Drug-Eluting versus Bare-Metal Stents in Saphenous Vein Grafts Compared to Native Coronary Vessels: The Norwegian Coronary Stent Trial Study.

BACKGROUND: Drug-eluting stents (DES) reduce target lesion revascularization (TLR) with no effect on mortality or myocardial infarction (MI) compared to bare-metal stents (BMS) in native vessels. Randomized stent studies in saphenous vein grafts (SVG) are few and the reported effects are ambiguous. The Norwegian Coronary Stent Trial study is the first to randomize lesions to percutaneous coronary intervention in native vessels and SVG. AIMS: The aim of this study was to compare the rate of mortality, MI, and TLR across stent and vessel types. METHODS: In this substudy, 6,087 patients with a single lesion in native vessels and 164 in SVG were followed for 5 years. RESULTS: MI was more frequent in SVG (subdistributional hazard ratio [SHR] 4.95 (3.75-6.54, p < 0.001), but not affected by stent type. In the first 500 days, DES reduced TLR in native vessels (SHR 0.21 (0.15-0.30) p < 0.001) and SVG (SHR 0.18 (0.04-0.80) p = 0.02). Thereafter, DES and BMS were equivalent in native vessels, but DES had a higher TLR rate than BMS in SVG (SHR 3.31 (1.23-8.94) p = 0.02). After 5 years, the TLR rate was still significantly lower for DES in native vessels (3.2% vs. 7.8%, p < 0.001) but not in SVG (21.4% vs. 18. 4%). CONCLUSION: In SVG, no difference in TLR between DES and BMS was observed after 5 years in contrast to persistent benefit in native vessels. The high rate of TLR and MI in SVG makes treatment of native vessels a preference whenever feasible and better treatment options for SVG are warranted.

Analyses of Increased Mortality in New and Known Diabetes in Patients with Coronary Disease Enrolled in the NORSTENT Randomized Study.

BACKGROUND: NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention with drug-eluting stents (DES) or bare-metal stents (BMS) with a 5-year follow-up. Among the patients, 5,512 had measured either fasting glucose level or percent glycated hemoglobin (HbA1c) at the index procedure. That cohort constitutes the present study population analyzing mortality and evaluating treatment heterogeneity of randomized stent in diabetic versus nondiabetic subgroups. RESULTS: The cohort consisted of 4,174 (75.7%) patients without diabetes, 716 (13.0%) with known diabetes, and 622 (11.3%) with no diabetes in history but elevated fasting glucose level >7.0 mmol/L or HbA1c >6.5% and therefore defined as new diabetes. Patients with known diabetes had a significantly increased all-cause (hazard ratio [HR] 1.99, 95% CI 1.51-2.62, p < 0.001), cardiac (subhazard ratio [SHR] 2.47, 95% CI 1.55-3.93, p < 0.001), and noncardiac (SHR 1.74, 95% CI 1.23-2.44, p = 0.002) mortality after adjustment for baseline variables. In the follow-up of 5 years, patients with new diabetes, however, had a marginally increased all-cause (HR 1.40, 95% CI 1.01-1.93, p = 0.043) and significantly increased noncardiac mortality (SHR 1.52, 95% CI 1.06-2.20, p = 0.025), but no increase in cardiac mortality (SHR 1.06, 95% CI 0.53-2.12, p = 0.86) after the same adjustment. The majority of the mortality was cardiac in the first 1-2 years after intervention; thereafter, noncardiac mortality dominated. However, the time period for when noncardiac mortality became the dominating cause varied considerably and significantly between the groups. There was no heterogeneity in mortality in response to randomized stent between diabetics and nondiabetics. CONCLUSION: Known diabetes has increased cardiac and noncardiac mortality in contrast to new diabetes which is only associated with increased noncardiac mortality during the 5-year follow-up. Diabetic and nondiabetic patients have the same response to the treatment with BMS or DES.

The Effect of Drug-Eluting Stents on Target Lesion Revascularization in Native Coronary Arteries: Results from the NORSTENT Randomized Study.

