Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study.

Aims: To examine the 3.5 year prognosis of stable coronary artery disease (CAD) as assessed by coronary computed tomography angiography (CCTA) in real-world clinical practice, overall and within subgroups of patients according to age, sex, and comorbidity. Methods and results: This cohort study included 16,949 patients (median age 57 years; 57% women) with new-onset symptoms suggestive of CAD, who underwent CCTA between January 2008 and December 2012. The endpoint was a composite of late coronary revascularization procedure >90 days after CCTA, myocardial infarction, and all-cause death. The Kaplan-Meier estimator was used to compute 91 day to 3.5 year risk according to the CAD severity. Comparisons between patients with and without CAD were based on Cox-regression adjusted for age, sex, comorbidity, cardiovascular risk factors, concomitant cardiac medications, and post-CCTA treatment within 90 days. The composite endpoint occurred in 486 patients. Risk of the composite endpoint was 1.5% for patients without CAD, 6.8% for obstructive CAD, and 15% for three-vessel/left main disease. Compared with patients without CAD, higher relative risk of the composite endpoint was observed for non-obstructive CAD [hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01-1.63], obstructive one-vessel CAD (HR: 1.83; 95% CI: 1.37-2.44), two-vessel CAD (HR: 2.97; 95% CI: 2.09-4.22), and three-vessel/left main CAD (HR: 4.41; 95% CI :2.90-6.69). The results were consistent in strata of age, sex, and comorbidity. Conclusion: Coronary artery disease determined by CCTA in real-world practice predicts the 3.5 year composite risk of late revascularization, myocardial infarction, and all-cause death across different groups of age, sex, or comorbidity burden.

The Western Denmark Cardiac Computed Tomography Registry: a review and validation study.

BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We examined the content, data quality, and research potential of the WDHR-CCTR. METHODS: We retrieved 2008-2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables. RESULTS: By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography performed in patients with symptoms indicative of coronary artery disease. Compared with the Danish National Patient Registry, the overall procedure completeness was 72%. However, an additional medical record review of 282 patients registered in the Danish National Patient Registry, but not in the WDHR-CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%-100%), but was >85% for more than 70% of all variables. Using medical record review of 250 randomly selected patients as reference standard, the positive predictive value for the 19 variables ranged from 89% to 100% (overall 97%), whereas the negative predictive value ranged from 97% to 100% (overall 99%). Stratification by center status showed consistently high positive and negative predictive values for both university (96%/99%) and nonuniversity centers (97%/99%). CONCLUSION: WDHR-CCTR provides ongoing prospective registration of all cardiac CTs performed in Western Denmark since 2008. Overall, the registry data have a high degree of completeness and validity, making it a valuable tool for clinical epidemiological research.

Traditional SCORE-based health check fails to identify individuals who develop acute myocardial infarction.

INTRODUCTION: Atherosclerotic cardiovascular disease (CVD), including acute myocardial infarction (AMI), is caused by well-known risk factors. They constitute important therapeutic targets, but their predictive value is disputed. We evaluated the effectiveness of the risk scoring system (SCORE) and thresholds for pharmacotherapy re-commended in the European guidelines on CVD prevention. MATERIAL AND METHODS: The medical records of 605 consecutive patients hospitalized for a first AMI were reviewed. Patients with pre-existing CVD, diabetes, or incomplete information on risk factors were excluded. Those not treated with statin before AMI were risk stratified based on risk factors. A SCORE ≥ 5% or ≥ 10% was considered to qualify for preventive medication in young adults (age ≤ 60 years) or elderly (age > 60 years), respectively. RESULTS: Before AMI, 40 (9%) used statin. Among non-statin users, only five of the 109 young adults had a SCORE ≥ 5%, and 23 of the 284 elderly had a SCORE ≥ 10%. Among women, only three elderly qualified for treatment. More than four times more patients would have qualified for treatment with the high-risk country chart used in 2011. The incremental value of the novel high-density lipoprotein adjusted SCORE charts was limited. CONCLUSION: Few patients admitted with a first AMI used statin. Among non-statin users, SCORE and the recommended thresholds for pharmacotherapy identified no women and less than one out of ten men who untreated were destined for an AMI before 61 years of age. The preventive potential of a traditional risk factor-based health check is limited. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Objective structured assessment of technical competence in transthoracic echocardiography: a validity study in a standardised setting.

