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Introduction: Coronary artery disease and malignancy occur more frequently in patients with type 2 diabetes. They may share inflammation as a possible common pathogenetic mechanism, but it is unclear whether a clinical correlation exists between them. Methods: This prospective cohort study followed 735 asymptomatic diabetics, aged 63.4 ± 5.3 years (mean ± standard deviation) for 12.2 ± 0.6 years after baseline coronary artery calcium scoring and cardiac computed tomography angiography. We examined extent and nature of coronary atherosclerosis and incidence of clinical cardiovascular (CV) events (death or myocardial infarction) and sought a relation to incidence of malignancy and malignancy mortality. Results: Total mortality was 16.5% (121/735 patients): malignancy was cause of death in 48/121 (39.7%) of these and CV events in 44/121 (36.3%). There was no relation between extent of coronary atherosclerosis and incident malignancy (plaque volume 127 [21, 427] mm3 (median [interquartile range]) for incident malignancy versus 153 [24, 427] mm3 no malignancy, p = 0.71) or death from malignancy (plaque volume 176 [26, 646] versus 144 [22, 411] mm3, p = 0.32). There was also no relation between presence of high-risk plaque and incident malignancy (high-risk plaque in 27.1% with malignancy vs. 21.6% without, p = 0.18) or fatal malignancy (p = 0.16). Incident and fatal malignancy were not related to clinical CV events. Independent predictors of incident and fatal malignancy were age, smoking at baseline, and elevated C-reactive protein. Conclusion: This study found no relation between extent of coronary atherosclerosis or incidence of CV events and malignancy. Malignancy surpassed CV disease as the commonest long-term cause of mortality in middle-aged and older diabetics.

Background The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD). Methods The study examined a population-based cohort of type 2 diabetics (n = 735) aged 55–74 years, recruited between 2006 and 2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of myocardial infarction (MI), stroke or cardiovascular death (MACE) was assessed over 10-years. Results Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06–7.86), 6.53 (2.47–17.29) and 8.3 (3.28–21) for CACS of 1–100, 101–300 and > 300 Agatston units respectively, compared to CACS = 0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555–0.676) versus PCE + CACS 0.696 (0.642–0.749); p = 0.0024]. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores. Conclusions CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories.

Aims The increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD). Methods and results The study examined a prospective population-based cohort of type 2 diabetics (n=735) aged 55–74 years, recruited between 2006–2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of MI, stroke or cardiovascular death (MACE) was assessed over 10-years. Risk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06–7.86), 6.53 (2.47–17.29) and 8.3 (3.28–21) for CACS of 1–100, 101–300 and >300 Agatston units respectively, compared to CACS=0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555–0.676) vs PCE + CACS 0.696 (0.642–0.749); p=0.0024[. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores. Conclusions CACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories. Funding Acknowledgement Type of funding sources: None.

Objectives The authors used coronary computed tomography angiography (CTA) to determine plaque characteristics predicting individual late plaque events precipitating acute coronary syndromes (ACS) in a cohort of asymptomatic type 2 diabetic patients. Background In patients with coronary artery disease, CTA plaque characteristics may predict mid-term patient events. Methods Asymptomatic patients with diabetes 55 to 74 years of age with no history of coronary artery disease (N = 630) underwent baseline 64-slice CTA and detailed plaque level analysis. All subsequent clinical events were recorded and adjudicated. In patients who developed ACS, culprit plaque was identified at invasive angiography and its precursor located on the baseline CTA. Plaque characteristics predicting an ACS-associated culprit plaque event were analyzed by time to event accounting for inpatient clustering of plaques and competing events. Results Among 2,242 plaques in 499 subjects, 24 ACS culprit plaques were identified in 24 subjects during median follow-up of 9.2 years (interquartile range: 8.4 to 9.8 years). Plaque volume (upper vs. lower quartile hazard ratio [HR]: 6.9; 95% confidence interval [CI]: 1.6 to 30.8; p = 0.011), percentage of low-density plaque content Conclusions In asymptomatic patients with type 2 diabetes, CTA plaque volume, percent low-density plaque content, and mild calcification predicted late plaque events. The additional presence of luminal stenosis increased the probability of an acute event.

Objectives: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. Methods: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). Results: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. Conclusions: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. Key Points: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

We examined 18,654 patients who underwent cardiac catheterization in a single center to clarify the association between catheterization indication, body mass index (BMI), and long-term survival over a mean follow-up of 81 months. Patients were grouped by indication for catheterization: (a) acute coronary syndromes (ACS), 7,426 patients; (b) coronary artery disease (CAD) evaluation in stable clinical presentation, 6,911 patients; and (c) primarily non-CAD cardiac evaluations, 4,317 patients. Compared with normal weight, overweight and obesity (but not morbid obesity) was associated with lower risk of long-term mortality. Underweight patients had the greatest risk of mortality. After multivariate adjustment, survival benefit of the overweight and obese was retained in the ACS group [hazard ratio 0.86, 95% confidence interval (0.77-0.96), p = 0.006 and 0.79, (0.68-0.91), p = 0.001, respectively] and in overweight patients in the stable presentation CAD group [0.83, (0.72-0.94), p = 0.005], whereas there was no survival benefit in any of the BMI categories in those catheterized primarily for non-CAD indications. Further analysis of matched cohorts showed similar patterns of survival benefit of the overweight/obese. In conclusion, among patients who underwent cardiac catheterization, an inverse association between BMI and long-term mortality was observed, with the lowest risk noted in the overweight and obese population; the obesity paradox was principally demonstrated in patients with ACS, and was eliminated after covariate adjustment in those catheterized primarily for non-CAD indications.

