infarction in a primary percutaneous coronary intervention cohort.

There are limited data about the effectiveness of primary percutaneous coronary intervention (PPCI) for stent thrombosis treatment. We aimed to evaluate the prevalence and outcomes of PPCI in patients with ST elevation acute myocardial infarction (STEMI) due to stent thrombosis, and comparing the outcomes with patients treated for de novo coronary thrombosis. This was an observational cohort study of 2,935 patients who underwent PPCI from 2003 to 2011 with follow-up for a median of 3.0 years (interquartile range 1.2 to 4.6). The primary end point was the first major adverse cardiac event (MACE) defined as death, nonfatal myocardial infarction, stroke, or target vessel revascularization. Stent thrombosis overall accounted for 6.6% (194 of 2,935) of all STEMIs with a proportion that increased over time (3.3% in 2004 to 9.4% in 2011). A total of 34.5% were early, 30.9% late stent thrombosis, and 34.5% were very late stent thrombosis. Indications for the original intervention were elective in 27.8%, after acute coronary syndrome (non-STEMI or unstable angina) in 21.1%, and after PPCI in 51.1%. Patients with stent thrombosis had higher rates of hypertension, hypercholesterolemia, diabetes, renal dysfunction, and previous myocardial infarction or coronary artery bypass surgery compared with patients with native artery occlusion. MACE rates were higher in patients with stent thrombosis compared with patients with native artery occlusions (40.9%, 95% confidence interval [CI] 31.1 to 50.6 vs 15.1%, 95% CI 12.5 to 18.3; p <0.0001). The poor outcome of stent thrombosis was particularly associated with early and late stent thromboses. Very late stent thrombosis appears to be a relatively less serious event, with similar outcomes to native vessel thromboses (MACE very late stent thrombosis 16.5%, 95% CI 8.2 to 28.6 vs native 15.1%, 95% CI 12.5 to 18.3, p = 0.245). In conclusion, stent thrombosis accounts for an increasing proportion of STEMI and is associated with worse outcomes compared with native artery occlusion.

Safety and feasibility of hospital discharge 2 days following primary percutaneous intervention for ST-segment elevation myocardial infarction.

AIM: Primary percutaneous coronary intervention (PPCI) produces more effective coronary reperfusion and allows immediate risk stratification compared with fibrinolysis. We investigated the safety and feasibility of very early discharge at 2 days following PPCI in selected low-risk cases. METHODS: This was a prospective observational cohort study of 2779 patients who underwent PPCI between 2004 and 2011. Patients meeting the following criteria were deemed suitable for very early discharge; TIMI III flow, left ventricle (LF) ejection fraction >40%, and rhythmic and haemodynamic stability out to 48 h. Higher-risk patients who did not fulfil these criteria were discharged later according to physician preference. All patients were offered outpatient review by a multidisciplinary team. Endpoints included 30 day readmission rates and major adverse cardiac events (MACE) out to a median of 2.8 years (IQR range: 1.3-4.4 years). RESULTS: 1309 (49.3%) PPCI patients met very early discharge criteria, of whom 1117 (85.3%) were actually discharged at 2 days. 620 (23.4%) were discharged at 3 days, and 916 (34.5%) >3 days after admission (median 5, IQR: 4-8) days). Patients discharged at 2 days were younger, and had lower rates of diabetes, renal dysfunction, multivessel coronary artery disease, previous myocardial infarction, and previous coronary artery bypass surgery, compared with patients discharged later. 30-day readmission rates for non-MACE events were 4.8%, 4.9% and 4.6% for patients discharged 2 days, 3 days and >3 days after admission, respectively. MACE rates were lowest in patients discharged at 2 days (9.6%, 95% CI 4.7% to 16.6%) compared with patients discharged at 3 days (12.3% 95% CI 6.0% to 19.2%) and >3 days (28.6% 95% CI 22.9% to 34.7%, p<0.0001) after admission. CONCLUSIONS: Our data suggest that discharge of low-risk patients 2 days after successful PPCI is feasible and safe. Over 40% of all patients with ST-elevation myocardial infarction may be suitable for early discharge with important implications for healthcare costs.

Successful recanalization of chronic total occlusions is associated with improved long-term survival.