BACKGROUND: The NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) or bare-metal stent (BMS) with 5-year follow-up. No difference was found in the composite primary outcome of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularizations, which were reduced by DES. We report the occurrence of target lesion revascularization (TLR) in time and across demographic and clinical subgroups in patients with lesions in native coronary arteries (n = 8,782). RESULTS: Clinically driven TLR was performed on 488 (5.6%) of the 8,782 patients during 5 years of follow-up. Male gender, older age, visible thrombus in the lesion, and larger stent diameter were associated with less TLR; multivessel disease and longer stents were associated with a higher risk of TLR. There was a substantial and highly significant reduction of the risk of any TLR after 5 years in the DES group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.36-0.52], p < 0.001). The effect of DES on TLR was limited in time to the first 2 years in the study with no evidence of a later rebound effect. The reduction in TLR after DES insertion was consistent across subgroups defined by gender, age, diabetes status, renal function, and lesion and stent characteristics. The number needed to treat with DES (vs. BMS) to prevent 1 TLR ranged from 4 to 110 across clinically relevant subgroups. CONCLUSION: DES have a time-limited effect on the rate of TLR, but with a substantial and highly significant reduction in the first 2 years after the procedure. This effect was found to be consistent across all important clinical subgroups.

Survival in Type 1 and Type 2 Diabetes in a Population Referred for Invasive Evaluation of Coronary Disease.

OBJECTIVES: To evaluate long-term and time trends of survival in patients with a clinical diagnosis of type 1 and type 2 diabetes compared to patients without diabetes in a population referred for invasive treatment of coronary disease. METHODS: Patients examined for heart disease at the Feiring LHL Clinics from March 1999 until December 2014 were followed for survival until 20 September, 2015. This yielded 43,872 patients with a known survival status including 1,326 (3.0%) patients with type 1 diabetes and 4,564 (10.9%) with type 2 diabetes. RESULTS: Cox regression revealed a hazard ratio (HR) in type 1 and type 2 diabetes, respectively, of 1.78 (95% confidence interval [CI] 1.60-1.99) and 1.29 (95% CI 1.21-1.37). Comparing survival in the treatment periods before and after 2007, patients without diabetes and with type 2 diabetes had a reduced HR of 0.78 (95% CI 0.72-0.84) and 0.76 (95% CI 0.63-0.91), respectively, but there was no reduction in type 1 diabetes (HR 1.03; 95% CI 0.74-1.42). CONCLUSIONS: Type 1 and type 2 diabetes have excess long-term mortality. In the nondiabetic and type 2 diabetic patients, a reduction in mortality has been noted in recent years, but has not been observed in type 1 diabetic patients.

Long-term survival after coronary bypass surgery and percutaneous coronary intervention.

OBJECTIVES: To assess whether there exists a long-term difference in survival after treatment with coronary bypass surgery or percutaneous coronary intervention in patients with coronary disease as judged by all-cause mortality. METHODS: Retrospective study from the Feiring Heart Clinic database of survival in 22 880 patients-15 078 treated with percutaneous coronary intervention and 7802 with bypass surgery followed up to 16 years. RESULTS: Cox regression and propensity score analysis showed no difference in survival for one-vessel and two-vessel disease during the whole study period. In three-vessel disease, however, the analysis revealed a consistent and highly significant survival benefit in the first 8 years with an HR of 0.76 (95% CI 0.69 to 0.84, p<0.001) in favour of bypass surgery with similar survival rates in the two treatment strategies after that time period. CONCLUSIONS: Treatment strategy did not affect survival in one-vessel and two-vessel disease, but bypass surgery offered an improved survival in the first 8 years in patients with three-vessel disease. These results are consistent with most previous reports and the survival benefit should be taken into account when selecting a strategy for this patient group.

Survival difference between coronary bypass surgery and percutaneous coronary intervention.