Background Familial hypercholesterolemia is characterized by markedly increased low-density lipoprotein cholesterol and risk for premature atherosclerotic cardiovascular disease. Models of care vary and reflect differing health policies and resources. The availability of electronic databases may enable better identification and assessment of familial hypercholesterolemia in the community. Methods A regional healthcare database was utilized to identify patients with a high probability of familial hypercholesterolemia, clinically defined by age-dependent-peak low-density lipoprotein cholesterol cutoffs and exclusion of secondary causes of severe hypercholesterolemia. Clinical characteristics, low-density lipoprotein cholesterol goal attainment, and treatment gaps were investigated. Results Probable familial hypercholesterolemia was diagnosed in 1932 of 685,314 individuals (1:355; median age 47 years). Atherosclerotic cardiovascular disease was present in 16.3% of adults (38% in males aged 50-74 years). Median peak low-density lipoprotein cholesterol was 264 mg/dl (interquartile range 252-288). Statins and/or ezetimibe were prescribed to 83% of patients and high-intensity statins to 53%, whereas prescriptions were filled in 57% and 40% cases respectively over the last six months, p 0.001. Treatment gaps were wider among ethnic minorities, younger individuals, and those without atherosclerotic cardiovascular disease. Low-density lipoprotein cholesterol 100 mg/dl was attained in 10.1% overall and 28.7% of those with atherosclerotic cardiovascular disease. Predictors of low-density lipoprotein cholesterol goal attainment included recent issue of high-intensity statins, presence of atherosclerotic cardiovascular disease, diabetes, older age and lack of smoking. Conclusions The population with high probability for familial hypercholesterolemia was characterized by low attainment of low-density lipoprotein cholesterol treatment goals despite high prescription rates of lipid-lowering medications. Low utilization of intensified therapies, non-adherence, and ethnic disparities were contributing factors. These findings emphasize the need to improve awareness and quality of care of familial hypercholesterolemia in the community.

Contemporary data on clinical profiles and long-term outcomes of young adults with coronary artery disease (CAD) are limited.To determine the risk profile, presentation, and outcomes of young adults undergoing coronary angiography.A retrospective analysis (2000-2017) of patients aged ≤ 35 years undergoing angiography for evaluation and/or treatment of CAD was conducted.Coronary angiography was performed in 108 patients (88% males): 67 acute coronary syndrome (ACS) and 41 non-ACS chest pain syndromes. Risk factors were similar: dyslipidemia (69%), positive family history (64%), smoking (61%), obesity (39%), hypertension (32%), and diabetes (22%). Eight of the ACS patients (12%) and 29 of the non-ACS (71%) had normal coronary arteries without subsequent cardiac events. Of the 71 with angiographic evidence of CAD, long-term outcomes (114 ± 60 months) were similar in ACS compared to non-ACS presentations: revascularization 41% vs. 58%, myocardial infarction 32% vs. 33%, and all-cause death 8.5% vs. 8.3%. Familial hypercholesterolemia (FH) was diagnosed in 25% of those with CAD, with higher rates of myocardial infarction (adjusted hazard ratio [HR] 2.62, 95% confidence interval [95%CI] 1.15-5.99) and revascularization (HR 4.30, 95%CI 2.01-9.18) during follow-up. Only 17% of patients with CAD attained a low-density lipoprotein cholesterol treatment goal70 mg/dl.CAD in young adults is associated with marked burden of traditional risk factors and high rates of future adverse cardiac events, regardless of acuity of presentation, especially in patients with FH, emphasizing the importance of detecting cardiovascular risk factors and addressing atherosclerosis at young age.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Background Coronary artery disease often progresses more rapidly in diabetics, but the integrated impact of diabetes and early revascularization status on late or repeat revascularization in the contemporary era is less clear. Methods Coronary angiography was performed in 12,420 patients between the years 2000–2015 and early revascularization status [none, percutaneous coronary intervention (PCI) or bypass surgery (CABG)] was determined. Subsequent revascularization procedures were recorded over a median follow-up of 67 months and its relation to diabetic and baseline revascularization status was studied. Results Early revascularization status was none in 5391, PCI in 5682 and CABG in 1347 patients. Late revascularization rates were 10, 26 and 11.1% respectively. Diabetes was present in 37%; a stepwise relationship of diabetic status with late revascularization was observed: no diabetes (reference) 14.4%, non-insulin treated diabetes 21% (adjusted HR 1.35, 95% CI 1.23–1.49, p

The authors used coronary computed tomography angiography (CTA) to determine plaque characteristics predicting individual late plaque events precipitating acute coronary syndromes (ACS) in a cohort of asymptomatic type 2 diabetic patients.In patients with coronary artery disease, CTA plaque characteristics may predict mid-term patient events.Asymptomatic patients with diabetes 55 to 74 years of age with no history of coronary artery disease (N = 630) underwent baseline 64-slice CTA and detailed plaque level analysis. All subsequent clinical events were recorded and adjudicated. In patients who developed ACS, culprit plaque was identified at invasive angiography and its precursor located on the baseline CTA. Plaque characteristics predicting an ACS-associated culprit plaque event were analyzed by time to event accounting for inpatient clustering of plaques and competing events.Among 2,242 plaques in 499 subjects, 24 ACS culprit plaques were identified in 24 subjects during median follow-up of 9.2 years (interquartile range: 8.4 to 9.8 years). Plaque volume (upper vs. lower quartile hazard ratio [HR]: 6.9; 95% confidence interval [CI]: 1.6 to 30.8; p = 0.011), percentage of low-density plaque content 50 Hounsfield units (HR: 14.2; 95% CI: 1.9 to 108; p = 0.010), and mild plaque calcification (HR vs. all other plaques 3.3 [95% CI: 1.5 to 7.3]; p = 0.004) predicted plaque events univariately and after adjustment by clinical risk score. A culprit plaque event occurred in 13 of 376 (3.5%) high-risk plaques (HRP) (plaques with ≥2 risk predictors) versus 11 of 1,866 (0.6%) in non-HRPs (p 0.0001), at 12 of 343 (3.5%) stenotic sites (≥50%) versus 12 of 1,899 (0.6%) nonstenotic sites (p 0.0001) and in 7 of 131 (5.3%) HRP with stenosis (p 0.0001 vs. all others). In 130 (20.6%) subjects, no coronary plaque was present on baseline CTA.In asymptomatic patients with type 2 diabetes, CTA plaque volume, percent low-density plaque content, and mild calcification predicted late plaque events. The additional presence of luminal stenosis increased the probability of an acute event.