BACKGROUND: Competence in transthoracic echocardiography (TTE) is unrelated to traditional measures of TTE competence, such as duration of training and number of examinations performed. This study aims to explore aspects of validity of an instrument for structured assessment of echocardiographic technical skills. METHODS: The study included 45 physicians with three different clinical levels of echocardiography competence who all scanned the same healthy male following national guidelines. An expert in echocardiography (OG) evaluated all the recorded, de-identified TTE images blindly using the developed instrument for assessment of TTE technical skills. The instrument consisted of both a global rating scale and a procedure specific checklist. Two scores were calculated for each examination: A global rating score and a total checklist score. OG rated ten examinations twice for intra-rater reliability, and another expert rated the same ten examinations for inter-rater reliability. A small pilot study was then performed with focus on content validity. This pilot study included nine physicians who scanned three patients with different pathologies as well as different technical difficulties. RESULTS: Validity of the TTE technical skills assessment instrument was supported by a significant correlation found between level of expertise and both the global score (Spearman 0.76, p<0.0001) and the checklist score (Spearman 0.74, p<0.001). Both scores were able to distinguish between the three levels of competence that were represented in the physician group. Reliability was supported by acceptable inter- and intra-rater values. The pilot study showed a tendency to improved scores with increasing expertise levels, suggesting that the instrument could also be used when pathologies were present. CONCLUSIONS: We designed and developed a structured assessment instrument of echocardiographic technical skills that showed evidence of validity in terms of high correlations between test scores on a normal person and the level of physician competence, as well as acceptable inter- and intra-rater reliability scores. Further studies should, however, be performed to determine the adequate number of assessments needed to ensure high content validity and reliability in a clinical setting.

Changes in blood pressure and systemic vascular resistance do not predict microvascular structure during treatment of mild essential hypertension.

BACKGROUND: Essential hypertension is characterized by small artery remodeling and increased systemic vascular resistance (SVR). We hypothesized that changes in SVR index (SVRI) were associated with measures of small artery structure as reflected by minimum coronary and forearm vascular resistance (C-Rmin and F-Rmin, respectively). Also, we investigated how F-Rmin is related to C-Rmin, coronary flow reserve (CFR), left ventricular mass index (LVMI) and blood pressure (BP). METHOD: Sixty-six never-treated patients with uncomplicated mild essential hypertension had the following measured at baseline: 24-h blood BP, LVMI, CFR and C-Rmin (echocardiography), F-Rmin (forearm plethysmography) and SVRI determined by a gas re-breathing method. After 6 months of antihypertensive therapy administered by the general practitioner, the patients returned for follow-up measurements. RESULTS: Changes in SVRI did not correlate to changes in F-Rmin (r = 0.001, P = 0.98) or C-Rmin (r = 0.13, P = 0.39) but did correlate to changes in CFR (r = 0.30, P = 0.04). Further analysis was performed by assigning the patients into two groups according to the median of drop in F-Rmin. When adjusted in a multivariate model, changes in F-Rmin (-8.1 ±â€Š3.2%) were significantly associated with changes in C-Rmin (-9.3 ±â€Š4.9%) and LVMI (-6.9 ±â€Š1.7%) (P < 0.01), but not to either 24-h BP, SVRI or CFR. CONCLUSION: The results show that changes in neither BP nor SVRI reflected changes in minimum vascular resistance. However, changes in the forearm and coronary microcirculation occurred in parallel. Moreover, we demonstrated that neither BP nor SVRI reduction can predict changes in microvascular structure in hypertension. Thus, direct measurements of microvascular structure are needed to determine whether improvement is obtained.

The relationship between immediate relevant basic science knowledge and clinical knowledge: physiology knowledge and transthoracic echocardiography image interpretation.