OBJECTIVES: To assess whether the previously observed lower death rate with coronary artery bypass surgery compared with percutaneous coronary intervention in subsets of patients with coronary artery disease persists in more recent years. DESIGN: Retrospective study from Feiring Heart Clinic database of survival in 17739 patients followed for 5 years after coronary revascularization. The cohorts treated in 1999-2005 and 2006-2011 were compared using Cox regression and propensity score analyses. RESULTS: Cox regression and propensity score analyses revealed no difference in survival in either time period in one- and two-vessel diseases. In three-vessel disease, the hazard ratios between bypass surgery and percutaneous intervention were 0.62 (95% confidence interval [CI]: 0.53-0.71, p < 0.001) and 0.59 (95% CI: 0.47-0.73, p < 0.001), respectively, in the two time periods, indicating persistent higher survival with bypass surgery. CONCLUSIONS: The previously observed lower death rate of coronary artery bypass surgery compared with percutaneous intervention in patients with three-vessel disease is persistent in more recent years and indicates that bypass surgery still should be the standard treatment for these patients.

Postoperatively increased serum alanine aminotransferase level is closely associated with mortality after cardiac surgery.

BACKGROUND: Hepatic biomarkers are often not assessed routinely after cardiac surgery. Alanine aminotransferase (ALT) has become the primary biomarker of any type of liver injury. Our purpose was to study the prognostic value of serum ALT in early and late mortality. METHODS: Patients subjected to any type of cardiac operation from January 1999 through December 2010 were studied. According to postoperative maximum ALT level, four groups were created: group 1 = ALT ≤ 50 U/L (n = 8,669), group 2 = ALT 50 to 150 U/L (n = 3,055), group 3 = ALT 151 to 500 U/L (n = 248), and group 4 = ALT > 500 U/L (n = 50). Cox multivariate modeling was used for survival analysis. RESULTS: Patients in groups 3 and 4 had increased 30-day mortality (hazard ratio [HR] = 8.07 [4.15-15.69], p < 0.001 and HR = 19.07 [9.88-36.80], p < 0.001, respectively). Late mortality was increased for group 4 after final adjustments (HR = 1.87 [1.18-2.95], p = 0.007). CONCLUSION: Elevated postoperative ALT level (above 150 U/L) is closely associated with early mortality after cardiac surgery. ALT level above 500 U/L implies a substantial liver dysfunction with a considerable negative association on both early and late survival.

Postcardioplegia ventricular fibrillation: no impact on subsequent survival.

OBJECTIVES: At aortic declamping after cardioplegic cardiac arrest, the initial rhythm can be broadly classified as ventricular fibrillation (VF) or non-VF. VF can be treated with potassium-induced conversion and direct-current countershock is only applied if potassium treatment fails. We aimed to investigate whether there are any differences between these groups of patients in regard to outcomes. DESIGN: From January 1999 through December 2010, 12,113 patients underwent various types of cardiac surgery. Data from every patient were consecutively registered. Survival was established through the Norwegian National Registry. Cox multivariable modeling with adjustment for clinical, biochemical, and medication baseline data was used for survival analysis. RESULTS: The mean follow-up time was 7.4 years and total patient-years were 89,268. The percentage of all-cause deaths was 24.9. Adjusted survival for patients with no postcardioplegia VF (n = 9723) and patients with successful potassium-induced conversion (n = 1877) was completely identical. Four hundred patients with electrical conversion after failed potassium treatment had a nonsignificant trend toward an increased mortality (hazard ratio, 95% confidence interval: 1.19 (0.99-1.4); p = 0.07). CONCLUSIONS: This is the first study reporting the association between postcardioplegia VF, its treatment with potassium and outcome. No impact was found on outcome as judged by all-cause mortality.

Potassium-induced conversion of ventricular fibrillation after aortic declamping.