Autonomic control of the cardiovascular system may be impaired in type 2 diabetes and is associated with increased morbidity and mortality. Parameters obtained during stress testing may reflect early stages of cardiac autonomic dysfunction and provide prognostic information in asymptomatic type 2 diabetes.We performed maximal exercise treadmill testing in 594 patients with type 2 diabetes without known coronary heart disease. The prognostic significance of physiological parameters associated with autonomic dysfunction was assessed, including chronotropic incompetence (80% heart rate reserve), abnormal heart rate recovery at 1 minute18 beats/minute, and resting tachycardia100 beats/minute. Cox proportional hazards analysis was used to determine the association of exercise parameters with a composite outcome of all-cause mortality, myocardial infarction or stroke.Resting heart rate100 beats/minute was observed in 18% of patients, chronotropic incompetence in 30% and heart rate recovery at 1 minute18 beats/minute in 35%. Over 79 ± 16 months, there were 72 (12%) events. Each parameter was significantly associated with event risk in an adjusted multivariate analysis: chronotropic incompetence (hazard ratio 1.89, 95% confidence interval 1.18-3.01; P = 0.008), resting heart rate ≥100 beats/minute (hazard ratio 1.97, 95% confidence interval 1.19-3.26; P = 0.008) and heart rate recovery at 1 minute18 beats (hazard ratio 1.77, 95% confidence interval 1.12-2.81; P = 0.015). A progressive relationship between the number of abnormal parameters and event risk was observed (log rank P 0.001).Chronotropic incompetence, resting tachycardia and reduced heart rate recovery are independently and additively associated with long-term mortality, myocardial infarction or stroke in type 2 diabetes without known coronary heart disease.

A 256-slice coronary computed tomography angiography (CCTA) is an accurate method for detection and exclusion of obstructive coronary artery disease (OBS-CAD). However, accurate image interpretation requires expertise and may not be available at all hours. The purpose of this study was to evaluate the usefulness of a fully automated computer-assisted diagnosis (COMP-DIAG) tool for exclusion of OBS-CAD in patients in the emergency department (ED) presenting with chest pain. Three hundred sixty-nine patients in ED without known coronary disease underwent 256-slice CCTA as part of the assessment of chest pain of uncertain origin. COMP-DIAG (CorAnalyzer II) automatically reported presence or exclusion of OBS-CAD (>50% stenosis, ≥1 vessel). Performance characteristics of COMP-DIAG for exclusion and detection of OBS-CAD were determined using expert reading as the reference standard. Seventeen (5%) studies were unassessable by COMP-DIAG software, and 352 patients (1,056 vessels) were therefore available for analysis. COMP-DIAG identified 33% of assessable studies as having OBS-CAD, but the prevalence of OBS-CAD on CCTA was only 18% (66 of 352 patients) by standard expert reading. However, COMP-DIAG correctly identified 61 of the 66 patients (93%) with OBS-CAD with 21 vessels (2%) with OBS-CAD misclassified as negative. In conclusion, compared to expert reading, automated computer-assisted diagnosis using the CorAnalyzer showed high sensitivity but only moderate specificity for detection of obstructive coronary disease in patients in ED who underwent 256-slice CCTA. The high negative predictive value of this computer-assisted algorithm may be useful in the ED setting.

Despite its well-established prognostic value, cardiorespiratory fitness (CRF) is not incorporated routinely in risk assessment tools. Whether low CRF provides additional predictive information in asymptomatic type 2 diabetics beyond conventional risk scores and coronary artery calcification (CAC) is unclear.We studied 600 type 2 diabetics aged 55-74 years without known coronary heart disease. CRF was quantified in metabolic equivalents (METs) by maximal treadmill testing and categorized as tertiles of percent predicted METs (ppMETs) achieved. CAC was calculated by non-enhanced computed tomography scans. The individual and joint association of both measures with an outcome event of all-cause mortality, myocardial infarction or stroke, was determined over a mean follow-up period of 80 ± 16 months.There were 72 (12%) events during follow-up. Low CRF was independently associated with event risk after adjustment for traditional risk factors and CAC (HR 2.25, 95% CI 1.41-3.57, p = 0.001). CRF (unfit/fit) allowed further outcome discrimination both amongst diabetics with low CAC scores (9.5% versus 2.0% event rate), and amongst diabetics with high CAC scores (23.5% versus 12.4% event rate), p 0.001. The addition of CRF to a model comprising UKPDS and CAC scores improved the area under the curve for event prediction from 0.66 to 0.71, p = 0.03, with a positive continuous net reclassification improvement (NRI) of 0.451, p = 0.002.CRF, quantified by ppMETs, provided independent prognostic information which was additive to CAC. Low CRF may identify asymptomatic diabetic subjects at higher risk for all-cause mortality, myocardial infarction or stroke, despite low CAC.

Flow-limiting aorto-ostial coronary lesions are clinically important because they subtend a large myocardial territory and may induce extensive myocardial ischemia. Diagnosis and treatment of these lesions is challenging and procedural success and clinical outcomes are inferior to non-ostial lesions. The purpose of this review is to summarize current knowledge regarding aorto-ostial percutaneous coronary intervention and to suggest novel approaches for optimizing these procedures.

Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of90 minutes.To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes.In March 2013 the authors launched a seven-component intervention program: Direct patient evacuation by out-of-hospital emergency medical services to the coronary intensive care unit or catheterization laboratory Education program for the emergency department staff Dissemination of information regarding the urgency of the PPCI decision Activation of the catheterization team by a single phone call Reimbursement for transportation costs to on-call staff who use their own cars Improvement in the quality of medical records Investigation of failed cases and feedback.During the 14 months prior to the intervention, initiation of catheterization occurred within 90 minutes of hospital arrival in 88/133 patients(65%); during the 18 months following the start of the intervention, the rate was 181/200 (90%) (P0.01). The respective mean/median times to treatment were 126/67 minutes and 52/47 minutes (P0.01). Intervention also resulted in shortening of the time interval from hospital entry to PPCI on nights and weekends.Following implementation of a comprehensive intervention, the time from hospital admission to PPCI of STEMI patients shortened significantly, as did the proportion of patients treated within 90 minutes of hospital arrival.

