Drop-out from cardiovascular magnetic resonance in a randomized controlled trial of ST-elevation myocardial infarction does not cause selection bias on endpoints.

BACKGROUND: The extent of selection bias due to drop-out in clinical trials of ST-elevation myocardial infarction (STEMI) using cardiovascular magnetic resonance (CMR) as surrogate endpoints is unknown. We sought to interrogate the characteristics and prognosis of patients who dropped out before acute CMR assessment compared to CMR-participants in a previously published double-blinded, placebo-controlled all-comer trial with CMR outcome as the primary endpoint. METHODS: Baseline characteristics and composite endpoint of all-cause mortality, heart failure and re-infarction after 30 days and 5 years of follow-up were assessed and compared between CMR-drop-outs and CMR-participants using the trial screening log and the Eastern Danish Heart Registry. RESULTS: The drop-out rate from acute CMR was 28% (n = 92). These patients had a significantly worse clinical risk profile upon admission as evaluated by the TIMI-risk score (3.7 (± 2.1) vs 4.0 (± 2.6), p = 0.043) and by left ventricular ejection fraction (43 (± 9) vs. 47 (± 10), p = 0.029). CMR drop-outs had a higher incidence of known hypertension (39% vs. 35%, p = 0.043), known diabetes (14% vs. 7%, p = 0.025), known cardiac disease (11% vs. 3%, p = 0.013) and known renal function disease (5% vs. 0%, p = 0.007). However, the 30-day and 5-years composite endpoint rate was not significantly higher among the CMR drop-out ((HR 1.43 (95%-CI 0.5; 3.97) (p = 0.5)) and (HR 1.31 (95%-CI 0.84; 2.05) (p = 0.24)). CONCLUSION: CMR-drop-outs had a higher incidence of cardiovascular risk factors at baseline, a worse clinical risk profile upon admission. However, no significant difference was observed in the clinical endpoints between the groups.

Assessment of coronary artery disease using coronary computed tomography angiography in patients with aortic valve stenosis referred for surgical aortic valve replacement.

BACKGROUND: In patients referred for aortic valve replacement (AVR) a pre-surgical assessment of coronary artery disease is mandatory to determine the possible need for additional coronary artery bypass grafting. The diagnostic accuracy of coronary computed tomography angiography (coronary CTA) was evaluated in patients with aortic valve stenosis referred for surgical AVR. METHODS: Between March 2008 and March 2010 a total of 181 consecutive patients were included. All patients underwent pre-surgical coronary CTA (64- or 320-detector CT scanner) and invasive coronary angiography (ICA). The analyses were performed blinded to each other. RESULTS: The mean ± SD age of the included patients was 71 ± 9 years and 59% were male. The prevalence of significant coronary artery stenosis >70% by ICA was 36%. Average heart rate during coronary CTA was 65 ± 16 b pm. In a patient based analysis 94% of the patients (171/181) were considered fully evaluable. Coronary CTA had a sensitivity of 68%, a specificity of 91%, a positive predictive value of 81%, and a negative predictive value of 83%. Advanced age, obstructive lung disease, NYHA function class III/IV, and high Agatston score were found to be significantly associated with disagreement between ICA and coronary CTA in univariate analysis. CONCLUSION: In patients with aortic valve stenosis referred for surgical AVR the diagnostic accuracy of coronary CTA to identify significant coronary artery disease is moderate. Coronary CTA may be used successfully in a subset of patients with low age, no chronic obstructive lung disease, NYHA function class

Left ventricular contractile function after distal protection in primary percutaneous coronary intervention: results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial.

BACKGROUND: Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function. METHODS: Patients with STEMI were randomly referred within 12 h for PCI with (N = 312) or without distal protection (N = 314). Left ventricular (LV) contractile function was assessed with echocardiography 8 months after PCI. Global LV myocardial wall motion index (WMI) was calculated as the average wall motion score of all myocardial segments. The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI were also recorded. RESULTS: The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI was 7.1% after distal protection and 5.7% after conventional treatment (p = 0.17). WMI improved by 4.1% at 8 months in patients treated with distal protection compared to patients receiving conventional PCI (p < 0.01). In myocardium supplied by a culprit artery treated by distal protection regional LV function was 9-11% higher than myocardial regions treated conventionally ( p < 0.02). CONCLUSIONS: Routine use of distal protection during primary PCI is associated with a significant improvement in LV contractile function, with no detectable impact on intermediate term clinical outcome.