OBJECTIVES: The anti-fibrillatory effect of potassium is well recognized from experimental models. There have, however, been very few clinical reports on the use of potassium to convert ventricular fibrillation (VF) after cardioplegic arrest. METHODS: In total, 8465 adult patients undergoing cardiac operations on cardiopulmonary bypass (CPB) and with cold antegrade crystalloid cardioplegic arrest were consecutively enrolled in a database. Patients with VF after removal of the aortic clamp were given 20 mmol potassium, and if needed an extra 10 mmol, in the perfusion line and the conversion rate was registered. Preoperative and intraoperative factors possibly related to the occurrence of post-ischaemic VF were assessed. RESULTS: Of these, 1721 (20%) patients had VF and 1366 of these (79%) were successfully treated with potassium infusion. Only 355 (21%) patients (4% of all operations) had direct-current countershock. The need for pacing was lower in the treatment group compared with the non-treatment group (P <0.001). Multivariate analysis revealed as the main findings that age, gender, amount of cardioplegia related to body mass index (BMI), and blood transfusion during the time of CPB had a highly significant (P <0.001) impact on reducing the rate of post-arrest VF. Somewhat contrary to expectation, left ventricular hypertrophy (LVH) was not a significant factor (P = 0.32) for post-arrest VF. No conversion by potassium was significant for age (P <0.001), gender (P <0.001) and LVH (P <0.001), but not for blood transfusion during CPB (P = 0.38) and for the ratio of cardioplegia-BMI (P = 0.26). CONCLUSIONS: The results from this register study demonstrate that potassium infusion is an effective and convenient first-hand measure to convert post declamping VF on CPB.

Cardiovascular risk of high- versus moderate-intensity aerobic exercise in coronary heart disease patients.

BACKGROUND: Exercise performed at higher relative intensities has been found to elicit a greater increase in aerobic capacity and greater cardioprotective effects than exercise at moderate intensities. An inverse association has also been detected between the relative intensity of physical activity and the risk of developing coronary heart disease, independent of the total volume of physical activity. Despite that higher levels of physical activity are effective in reducing cardiovascular events, it is also advocated that vigorous exercise could acutely and transiently increase the risk of sudden cardiac death and myocardial infarction in susceptible persons. This issue may affect cardiac rehabilitation. METHODS AND RESULTS: We examined the risk of cardiovascular events during organized high-intensity interval exercise training and moderate-intensity training among 4846 patients with coronary heart disease in 3 Norwegian cardiac rehabilitation centers. In a total of 175 820 exercise training hours during which all patients performed both types of training, we found 1 fatal cardiac arrest during moderate-intensity exercise (129 456 exercise hours) and 2 nonfatal cardiac arrests during high-intensity interval exercise (46 364 exercise hours). There were no myocardial infarctions in the data material. Because the number of high-intensity training hours was 36% of the number of moderate-intensity hours, the rates of complications to the number of patient-exercise hours were 1 per 129 456 hours of moderate-intensity exercise and 1 per 23 182 hours of high-intensity exercise. CONCLUSIONS: The results of the current study indicate that the risk of a cardiovascular event is low after both high-intensity exercise and moderate-intensity exercise in a cardiovascular rehabilitation setting. Considering the significant cardiovascular adaptations associated with high-intensity exercise, such exercise should be considered among patients with coronary heart disease.

Long-term survival after aortic valve replacement in octogenarians and high-risk subgroups.

OBJECTIVES: The increasing age in the population and improvements in the treatment options for aortic valvular disease have resulted in a considerable rise in the number of elderly patients being admitted for conventional aortic valve surgery. Recently, transcatheter aortic valve implantation (TAVI) has been developed as a less invasive treatment option. However, both open heart surgery and transcatheter treatment have serious complications. Thus, the knowledge of contemporary results of conventional surgery is important in guiding treatment allocation. METHODS: From the database at Feiring Heart Clinic, 1525 patients were identified who had undergone aortic valve replacement from 1999 to 2010; of these, 361 patients were more than 80 years of age. The population was followed for all-cause mortality until March 2011, with special reference to the age group older than 80 years and other high-risk subsets. RESULTS: The short-term mortality was 2.2% in the whole population and 3.9% in octogenarians. Five-year survival was 83.1 and 68.1%, respectively. In the high-risk subgroup of patients with a logistic EuroSCORE above 20%, the equivalent figures were 4.2 and 72.7%. CONCLUSIONS: Contemporary results after conventional aortic valve surgery are excellent in both short- and long-term survival and should not be withheld in the elderly or otherwise high-risk populations. The logistic EuroSCORE grossly overestimates the operative risk and should be used with caution in allocating patients to TAVI instead of conventional surgery.

Time dependent effect on mortality of drug-eluting stents versus bare metal stents.