Background Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular disease (ASCVD). The introduction of potent therapeutic agents underlies the importance of improving clinical diagnosis and treatment gaps in FH.Methods and Results:A regional database of 1,690 adult patients with high-probability FH based on age-dependent peak-low-density lipoprotein cholesterol (LDL-C) cut-offs and exclusion of secondary causes of severe hypercholesterolemia, was examined to explore the clinical manifestations and current needs in the management of ASCVD, which was present in 248 patients (15%), of whom 83% had coronary artery disease (CAD); 19%, stroke; and 13%, peripheral artery disease. ASCVD was associated with male gender, higher peak LDL-C, lower high-density lipoprotein cholesterol (HDL-C), and traditional risk factor burden. Despite high-intensity statin (prescribed in 83% and combined with ezetimibe in 42%), attainment of LDL-C treatment goals was low, and associated with treatment intensity and drug adherence. Multivessel CAD (adjusted hazard ratios (HR), 3.05; 95% CI: 1.65-5.64), myocardial infarction, and the presence of ≥1 traditional risk factor (HR, 2.59; 95% CI: 1.42-4.71), were associated with repeat coronary revascularizations, in contrast with peak LDL-C >300 mg/dL (HR, 1.13; 95% CI: 0.66-1.91). Conclusions Main manifestations of ASCVD in FH patients were premature, multivessel CAD with need for recurrent revascularization, associated with classical cardiovascular risk factors but not with peak LDL-C. In spite of intensive therapy with lipid-lowering agents, treatment gaps were significant, with low attainment of LDL-C treatment goals.

Objectives: Predictive models for heart failure (HF) in heterogeneous populations have had limited success. We examined cardiac computed tomography angiography (CTA) predictors of HF or cardiovascular death (HF-CVD) in a prospective study of asymptomatic diabetics undergoing baseline assessment by CTA. Methods: The subjects (n = 735, aged 55-74 years, 51.2% women) had no clinical history of cardiovascular disease at study entry. Coronary artery calcium (CAC) score, CTA-defined coronary atherosclerosis, cardiac chamber volumes, and clinical data were collected and late outcome events recorded over 8.4 ± 0.6 years (range 7.3-9.3). Results: HF-CVD occurred in 41 (5.6%) subjects, with HF occurring mostly (19/23, 82.6%) in subjects without preceding myocardial infarction. Baseline univariate clinical outcome predictors of HF-CVD included older age (p = 0.027), the duration of diabetes (p = 0.004), HbA1c (p < 0.0001), microvascular disease (retinopathy, microalbuminuria) (p < 0.0001), and systolic blood pressure (p = 0.035). Baseline univariate CTA predictors included CAC score (p = 0.004), coronary stenosis (p = 0.047), and a CTA-defined left/right atrial (LA/RA) volume ratio >1 (p < 0.0001). Independent predictors were an LA/RA volume ratio >1, microvascular disease, and systolic blood pressure (model C-statistic 0.792, 95% CI 0.758-0.824). Measures of the extent of coronary artery disease (CAD) were not independent predictors of HF-CVD. Conclusions: In a low- to moderate-risk asymptomatic diabetic population, CTA LA enlargement (LA/RA volume ratio) but not the extent of CAD had independent prognostic value for HF-CVD in addition to the clinical variables.

Impaired cardiorespiratory fitness (CRF) is a potent risk factor for mortality in diabetes, and may modify the relation between adiposity and mortality. We evaluated the interaction between CRF and abdominal adiposity distribution with all-cause mortality, myocardial infarction or stroke in patients with diabetes.We studied 294 type 2 diabetics without known coronary artery disease. CRF was quantified in metabolic equivalents by maximal treadmill testing, and categorized as low CRF (first tertile) or high CRF (second and third tertiles). Abdominal fat was quantified as subcutaneous or visceral adipose tissue from non-enhanced computed tomography scans. Association of CRF, adiposity distribution and their interaction with all-cause mortality, myocardial infarction or stroke was assessed by Cox proportional-hazard models.There were 31 (11%) events during 62 ± 12 months. Low CRF was significantly associated with event risk before and after adjustment for each measure of adiposity (hazard ratio 3.79, 95% confidence interval 1.79-8.01, p 0.001). CRF level was inversely correlated with subcutaneous (r = -0.44, p 0.001) but not visceral adipose tissue (r = -0.06, p = 0.31). Absolute event rates increased progressively across visceral adipose tissue tertiles, but decreased across subcutaneous tertiles. However, within each tertile of both adiposity measures, increased events were observed in the low compared with the high CRF group; this trend was also observed in an adjusted multivariate proportional hazards model.Although subcutaneous and visceral adipose tissues differed in their association with CRF levels and absolute event rates, lower baseline CRF in type 2 diabetics was significantly associated with higher risk of all-cause mortality, myocardial infarction or stroke, regardless of abdominal adiposity pattern.

Background— During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results— Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE–eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69–1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04–1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80–1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions— During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00808067.

We assessed the performance of a new-generation, 256-row computed tomography (CT) scanner for detection of obstructive coronary artery disease (CAD) compared to invasive quantitative coronary angiography. A total 121 consecutive symptomatic patients without known CAD referred for invasive coronary angiography (age 59 ± 12 years, 37% women) underwent clinically driven 256-row coronary computed tomographic angiography (CCTA) before the invasive procedure. Obstructive CAD (>50% diameter stenosis) was assessed visually on CCTA by 2 independent observers using the 18-segment society of cardiovascular CT model and on invasive angiograms using quantitative coronary angiography (the reference standard). Observers were unaware of the findings from the alternate modality. Nonassessable coronary computed tomographic angiographic segments were considered obstructive for the purpose of analysis. Quantitative coronary angiography demonstrated obstructive CAD in 145 segments in 82 of 121 patients (68%). Overall, 1,677 coronary segments were available for comparative analysis, of which 39 (2.3%) were nonassessable by CCTA, mostly because of heavy calcification. Patient-based and segment-based analysis showed a sensitivity of 100% and 97% (95% confidence interval 95% to 100%) and specificity of 69% (95% confidence interval 55% to 84%) and 97% (confidence interval 96% to 98%), respectively. Four segments with obstructive CAD in 4 patients were not detected by CCTA. All 4 patients had additional coronary obstructions identified by CCTA. The predictive accuracy was 90% (range 85% to 95%) for patient based and 97% (96% to 98%) for segment based analysis. In conclusion, 256-row CCTA showed high sensitivity and high predictive accuracy for detection of obstructive CAD in patients without previously known disease. Although coronary calcification might still interfere with analysis, the rate of nonassessable segments was low.