OBJECTIVES: This study investigated the impact of procedural success on mortality following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in a large cohort of patients in the drug-eluting stent era. BACKGROUND: Despite advances in expertise and technologies, many patients with CTO are not offered PCI. METHODS: A total of 6,996 patients underwent elective PCI for stable angina at a single center (2003 to 2010), 836 (11.9%) for CTO. All-cause mortality was obtained to 5 years (median: 3.8 years; interquartile range: 2.0 to 5.4 years) and stratified according to successful chronic total occlusion (sCTO) or unsuccessful chronic total occlusion (uCTO) recanalization. Major adverse cardiac events (MACE) included myocardial infarction (MI), urgent revascularization, stroke, or death. RESULTS: A total of 582 (69.6%) procedures were successful. Stents were implanted in 97.0% of successful procedures (mean: 2.3 ± 0.1 stents per patient, 73% drug-eluting). Prior revascularization was more frequent among uCTO patients: coronary artery bypass grafting (CABG) (16.5% vs. 7.4%; p < 0.0001), PCI (36.0% vs. 21.2%; p < 0.0001). Baseline characteristics were otherwise similar. Intraprocedural complications, including coronary dissection, were more frequent in unsuccessful cases (20.5% vs. 4.9%; p < 0.0001), but did not affect in-hospital MACE (3% vs. 2.1%; p = NS). All-cause mortality was 17.2% for uCTO and 4.5% for sCTO at 5 years (p < 0.0001). The need for CABG was reduced following sCTO (3.1% vs. 22.1%; p < 0.0001). Multivariate analysis demonstrated that procedural success was independently predictive of mortality (hazard ratio [HR]: 0.32 [95% confidence interval (CI): 0.18 to 0.58]), which persisted when incorporating a propensity score (HR: 0.28 [95% CI: 0.15 to 0.52]). CONCLUSIONS: Successful CTO PCI is associated with improved survival out to 5 years. Adoption of techniques and technologies to improve procedural success may have an impact on prognosis.

Myocardial function may improve equally in diabetic patients following both multivessel percutaneous coronary intervention and coronary artery bypass grafting: results from a CARDia trial substudy.

AIMS: The CARDia (Coronary Artery Revascularization in Diabetes) trial compared coronary artery bypass grafting (CABG) and optimal percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary disease. Patients enrolled had symptoms of myocardial ischaemia. As symptom assessment is flawed in diabetic patients, a substudy was undertaken to compare the extent to which these revascularization strategies alter reversible ischaemia. METHODS AND RESULTS: Seventy-one patients underwent stress echo at baseline and at 6 months. A 17-segment echocardiographic wall motion score index (WMSI) was assigned at baseline [WMSI(pre)] and at 6 months [WMSI(post)]. An overall score defined the difference: WMSI(∂) = WMSI(pre)--WMSI(post). Of 71 patients recruited, 42 underwent PCI and 29 CABG. Mean WMSI(pre) in the PCI group was 1.63 and mean WMSI(post) was 1.32. Mean WMSI(pre) in the CABG group was 1.69 and mean WMSI(post) was 1.46. The PCI WMSI(∂) was 0.31 and CABG WMSI(∂) was 0.23 (P = 0.8). Of 42 PCI patients, 39 demonstrated ischaemia at baseline. At 6 months 31 had improvements in ischaemia (79%), 5 showed no improvement, and 3 ischaemia worsened. Of 29 CABG patients, 23 demonstrated ischaemia at baseline. At 6 months, 20 had improvements in ischaemia (87%), 2 had no improvement, and in 1 ischaemia worsened. No difference was seen in the number of patients with improvements in reversible ischaemia between PCI and CABG [79 vs. 87%, (P = 0.9)]. CONCLUSION: Optimal revascularization in diabetic patients with multivessel disease remains controversial. This subset analysis of the CARDia trial suggests both PCI and CABG achieve similar improvement in reversible ischaemia.

Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial.

OBJECTIVES: The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and symptomatic multivessel coronary artery disease. BACKGROUND: CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization. METHODS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available. RESULTS: At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio [HR]: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively. CONCLUSIONS: The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).

The Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes Study: 5-year follow-up of revascularization with percutaneous coronary intervention versus coronary artery bypass grafting in diabetic patients with multivessel disease.