Two major views on the relationship between basic science knowledge and clinical knowledge stand out; the Two-world view seeing basic science and clinical science as two separate knowledge bases and the encapsulated knowledge view stating that basic science knowledge plays an overt role being encapsulated in the clinical knowledge. However, resent research has implied that a more complex relationship between the two knowledge bases exists. In this study, we explore the relationship between immediate relevant basic science (physiology) and clinical knowledge within a specific domain of medicine (echocardiography). Twenty eight medical students in their 3rd year and 45 physicians (15 interns, 15 cardiology residents and 15 cardiology consultants) took a multiple-choice test of physiology knowledge. The physicians also viewed images of a transthoracic echocardiography (TTE) examination and completed a checklist of possible pathologies found. A total score for each participant was calculated for the physiology test, and for all physicians also for the TTE checklist. Consultants scored significantly higher on the physiology test than did medical students and interns. A significant correlation between physiology test scores and TTE checklist scores was found for the cardiology residents only. Basic science knowledge of immediate relevance for daily clinical work expands with increased work experience within a specific domain. Consultants showed no relationship between physiology knowledge and TTE interpretation indicating that experts do not use basic science knowledge in routine daily practice, but knowledge of immediate relevance remains ready for use.

Disproportionally impaired microvascular structure in essential hypertension.

BACKGROUND: Increased microvascular resistance and small artery remodelling are key abnormalities in the pathophysiology of essential hypertension. We investigated the relation between the impairment of coronary and forearm minimum vascular resistances (C-Rmin and F-Rmin) and the degree of hypertension. METHOD: Seventy-five never-treated essential hypertension patients with 24-h systolic blood pressure (BP) at least 130 mmHg or diastolic BP at least 80 mmHg were assigned into grade 1 (office BP 140/90-159/99 mmHg) and grade 2 (office BP 160/100-179/109 mmHg) hypertension and compared to normotensive controls (n = 25). The patients were (48 years, 60% men) without cardiovascular disease. C-Rmin and coronary flow reserve (CFR) were derived from flow measurements in the left anterior descending artery using transthoracic echocardiography. F-Rmin was measured using venous occlusion plethysmography. Resting systemic vascular resistance index (SVRI) was measured with a gas rebreathing technique. RESULTS: Compared to normotensive controls: 24-h mean BP was raised 14% in grade 1 essential hypertension and 28% in grade 2 essential hypertension, whereas F-Rmin and C-Rmin were elevated by 58 and 87% in grade 1 essential hypertension and 72 and 125% in grade 2 essential hypertension. C-Rmin and F-Rmin were thus both increased more than expected from the BP level. SVRI and left-ventricular mass were increased proportionally to the BP. CFR was decreased by approximately 30% in both essential hypertension groups. CONCLUSION: The results demonstrate excessive microvascular structural abnormalities in hypertension suggesting microvascular alterations occur early and not just as an adaptation to the BP level. Thus the level of BP elevation does not give an accurate indication of the microvascular involvement and impairment in essential hypertension.

Impact of luminal density on plaque classification by CT coronary angiography.

UNLABELLED: Non-invasive coronary CT angiography (CCTA) has the potential to characterize the composition of non-calcified coronary plaques. CT-density values characterized by Hounsfield Units (HU) may classify non-calcified plaques as fibrous or lipid-rich, but the luminal density caused by the applied contrast material influences HU in the plaques in vitro. The influence of luminal density on HU in non-calcified plaques in vivo is unknown. Hence the purpose of this study was to test whether plaque characterization by CCTA in vivo depends on luminal density. Two CCTA-scans using two different contrast protocols were obtained from 14 male patients with coronary artery disease. The two contrast protocols applied resulted in high and low luminal density. Eleven non- calcified and 13 calcified plaques were identified and confirmed by intravascular ultrasound. Luminal attenuation differed with the two contrast protocols; 326[284;367] vs. 118[103;134] HU (P < 0.00001). In non-calcified plaques mean HU-values was lower 48[28;69] vs. 11[-4;25] HU (P = 0.004) with the low density protocol. As a consequence three out of eleven non-calcified plaques (27%) were reclassified from fibrous (high) to lipid rich (low). For calcified plaques a less pronounced but still significant difference in HU-values was found with the low luminal density. 770[622;919] vs. 675[496;855] HU (P = 0.02). CONCLUSION: Non-calcified plaques can be identified and classified by CCTA. However, the luminal density affects the absolute HU of both non-calcified and calcified plaques. Characterization and classification of non-calcified plaques by absolute CT values therefore requires standardization of contrast protocols.

Increased mortality after dronedarone therapy for severe heart failure.

BACKGROUND: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure. METHODS: In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure. RESULTS: After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group. CONCLUSIONS: In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.)

64-multislice detector computed tomography coronary angiography as potential alternative to conventional coronary angiography: a systematic review and meta-analysis.