Visceral abdominal adipose tissue (VAT) may play an active role in the progression of coronary atherosclerosis. We examined the relation between VAT, non-alcoholic fatty liver disease and extent of coronary atheroma in patients with type 2 diabetes mellitus but no known coronary artery disease.Coronary artery calcium and area, distribution and thickness of upper abdominal fat were measured in selected axial cross-sections from non-enhanced computed tomography (CT) scans of the chest. Coronary atheroma was assessed visually on a per vessel basis from 64 slice CT angiography using axial views and multi-format reconstructions. Fatty liver was diagnosed when liver density was40 Hounsfield units (HU) or ≥10 HU below spleen density.The area of VAT was increased in patients with versus without multi-vessel coronary artery plaque (237.0 ± 101.4 vs 179.2 ± 79.4 mm(2), p0.001). Waist circumference (101.6 ± 12.3 versus 95.3 ± 13.8 cm) and internal abdominal diameter (218.7 ± 33.0 vs 194.6 ± 25.7 mm) (both p0.001) were increased in patients with multi-vessel plaque whereas subcutaneous fat was unrelated to coronary plaque. Presence of fatty liver (93/318 patients, 29.2%) did not correlate with presence or extent of coronary plaque. The correlation of VAT with multi-vessel plaque although nominally independent of the metabolic syndrome (p=0.04) was not independent of waist circumference.In asymptomatic subjects with DM and no history of CAD area of VAT correlated with the presence and extent of coronary atheroma but as a risk predictor added little independent information to that obtained by more readily obtainable measures of adiposity-waist circumference and internal abdominal diameter.

To understand the current impact of diabetes mellitus (DM) on long-term outcomes among patients referred for coronary angiography, we studied 14,337 consecutive patients (5,279 diabetic patients [37%]) referred to coronary angiography for assessment or treatment of coronary artery disease. We investigated long-term all-cause mortality and its interaction with hypoglycemic therapy and presenting coronary status. At baseline, patients with DM had more hypertension, hyperlipidemia, and renal failure; more were women, overweight, and more had previous coronary interventions. Mortality was higher in those with DM and was related to treatment status: multivariate adjusted hazard ratio during a median follow-up period of 78 months was 1.41 (95% CI 1.11 to 1.80, p = 0.006) for diet only-treated DM, 1.63 (95% CI 1.51 to 1.77, p0.001) for DM treated with oral hypoglycemics, and 2.50 (95% CI 2.20 to 2.85, p0.001) for DM requiring insulin therapy. The earlier findings were similar in magnitude in patients presenting with acute or stable coronary syndromes. In addition, long-term mortality of medically treated DM presenting with a stable coronary syndrome was even higher than that of nondiabetic patients presenting with an acute coronary syndrome (hazard ratio 1.21, 95% CI 1.08 to 1.35, p = 0.001). In conclusion, in patients referred for coronary angiography in the current era, DM remained an independent predictor of long-term mortality regardless of the coronary presentation and mortality increased in direct relation to intensity of hypoglycemic therapy at presentation.

Radial artery occlusion (RAO) may occur following transradial catheterization, precluding future use of the vessel for vascular access or as a coronary bypass graft. Recanalization of RAO may occur; however, long-term radial artery patency when revascularization is more likely to be required has not been investigated. Transradial catheterization is usually performed via 5-Fr or 6-Fr catheters. Insertion of 7-Fr sheaths into the radial artery enables complex coronary interventions but may increase the risk of RAO.To assess the long-term radial artery patency following transradial catheterization via 7-Fr sheaths.Antegrade radial artery blood flow was assessed by duplex ultrasound in 43 patients who had undergone transradial catheterization via a 7-Fr sheath.All patients had received intravenous unfractionated heparin with a mean activated clotting time (ACT) of 247 ± 56 seconds. Twenty-four patients (56%) had received a glycoprotein IIbIIIa inhibitor and no vascular site complications had occurred. Mean time interval from catheterization to duplex ultrasound was 507 ± 317 days. Asymptomatic RAO was documented in 8 subjects (19%). Reduced body weight was the only significant univariate predictor of RAO (78 ± 11 vs. 89 ± 13 kg, P = 0.031). In a bivariate model using receiver operator characteristic (ROC) curves, the combination of lower weight and shorter ACT offered best prediction of RAO (area under the ROC curve 0.813).Asymptomatic RAO was found at late follow-up in approximately 1 of 5 patients undergoing transradial catheterization via a 7-Fr sheath and was associated with lower body weight and shorter ACT.

Background Type 2 diabetics are at increased risk for vascular events, but the value of further risk stratification for coronary heart disease ( CHD ) in asymptomatic subjects is unclear. We examined the added value of coronary computed tomography angiography over clinical risk scores (United Kingdom Prospective Diabetes Study), and coronary artery calcium in a population‐based cohort of asymptomatic type 2 diabetics. Methods and Results Subjects (n=630) underwent baseline clinical assessment and computed tomography angiography (64‐slice scanner). Plaque site, volume, calcific content, and arterial remodeling were recorded using dedicated software. Coronary, macrovascular, and microvascular‐related events were assessed over 6.6±0.6 (mean± SD ) (range 5.4–7.5) years and all CHD events were adjudicated. Discrimination of CHD events (cardiovascular death, myocardial infarction, unstable angina, or new‐onset angina requiring intervention) (n=41) was improved by addition of total plaque burden to the clinical risk and coronary artery calcium scores combined (C=0.789 versus 0.763, P =0.034) and further improved by addition of an angiographic score (C=0.824, P =0.021). Independent predictors of a CHD event were United Kingdom Prospective Diabetes Study risk score (hazard ratio 1.3 per 10% 10‐year risk, P =0.003) and the angiographic score (hazard ratio 3.2 per quartile, P CHD event (hazard ratio 3.0, P =0.02). Computed tomography angiography predicted combined macrovascular but not microvascular‐related events. Conclusions Computed tomography angiography provides additional prognostic information in asymptomatic type 2 diabetics not obtainable from clinical risk assessment and coronary artery calcium alone.