OBJECTIVE: The comparison of all-cause long-term mortality between the use of drug-eluting stents versus bare metal stents in patients treated with percutaneous coronary interventions. DESIGN: Observational data from patients treated at Feiring Heart Clinic from 1999 until 2010 with a follow-up of survival at March 8, 2011. The survival was compared using Cox regression with ordinary covariates, propensity score used as covariate and 1:1 propensity score matching. RESULTS: The analyses included 5690 patients treated solely with bare metal stents and 2916 with drug-eluting stents. During the study period (October 2002 to March 2011), 996 deaths were observed. Due to nonproportional hazard effect on mortality of drug-eluting stents compared to bare metal stents, a landmark analysis splitting time at 9 months was employed. All analyses indicated a significantly reduced mortality by drug-eluting stents in the first 9 months with hazard ratios ranging from 0.42 to 0.51 with no difference in mortality from 9 months to 8 years of follow-up. CONCLUSIONS: Short-term mortality was significantly reduced in the drug-eluting stent group compared to the bare metal stent group. A selection bias could not be ruled out as an explanation for this effect. No difference was observed in mortality after 9 months.

Randomized prospective trial of saphenous vein harvest site infection after wound closure with and without topical application of autologous platelet-rich plasma.

OBJECTIVE: Wound infection is still a common problem after open long saphenous vein harvesting. Platelets are important for the healing process. The hypothesis was that spraying of the wounds with platelet-rich plasma might reduce the frequency of harvest site infections. METHODS: From January to October 2008, 140 patients undergoing first-time coronary artery bypass grafting were randomized into two groups of 70 patients. Both groups had standard surgical leg wound closure and care except topical application of platelet-rich plasma as adjunctive treatment in the active treatment group. End points were wound infection and cosmetic result at 6 weeks. RESULTS: The follow-up was 100% complete. Nine patients (13%) in the treatment group and eight (11%) in the control group experienced harvest site infection (p=0.80). The overall cosmetic result was also similar between the groups (p=0.34), but the top score was borderline and more frequent in the treatment group (p=0.050). CONCLUSION: Topical application of autologous platelet-rich plasma on vein harvest wounds did not reduce the rate of surgical site infection.

Coronary heart disease in women: less extensive disease and improved long-term survival compared to men.

OBJECTIVES: The aim of the study was to compare extent of coronary disease and subsequent long-term survival in women compared to men adjusted for baseline differences in demographics and morbidity. DESIGN: In the database at Feiring Heart Clinic 18 767 patients had a coronary angiographic examination in the period from March 1999 to December 31, 2006. Their survival status as of May 31, 2007 was ascertained through the Norwegian National Registry. Survival was compared using age stratified analyses and Cox regression adjusting for baseline differences. RESULTS: Significantly more women than men had no coronary disease (28.7 vs. 10.5%, p <0.001), while three vessel disease was more frequently present in men (38.7 vs. 21.8%, p <0.001), as judged by coronary angiography. Covariate adjusted survival was significantly better in women compared to men with an overall hazard ratio of 1.29 (p <0.001), but with no significant difference in the subgroup with high left ventricular end diastolic pressure. CONCLUSIONS: At the time of referral to invasive examination women had less extensive coronary artery disease than men as judged by coronary angiography and improved long-term survival when baseline differences were accounted for.

[Angiography with 64-channel CT upon suspicion of stable coronary disease]. / Angiografi med 64-kanalers CT ved mistenkt stabil koronarsykdom.