AIMS: To evaluate the diagnostic accuracy of 64-slice multi-detector computed tomography coronary angiography (64-SCTA) compared with the standard reference conventional coronary angiography (CCA). METHODS AND RESULTS: Based on a systematic search, 27 studies including 1740 patients were eligible for meta-analyses. Nineteen studies examined native coronary arteries (n = 1,251), four studies examined coronary artery by-pass grafts (CABG) (n = 271), and five studies examined coronary stents (n = 270). Overall 18 920 segments were assessable and 810 (4%) were unassessable. The prevalence of native coronary artery stenosis in per-segment (19 studies) and per-patients (13 studies) populations were 19 and 57.5% respectively. Accuracy tests with 95% confidence intervals comparing 64-SCTA vs. CCA showed that sensitivity, specificity, positive predictive and negative predictive values for native coronary arteries were 86(85-87), 96(95.5-96.5), 83, and 96.5% by per-segment analysis; 97.5(96-99), 91(87.5-94), 93, and 96.5% by per-patient analysis; 98.5(96-99.5), 96(93.5-97.5), 92 and 99% for CABGs; 80(70-88.5), 95(92-97), 80, and 95% for stent restenosis; and 87(86.5-88), 96(95.5-96.5), 83.5, and 97% by overall per-segment analysis. CONCLUSION: The high diagnostic accuracy of 64-SCTA validates this non-invasive technique as a potential alternative to CCA in carefully selected populations suspected for coronary stenosis.

Effects of losartan and captopril on left ventricular systolic and diastolic function after acute myocardial infarction: results of the Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan (OPTIMAAL) echocardiographic substudy.

BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to attenuate adverse remodeling after acute myocardial infarction (AMI), and the same has been suggested for angiotensin II type 1 receptor antagonists in animal models. Therefore the aim of the study was to compare the effects of losartan and captopril on regional systolic, diastolic, and overall left ventricular (LV) function after AMI. METHODS: Two hundred twenty-five patients aged > or =50 years with documented AMI and heart failure and/or LV dysfunction were randomly assigned treatment with either losartan (50 mg/d) or captopril (50 mg 3 times/d). Echocardiography was performed at randomization and after 3 months; echocardiograms were analyzed blinded at the core laboratory. Main outcome measures were changes in wall motion score index (WMSI), E-wave deceleration time (E-DT), and Tei index of overall LV function. RESULTS: WMSI decreased in both groups (losartan 1.58 +/- 0.23 to 1.52 +/- 0.26, P =.009, captopril 1.60 +/- 0.24 to 1.48 +/- 0.22, P <.001), although the decrease was greater in patients allocated to captopril (captopril -0.12 +/- 0.17 vs losartan -0.05 +/- 0.19, P =.007). In both groups E-DT increased, although the increase was significant only in patients treated with captoril (193 +/- 61 ms to 208 +/- 70 ms, P =.05). The change in E-DT was not different between treatment groups (captopril 14 +/- 74 ms vs losartan 7 +/- 80 ms, P =.52). Tei index decreased in both groups (losartan 0.59 +/- 0.13 to 0.55 +/- 0.15, P =.04, captopril 0.62 +/- 0.15 to 0.55 +/- 0.13, P <.001). However, the reduction was significantly greater in patients treated with captopril (captopril -0.08 +/- 0.14 vs losartan -0.03 +/- 0.14, P =.01). CONCLUSION: Losartan and captopril improve systolic and overall LV function after AMI, but the benefit is greater for patients treated with captopril.

Differential postprandial lipoprotein responses in type 2 diabetic men with and without clinical evidence of a former myocardial infarction.