Patients with severe familial hypercholesterolemia (FH) are often unrecognized despite typical presentation. The introduction of PCSK9 inhibitors opens new therapeutic options and emphasizes the need for identification of severe FH patients.The objective was identification, characterization, and management of severe FH patients by screening of cardiac catheterization (CC) database.Retrospective analysis of CC database from 2002 to mid-2015 was performed for low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL (n = 2383). Severe FH was diagnosed if any prior LDL-C was ≥280 mg/dL, excluding secondary causes. Peak/current LDL-C levels and lipid-lowering therapies were evaluated. Initial attempt was made to detect relatives with FH according to identifying data and age-dependent LDL-C cutoffs.Severe FH was identified in 54 of initial 2382 patients with CC LDL-C ≥130 mg/dL. Mean age at cardiovascular disease diagnosis was 45 years. Peak LDL-C was 280 to 464 mg/dL (median, 322). Coronary artery bypass graft surgery was performed in 26 patients (48%) and redo coronary artery bypass graft surgery in 5 patients (9%). Risk factors included obesity (33%), hypertension (59%), smoking (33%), and diabetes (24%). LDL-C reduction ≥50% of peak value was achieved in 56%, LDL-C130 mg/dL in 32%, and LDL-C100 mg/dL in 17% of patients. High-intensity statin plus ezetimibe was prescribed for 67%, high-intensity statin alone for 24%, and other lipid-lowering therapies for 9% of patients. Treatment intensity was directly associated with attainment of LDL-C goals. Matching probands' surnames and place of residency with district health maintenance organization database has identified 161 additional individuals with possible FH; 58% were not treated with lipid-lowering drugs.A simple algorithm for identification of patients with severe FH was implemented based on large catheterization and health maintenance organization databases and revealed patients with severe FH and coronary disease at a young age, with low attainment of cholesterol treatment goals. Screening existing cardiovascular databases of populations at risk will promote identification and management of severe FH patients and their affected family members.

To evaluate, objectively and subjectively, the feasibility of 256-row computed tomography coronary angiography (CTCA) in obese patients. 256-row CTCA was performed in 68 symptomatic patients (age 61 ± 10 years, 37 females), 39 obese (body mass index-BMI30 kg/m(2)) and 29 non-obese. Retrospective analysis was performed by two observers who assessed the image quality of each coronary segment using a 4-point subjective scale (1 excellent to 4 non-diagnostic), and another blinded observer measured objective image parameters. BMI in the obese group was 35 ± 5 (32-65) Kg/m(2), and 24 ± 3 (16-29) Kg/m(2) in the non-obese (P = 0.004). Average subjective image quality was similar in obese (1.41 ± 0.40) and non-obese (1.34 ± 0.40) patients, P = 0.17. Proportion of coronary artery segments with non-diagnostic image quality was low in both groups (0.7% in obese and 0.2% in non-obese, P = 0.31). Signal to noise and contrast to noise ratios were not significantly lower in obese than in non-obese patients (9.4 ± 3 vs. 12 ± 2.5, P = 0.16 and 11.1 ± 3.8 vs. 13.7 ± 2.9, P = 0.07 respectively). However, dose length product (1167 ± 567 vs. 827 ± 375 mGy × cm, P = 0.014) and image noise (44 ± 13 vs. 35 ± 5 HU, P0.001) were higher in the obese patient group. Image quality was preserved in obese patients undergoing 256-row CTCA at the cost of increased radiation exposure and image noise.

Metallic stent struts cause imaging artifacts on multidetector computed tomography (MDCT) which interfere with the assessment of in-stent coronary restenosis. We examined the degree of image distortion of implanted coronary stents on MDCT, comparing different stent types, sizes and orientation.We quantified stent dimensions and image distortion of 151 non-opacified coronary stents in 89 patients (81% men, age 65+/-10 years) who underwent MDCT with a 40 slice MDCT scanner. Stent dimension by MDCT was compared with measurements obtained from quantitative coronary angiographic (QCA) in the immediate post-implantation angiogram and with manufacturers' data.Stent image quality was good for 107 stents (71%), moderate for 38 (25%) and poor in 6 (4%), 2 (1%) of which were not assessable. Blooming artifact resulted in a mean MDCT luminal (inner) diameter 30+/-14% smaller than QCA diameter (2.0+/-0.5 vs 2.9+/-0.3 mm, p0.001) and a mean outer diameter exceeding QCA by 31+/-14% (3.8+/-0.5 vs 2.9+/-0.3 mm, p0.001). MDCT luminal stent diameter was unrelated to strut thickness or the vessel stented but appeared to be smaller for vertically orientated stents (p=0.017), cobalt alloy (vs stainless steel) (p=0.011) and also for different stent types (p=0.006).The luminal dimension of implanted coronary stents, as visualized with 40 slice MDCT, was one third smaller than on invasive angiography. This decrease in visualized stent luminal diameter forms the basis for the difficulty in accurate assessment of in-stent restenosis by MDCT.

Contrast-enhanced multidetector-row computed tomography (MDCT) is now capable of providing high-quality noninvasive views of cardiac anatomy and ‘instant’ noninvasive coronary angiography. With current generation 64-slice scanners, MDCT can be performed in most patients with minimal patient discomfort and high diagnostic accuracy. MDCT may obviate the need for invasive diagnostic angiography in patients with borderline symptoms or equivocal noninvasive testing. It is useful in assessing the symptomatic patient postrevascularization and in emergency room triage in selected patients with chest pain. Calcified vessels are still difficult to assess, as is the accurate evaluation of implanted coronary stents. The volume of contrast material required for proper opacification limits the use of MDCT in patients with renal dysfunction, but newer emerging technologies will greatly improve these disadvantages in the near future. MDCT is expected to become an integral part of our diagnostic armamentarium in the cardiac patient.