OBJECTIVES: The aim of the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study was to assess percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) as treatments for multivessel coronary artery disease in diabetic patients. BACKGROUND: CABG is generally regarded as the treatment of choice for multivessel coronary artery disease in diabetes. PCI is an alternative therapy. The Bypass Angioplasty Revascularization in Type 1 and 2 Diabetes study compared long-term outcomes of CABG with PCI in diabetic patients treated during the bare-metal stent era. METHODS: We collected data prospectively on consecutive diabetic patients undergoing index angiography in a single tertiary centre from January 1998 to December 2001. Multivessel coronary artery disease was defined as more than 50% luminal stenosis in two or more vessels. Exclusion criteria included left main stem disease and previous revascularization. RESULTS: Two hundred and thirty-five eligible patients underwent CABG and 237 PCI. Median follow-up was 5.4 years. There were 46 (19%) deaths in the CABG group and 43 (18%) deaths in the PCI group (P = 0.64). Cox regression analysis revealed baseline glomerular filtration rate (hazard ratio 0.979, P = 0.001), age (hazard ratio 1.034, P = 0.033), urgent procedure (hazard ratio 1.97, P = 0.008) and myocardial infarction within 4 weeks (hazard ratio 2.494, P = 0.041) to be important predictors of outcome. At 5 years, there was no mortality difference (hazard ratio 1.0) following adjustment for baseline characteristics, and the Kaplan-Meier survival curves were similar. A subanalysis of patients with three-vessel disease revealed similar outcomes with both PCI and CABG. CONCLUSION: In the Bypass Angioplasty Revascularization in Type 1 and Type 2 Diabetes study, diabetic patients with multivessel coronary artery disease had similar long-term mortality whether treated with CABG or PCI, the revascularization determined by the physician's choice. This was despite the frequent use of a strategy of selective revascularization in the PCI arm. Randomized trials comparing PCI and CABG specifically in diabetes, that is, Coronary Artery Revascularization in Diabetes and Future Revascularization Evaluation in Diabetes Mellitus: Optimal Management, will show whether drug-eluting stents further enhance PCI outcomes over the long term.

Limited clinical utility of Holter monitoring in patients with palpitations or altered consciousness: analysis of 8973 recordings in 7394 patients.

AIMS: To determine the clinical utility of 24 hour Holter monitoring by measuring the frequency of candidate arrhythmias recorded during the investigation of palpitations and altered consciousness. METHODS: Of 9,729 Holter recordings, reports were available in 8,973 (92.2%) performed in the 7394 patients who comprise the study group. The mean age of the study group was 66 +/- 19 years and 56.4% were women. RESULTS: The most common indications were altered consciousness (41.7%) and palpitations (36.2%). Among patients with palpitations and sinus rhythm (n=2688), recordings were normal in 2247 (83.6%). Abnormalities included paroxysmal atrial fibrillation (PAF, 6.6%), narrow complex tachycardia (NCT, 2.8%) nonsustained or sustained ventricular tachycardia (NSVT/VT, 2.6%). Among patients with altered consciousness (n=3075), recordings were normal in 2589 (84.2%). Abnormalities included PAF (9.5%), NCT (2.6%), NSV/VT (0.2%), pause >2.8s (2.2%) and high degree AV block (1.3%). The diagnostic yield of Holter monitoring was particularly low in patients aged < or =50 years, of whom 93.1% had palpitations and 95.3% had altered consciousness had normal recordings. CONCLUSIONS: The diagnostic utility of Holter monitoring in patients being investigated for palpitations and altered consciousness is very limited, particularly in young patients for whom alternative diagnostic methods should be considered.

Has anything changed in multivessel coronary artery revascularization in diabetes since BARI?

Diabetic patients have an increased risk of coronary disease partly due to a higher frequency of associated risk factors including hypertension and hyperlipidemia but also from specific risks largely resulting from insulin resistance, hyperinsulinemia and hyperglycemia. This has resulted in a greater need for revascularization. Despite this there are few randomized data comparing surgery and angioplasty in patients with diabetes. The evidence to define the best operative strategy is limited, mainly confined to a subanalysis of the BARI trial suggesting the superiority of surgery in patients with multivessel disease. However there has been in Europe a wide increase in multivessel angioplasty, even in diabetic patients. This article discusses the higher risk of patients with diabetes, the data comparing surgery and angioplasty and outlines the advances in angioplasty since BARI.

A comparison of three radionuclide myocardial perfusion tracers in clinical practice: the ROBUST study.

UNLABELLED: There are no large studies available to guide the selection of thallium (Tl), methoxyisobutylisonitrile (MIBI) or tetrofosmin (Tf) for myocardial perfusion imaging. Our objective was to compare the technical and clinical performance of the three in routine clinical practice. We randomised 2,560 patients to receive Tl, MIBI or Tf. A 1-day stress/rest protocol was used for MIBI and Tf. Tracer uptake was scored using a 17-segment model, quality and artefact scores were assigned, and ratios of heart (H), liver (L), subdiaphragmatic (S) and lung activity were measured. Mean quality scores (stress/rest) were Tl 2.13/2.16, MIBI 2.18/2.39, Tf 2.18/2.42 ( P=ns stress and <0.00001 rest). For attenuation artefact, Tl>MIBI=Tf ( P<0.05) and for low-count artefact Tl>MIBI>Tf ( P<0.001). For H/S, Tl>MIBI=Tf, for H/L Tl>MIBI=Tf, and for H/lung Tl