Postprandial lipemia plays an important role in the development of coronary heart disease through an elevation of triglyceride-rich lipoproteins. In type 2 diabetic male subjects, our aim was to compare postprandial lipemia in a high-risk population with former myocardial infarction (MI) with that of a lower risk population free of clinically detectable heart disease. 32 male type 2 diabetic subjects were included in the study. We matched 17 cases with a verified history of MI with 15 controls according to age, BMI, HbA1c, diabetes duration, smoking, and treatment of diabetes. Ongoing metformin, insulin, or lipid lowering pharmacological treatment were exclusion criteria. After a maximal exercise tolerance test and echocardiography, the subjects underwent a hyperinsulinemic, euglycemic clamp and a vitamin A fat loading test. Plasma triglyceride levels in the case group were significantly higher after 360 minutes (4.6 +/- 3.1 vs. 2.8 +/- 1.8 mmol/l, p = 0.04) and 480 minutes (3.6 +/- 2.2 vs. 2.4 +/- 2.4 mmol/l, p = 0.03), as was the incremental Area Under the Curve (iAUC) for the whole period (560 +/- 452 vs. 297 +/- 214 mmol x 480 min./l; p = 0.048). In addition, the retinyl palmitate responses in the chylomicron-fraction from the case group were significantly higher (iAUC 311,502 +/- 194,933 vs. 187,004 +/- 102,928 ng x 480 min./ml; p = 0.035). Type 2 diabetic males with prior MI had higher postprandial triglyceride-rich lipoprotein responses than those without MI, indicating that high responses may be a marker for a high-risk population.

Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) has previously been shown to be associated with insulin resistance and hyperinsulinemia. A beneficial effect of the non-selective beta-blocker carvedilol has been demonstrated in patients with CHF. However, whether the drug affects the insulin sensitivity (S(i)) is unknown. AIMS: To investigate whether treatment with carvedilol alters the S(i) in patients with CHF during a prospective, double-blinded, placebo-controlled study. METHODS AND RESULTS: The patients were randomized to receive either carvedilol (n=29) or matched placebo (n=17). Insulin and glucose responses were measured during a 0.3 g/kg intravenous glucose tolerance test, and S(i) was calculated according to Bergman's Minimal Model. Baseline S(i) values correlated significantly with body mass index (r=-0.42, P=0.002), plasma urate (r=-0.42, P=0.002), plasma HDL-cholesterol (r=0.39, P=0.003), maximal oxygen uptake (r=0.35, P=0.009), plasma triglycerides (r=-0.34, P=0.01) and weight (r=-0.29, P=0.03). During the study the insulin sensitivity was unchanged in the carvedilol group compared with placebo (2.63+/-1.45 to 2.38+/-1.64 vs. 2.81+/-2.36 to 2.48+/-1.84x10(-4) min(-1)/mUl(-1), P=0.83). CONCLUSION: Additional treatment with carvedilol is neutral with regard to influence the insulin sensitivity in patients with mild to moderate CHF.

Effect of carvedilol on microcirculatory and glucose metabolic regulation in patients with congestive heart failure secondary to ischemic cardiomyopathy.

In a randomized (2:1), double-blinded design study, we studied 25 patients with congestive heart failure (66 +/- 9 years, ejection fraction 30 +/- 7%) before and after 23-week treatment with the beta blocker carvedilol 25 mg twice daily (n = 17) or placebo (n = 8) in addition to standard therapy. Using dynamic positron emission tomography, myocardial perfusion at rest and perfusion reserve after dipyridamole (0.56 mg/kg/min) were measured. Myocardial glucose uptake and plasma levels of catecholamines were also estimated. Carvedilol treatment reduced the rate-pressure product (8,781 +/- 2,672 vs 6,342 +/- 1,346, p <0.01) and improved ejection fraction (29 +/- 7% vs 37 +/- 11%, p <0.001), whereas no changes were observed in the control group. Perfusion at rest was unchanged in the placebo group (0.81 +/- 0.17 vs 0.86 +/- 0.23 ml/g/min, p = NS), whereas the carvedilol-treated group showed a significant reduction (0.88 +/- 0.26 vs 0.75 +/- 0.16 ml/g/min, p <0.05). Dipyridamole-induced hyperemia was significantly reduced after carvedilol treatment (1.51 +/- 0.45 vs 1.31 +/- 0.51 ml/g/min, p <0.001), whereas myocardial perfusion reserve was unaltered. Carvedilol did not alter myocardial glucose uptake (0.33 +/- 0.14 vs 0.32 +/- 0.12 micromol/g/min, p = NS) or the plasma catecholamines levels. We therefore conclude that in patients with congestive heart failure, carvedilol reduced resting and hyperemic perfusion. No effect on glucose uptake or catecholamine levels was observed. The reduced perfusion at rest must reflect reduced perfusion demand and thereby a higher threshold for myocardial ischemia and protection against myocardial damage or malignant arrhythmia. These effects may serve as a pathophysiologic explanation for the reduced mortality in patients with congestive heart failure who receive carvedilol.