The usefulness of 64-slice multidetector coronary computed tomography (MDCT) in a diagnostic triage of 100 consecutive patients (age 55.8+/-11.6 years; 57% men) with chest pain suspected to be ischemic in origin and a negative or nondiagnostic exercise treadmill test (ETT) result was examined. None of the patients had previously known coronary artery disease (CAD). MDCT showed obstructive (>or=50%) CAD in 29 patients; 13 of 59 patients (22%) with a negative and 16 of 41 patients (39%) with a nondiagnostic ETT result. High-risk (left main and/or 3-vessel) CAD was present in 3.3% of patients with a negative and 4.9% with a nondiagnostic ETT result. The 29 patients with obstructive CAD on MDCT had a higher mean Agatston calcium score (221+/-402 vs 40+/-77 U, p

Background: Several trials suggested superiority of primary percutaneous coronary intervention (PPCI) angioplasty over thrombolysis in patients with ST-elevation myocardial infarction (STEMI), but many trials were characterized by low rates of early revascularization in patients treated with initial thrombolysis. We tested the hypothesis that in patients with hemodynamically stable STEMI, initial thrombolysis followed by an active early rescue/definitive revascularization strategy could achieve salutary short- and long-term outcomes. Methods: A prospective registry documented all 212 STEMI patients who received initial thrombolytic therapy over a 2-year period in a single medical center. Median patient age was 58 (range: 29–92) years, 47 (22%) patients were aged >70 years and 18 (8%) >80 years. Fifty-two (25%) patients underwent rescue angioplasty Results: Thirty-day mortality was 4.7% and 1-year mortality 6.7%. Mortality was not related to diabetes mellitus, hypertension, anterior infarction location, fibrin-specific thrombolytic drug or rescue PCI. By multivariate analysis, in-hospital definitive angiography/revascularization (p < 0.0001) and TIMI risk score >3 on admission (p < 0.01) were significant independent predictors of both 30 day and 12 month outcome. Conclusions: Initial thrombolysis was useful and effective in real-world STEMI patients when coupled with an aggressive policy of rescue angioplasty and early in-hospital revascularization. Outcomes compared favorably with those reported for PPCI trials. The adverse prognosis in older patients with higher TIMI risk score suggests that in those patients alternative initial treatment strategies such as PPCI should be considered.

Background and Aims: The value of multi-detector row computed tomography (MDCT) in routine cardiology practice is uncertain. We examined the applicability of MDCT imaging for the diagnosis of obstructive coronary artery disease in a routine clinical setting. Methods: MDCT scanning (40 slice) was performed in 111 unselected patients referred for invasive coronary angiography (ICA) and findings were compared to an independent quantitative assessment of the ICA on a segmental, vessel and patient basis. Results: Sensitivity and positive predictive value for segmental disease (72.2 and 70.9% respectively, overall) were higher in patients aged ≧60 years and history of disease ≧1 year, whereas specificity and negative predictive value were high in all groups. In the patient-based analysis, sensitivity and positive predictive value (84.7 and 87.8%, respectively) were higher, the latter in keeping with the high-patient prevalence of disease, but specificity and negative predictive value (61.5 and 55.2%) were low. Conclusions: Usefulness of MDCT was significantly influenced by age, duration of coronary artery disease and female gender, and on a patient-based analysis its diagnostic accuracy was not sufficient to replace ICA in a routine clinical setting.

We examined the relations among body mass index (BMI), extent of coronary artery disease, and frequency of high-risk coronary anatomy (HRCA) in 928 consecutive patients who underwent coronary angiography during a 6-month period. HRCA was defined asor=50% stenosis of the left main coronary artery and/or significant 3-vessel coronary artery disease (or=70% narrowing). BMI was classified into 5 subgroups: low (21 kg/m(2)), normal (21 to 24 kg/m(2)), overweight (25 to 29 kg/m(2)), obese (30 to 34 kg/m(2)), and severely obese (or=35 kg/m(2)). Obese patients (BMIor=30 kg/m(2)) were younger (61.4 +/- 10.7 vs 65.3 +/- 11.4 years, p0.0001) and had higher prevalences of hyperlipidemia, systemic hypertension, and diabetes mellitus. HRCA was present less often in obese patients (56 of 245, 23%, vs 250 of 683, 37%, p = 0.0002). Multivariate regression analysis showed that advancing age (p0.0001), male gender (p = 0.007), diabetes mellitus (p = 0.0004), and hyperlipidemia (p = 0.0008) were independent predictors of high-risk anatomy, whereas obesity remained a significant negative independent predictor (p = 0.02). Late (30 to 36 months) mortality was not different between obese (6.9%) and nonobese (8.2%) patients but was significantly higher in patients with HRCA (12.4%) than in those without HRCA (5.6%, p = 0.0003). In conclusion, obese patients who were referred for coronary angiography were younger and had a lower prevalence of HRCA. Obese patients were probably referred for angiography at an earlier stage of their disease, thus explaining the "obesity paradox" in several reports of better short-term outcome in obese patients who undergo cardiac procedures.

The evolution of acute coronary syndromes (ACS) is not always clearly understood, and our understanding has been limited by the absence of serial information regarding the coronary vasculature in these patients. We describe a young patient with an acute inferior wall myocardial infarction in whom repeat multi-detector computed tomographic scanning (MDCT), supported by invasive studies, revealed a transient filling defect in the proximal left anterior descending coronary artery and nonobstructed circumflex and right coronary arteries. New generation 64-slice MDCT scanning provides a new method for visualizing both the coronary lumen and coronary plaque, and may prove to be a useful tool in improving our understanding of the dynamics of ACS. © 2006 Wiley-Liss, Inc.

Background and Aims: While current guidelines recommend a selective invasive approach after low-risk ST-elevation myocardial infarction (STEMI) treated by thrombolysis, based on noninvasive identification of patients with residual or inducible myocardial ischemia, in many instances physicians employ a strategy of routine angiography. The present study was undertaken to reexamine the correlation between noninvasive testing and coronary angiography in patients recovering from uncomplicated STEMI with regard to detection and management of residual infarct artery stenosis and to identify patients with multivessel (MVD) or high-risk coronary disease. Methods: We prospectively performed predischarge exercise testing (ETT) and myocardial perfusion scintigraphy (MPS) prior to routine predischarge coronary angiography in 83/276 consecutive STEMI patients, who after treatment with initial and early thrombolysis, were defined as low risk by ACC/AHA risk classification. Results: ETT was positive for myocardial ischemia in 11/43 (26%) patients with single-vessel disease (SVD) and 11/22 (50%) patients with MVD, but normal or nondiagnostic in the remainder. MPS revealed significant reversible perfusion defects in 13/40 (32%) patients with SVD and 13/22 (59%) patients with MVD. A selective strategy of ETT followed by MPS for nondiagnostic ETT missed residual infarct-related artery stenosis and/or MVD in 31/81 (38%) of the cohort. Among patients who may not otherwise have been referred for angiography, severe (≧70%) residual stenosis of the infarct-related artery was present in 56% and MVD in 16%. Conclusions: Early predischarge ETT and/or MPS had limited sensitivity for the detection of coronary disease in low-risk post-STEMI patients. The study supports a simpler strategy of routine coronary angiography in most patients after low-risk STEMI.