BACKGROUND: Invasive coronary angiography is the gold standard for diagnosing coronary artery disease. CT angiography (CTA) is a non-invasive alternative that is more available and less expensive. Previous Norwegian experience with 16-channel CT has been less successful than that reported from other countries. Improved image resolution has increased expectations of a better diagnostic accuracy, but a new local assessment of the method's usefulness is needed before routine usage is implemented. MATERIAL AND METHODS: Patients with suspected stabile coronary disease, referred to invasive coronary angiography, were first assessed with 64-channel CT angiography. Patients with atrial fibrillation or previous bypass operation were not included. All patients who fulfilled the eligibility criteria were included in the study (104), but 13 who had an Agatston calcium score > or = 800 and three for whom the examinations were technically unsuccessful were excluded; the study material therefore consisted of 88 patients. We assessed the method's ability (diagnostic accuracy) to detect diameter stenoses > or = 50% in coronary segments > or = 2 mm (without stent). RESULTS: When 4% non-interpretable segments were interpreted as positive (stenotic), the sensitivity was 97%, the specificity 78% and the positive and negative predictive values were 77 and 98% on a patient level. For 50 patients who did not have significant stenosis, CTA correctly identified 39, but overestimated the degree of stenosis in 11 patients. INTERPRETATION: 64-channel CTA is best at ruling out obstructive coronary artery disease in patients with intermediate risk of such disease. Few patients with significant lesions were missed due to false negative CTA evaluations, but false positive findings are a problem in low risk populations.

Coronary heart disease in diabetics: prognostic implications and results of interventions.

OBJECTIVES: The aim of the present study was to compare the extent of coronary disease and subsequent survival in diabetics and non-diabetics. DESIGN: From the database at Feiring Heart Clinic 13511 patients were identified with no previous revascularization and were examined with coronary angiography in the period from March 1999 to December 31, 2005. In the cohort 1,475 patients were diabetics. Their survival status of May 31, 2006 was ascertained through the Norwegian National Registry. RESULTS: Diabetics were more symptomatic and had a more severe coronary artery disease at the time of referral with more than 40% having three vessel disease. The unadjusted survival was lower in the diabetics. After adjustment through Cox regression, diabetes mellitus remained a risk factor for subsequent death (overall hazard ratio 1.33), with the excess mortality mainly residing in smoking diabetics. CONCLUSIONS: Diabetics were more severely diseased at the time of referral. In Cox regression diabetes mellitus remained a significant risk factor for death in smokers except in the cohort treated with CABG.

Survival after percutaneous coronary intervention and coronary artery bypass grafting in a single centre.

OBJECTIVES: Comparison of survival after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with coronary disease. DESIGN: Feiring Heart Clinic treated 10 815 patients with a coronary intervention (6366 PCI, 4449 CABG) from March 1999 to December 31, 2005. Their survival status as of May 31, 2006 was ascertained through the Norwegian National Registry. Survival in PCI and CABG cohorts was compared using Cox regression and propensity analysis. RESULTS: . Covariate adjusted survival was significantly improved by CABG compared to PCI in patients with three vessel disease with and without diabetes, with hazard ratios of 0.40 and 0.61, respectively. The difference was of borderline significance in patients with one/two vessel disease with diabetes, and no difference in survival between the strategies in patients with one/two vessel disease without diabetes. Propensity analysis supported these observations. Improved survival for the PCI cohort was observed in the last quintile of procedure times. CONCLUSIONS: Patients with three vessel disease with or without diabetes seem to have a survival benefit with CABG compared to PCI treatment.

Limited usefulness of non-invasive coronary angiography with 16-detector multislice computer tomography at a community hospital.

OBJECTIVES: To evaluate the usefulness of coronary angiography by 16-detector multislice spiral computed tomography (MSCT) in community hospital outpatients. DESIGN: MSCT was performed at the community hospital in 157 of 218 consecutive outpatients with suspected significant coronary disease, before referral for invasive coronary angiography. RESULTS: 101 patients had interpretable MSCT angiograms (64 men, age 62+/-10 years, calcium score 373+/-678, heart rate 56+/-7 beats/min, beta-blocker used by 91%). Coronary stenoses >50% were identified by invasive angiography in 49 patients. Only 79% of all segments could be assessed by MSCT due to heavy coronary calcification (12%) and blurred images (9%) in the remaining. By interpreting non-assessable segments as negative results 79 patients were correctly classified by MSCT. Sensitivity, specificity, positive and negative predictive values at patient level was 82%, 75%, 75% and 81%. By interpreting non-assessable segments as positive findings, the corresponding values were 100%, 29%, 57% and 100%, with correct diagnoses in 63% of patients. CONCLUSIONS: Limited diagnostic accuracy, non-interpretable scans and radiation exposure restrict the usefulness of coronary MSCT in a community hospital setting.