The elderly and very elderly represent an increasing proportion of patients presenting with acute coronary syndromes. This review examines the current literature regarding the presentation and management of acute coronary syndromes in all their aspects and relates the available data to the elderly and very elderly populations. The specific fields relating to presentation and symptoms, pharmacotherapy and interventional and surgical treatment are discussed and the entities of non-ST-elevation and ST-elevation acute coronary syndromes are dealt with individually.

While advances in treatment strategies and pharmacotherapy have produced a dramatic reduction in the mortality of patients with heart failure during the past 15 years, there is still a major challenge to improve patient well being, reduce hospitalizations and reduce mortality further. The prevalence of heart failure is not decreasing, and heart failure is currently a cause for hospitalization in >25% of admissions to internal medicine and cardiology departments. It has recently become apparent that anaemia is present in 20–30% of patients with heart failure, and the severity of anaemia has important implications regarding outcome and prognosis. Anaemia may be due to a number of causes, including iron and vitamin deficiency, insidious blood loss, haemodilution, renal impairment and bone marrow depression with resistance to erythropoietin. In the presence of a damaged heart and often coronary artery disease, anaemia may worsen contractile ability and systolic function, while the necessary volume load and ventricular hypertrophy which accompany anaemia contribute to diastolic dysfunction. Preliminary data show that appropriate treatment of anaemia, based on correction of the underlying cause, with, in most patients, the addition of exogenous erythropoietin and iron therapy, improves ventricular function and clinical status. Treatment of anaemia has opened a new frontier in the management of heart failure. We await the results of ongoing clinical trials for more detailed imformation regarding appropriate haemoglobin targets, choice of medication and dosing and the degree of improvement that may be expected when the issue of anaemia is properly addressed.

BACKGROUND: The CURE study demonstrated the benefit of clopidogrel in patients with non-ST elevation (NSTE) acute coronary syndromes (ACSs), including those undergoing percutaneous coronary intervention (PCI). It did not report the relation between clopidogrel and timing of PCI or, more specifically, the role of clopidogrel in patients managed with an early interventional strategy, the current preferred treatment option for patients with NSTE ACSs. In the present study, we examined the relation between clopidogrel therapy, timing of PCI, and cardiovascular (CV) events in patients participating in the CURE study. METHODS: A total of 12562 patients with NSTE ACSs was randomized in double-blind fashion to clopidogrel or placebo (300 mg loading dose, then 75 mg/d) in addition to aspirin for up to 1 year. We analyzed the data of the 2658 CURE patients undergoing PCI and related the incidence of outcome events (CV death/myocardial infarction [MI]) to timing of PCI after randomization: early ( or = 48 hours to initial hospital discharge, median 6.8 days, n = 1360), and late (after initial hospital discharge, median 47.6 days, n = 928). RESULTS: Clopidogrel showed consistent treatment benefit over the 12-month (mean 9 months) follow-up period irrespective of timing of PCI (relative risk [RR] 0.53 for the early group, RR 0.72 for the intermediate group, RR 0.70 for the late group). After adjustment for propensity to undergo PCI, the greatest treatment benefit of clopidogrel was observed in patients undergoing PCI < 48 hours after randomization (RR 0.45, 95% CI 0.21-0.96, P = .038), although with overlap between groups. The lowest absolute event rate (6.7% CV death/MI) was observed in patients treated with clopidogrel and undergoing PCI within 48 hours. There was no increased risk of major bleeding in the early PCI group. CONCLUSIONS: The benefit of therapy with clopidogrel in addition to aspirin in patients presenting with NSTE ACSs was significant irrespective of the timing of PCI. The combination of clopidogrel and an early (

An anonymous patient perception comprehension and satisfaction questionnaire was sent to 438 patients 1–3 months after they had participated in a clinical cardiovascular trial to examine the level of patient comprehension as perceived by the patient. We compared perceived comprehension in acute (acute myocardial infarction) and chronic (outpatient heart failure) clinical trials. Partially or fully completed questionnaires were received from 220 patients (70 chronic, 150 acute). The findings were similar in the 2 patient groups. Perceived full comprehension (understood most or all) of the trial was reported by 18 (27%) of chronic and 40 (31%) of 129 acute patients, while almost 20% of both groups reported little or no understanding of the trial. The level of comprehension was related to the recollected duration of explanation (p = 0.003 chronic, p < 0.001 acute). Perceived comprehension was not related to the personnel explaining the study (physician or nurse) or to whether the explanation as recollected was oral or written. However, in both acute and chronic patients, the majority (51% chronic; 63% acute) preferentially recalled the oral rather than written explanation of the trial. The very similar findings in the acute and chronic situation suggest that perceived understanding reflects human nature and willingness to be involved in medical issues. Considerable effort should be directed to improve the duration of explanation (particularly oral), if we are to achieve our goal of true informed consent in clinical cardiovascular trials.

We investigated the incidence and determinants of early and late repeat hospitalization for cardiac causes in 378 patients following myocardial revascularization [199 coronary balloon angioplasty (PTCA), 179 coronary bypass surgery (CABG)] in a single cardiovascular center and followed for a median period of 13 years. Data were available for repeat rehospitalization in 91% and for mortality in all. Patients in the upper quartile for repeat hospitalization (≧4 rehospitalizations) were defined as having multiple repeat hospitalizations. In the PTCA cohort, the rehospitalization rate was high (48%) in the first year, partly due to restenosis and to a group of patients who underwent planned repeat angiography, and then 15–26% annually. In the surgical cohort, annual repeat hospitalization was 8–12% during the first 4 years, but increased to a level similar to that in PTCA patients (19–26%) in the second half of the follow-up period. Independent predictors of multiple (≧4) repeat hospitalizations included systemic hypertension (odds ratio 2.4, 95% CI 1.4–4.0), incomplete revascularization (odds ratio 2.0, 95% CI 1.1–3.4) and less extensive (