WITHDRAWN: Quantitative Analysis of Dobutamine-Atropine Stress Echocardiography.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 169-177, . The duplicate article has therefore been withdrawn.

Pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions: no effect on myocardial ischaemia or function.

BACKGROUND: Repeated episodes of myocardial ischaemia may lead to ischaemic preconditioning. This is believed to be mediated by the ATP sensitive potassium channels. OBJECTIVE: To examine the effect of pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions. DESIGN: Double blind, double dummy study. METHODS: 38 patients with a proximal stenosis of the left anterior descending coronary artery and no visible coronary collateral vessels underwent three identical 90 second balloon occlusions, each followed by five minutes of reperfusion. The patients were randomised to pinacidil 25 mg, glibenclamide 10.5 mg, or matching placebo 90 minutes before the start of the procedure. Myocardial ischaemia was measured by continuous monitoring of ECG ST segment changes. Changes in left ventricular function were recorded with a miniature radionuclide detector, and angina was scored on the Borg scale. RESULTS: In all patients the first balloon occlusion led to significant ST segment elevation, a clear decrease in left ventricular ejection fraction, and angina pectoris. This response was not attenuated at the second or third balloon occlusion, either in the placebo group or in the patients pretreated with pinacidil or glibenclamide. CONCLUSIONS: Under the given experimental conditions, this randomised and double blind study did not support the view that the human myocardium has an intrinsic protective mechanism that is activated by short lasting episodes of ischaemia.

Quantitative analysis of dobutamine-atropine stress echocardiography.

AIMS: To investigate the usefulness of fractional area change of entire left ventricular areas obtained from apical views for quantitative analysis of dobutamine-atropine stress echocardiography in the presence of mild to moderately reduced left ventricular function and abnormal intra-thoracic heart motion after coronary artery bypass surgery. METHODS AND RESULTS: Stress echocardiograms from 38 echogenic patients before and 3 months after bypass surgery and from 44 echogenic healthy subjects were analysed. In successfully revascularized patients the fractional area change at peak stress was correlated to the baseline left ventricular ejection fraction (r=0.54, P<0.01), whereas the increase from baseline to peak stress was constant over a wide range of baseline ejection fractions. With respect to identifying the pre-revascularization examination as diseased, the area under the receiver operator characteristics curve based on Delta fractional area change from baseline to peak stress was 0.78 (95% CI 0.55-1.00) indicating moderate accuracy comparable with the results obtained with conventional analysis. CONCLUSION: Fractional area change of entire left ventricular cavity areas is a useful parameter for quantitative analysis of dobutamine-atropine stress echocardiography. The diagnostic properties of the parameter are not offset by moderate reduction in left ventricular function or by surgery-induced abnormal intra-thoracic heart motion.

Quantitative analysis of dobutamine-atropine stress echocardiography by fractional area change.

AIMS: To investigate the usefulness of fractional area change with respect to the diagnosis of coronary artery disease in patients undergoing dobutamine-atropine stress echocardiography. METHODS AND RESULTS: Sixty-eight echogenic patients with a normal left ventricular function referred for coronary angiography underwent dobutamine-atropine stress echocardiography. Measures of fractional area change by segments and by total left ventricular areas were normalized using data from 27 echogenic healthy subjects. The area under the receiver operator characteristics curve indicated a significant diagnostic contribution of fractional area change for both methods (P<0.05) and sensitivity and specificity for predicting significant coronary stenosis were 80% (95% CI 69-91%) and 76% (95% CI 56-97%) for fractional area change of the total left ventricular area of the two chamber view, comparable to results of conventional wall motion analysis. Segmental fractional area change offered no advantages to that of total left ventricular areas with regard to the diagnosis or localization of coronary artery disease. CONCLUSION: Fractional area change of the total left ventricular area is an accurate marker of coronary artery disease and may form a basis for quantitative dobutamine-atropine stress echocardiography analysis provided that reproducible endocardial tracings can be obtained.

Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors.

OBJECTIVES: This study aimed to clarify the role of the angiotensin-converting enzyme (ACE) gene polymorphism in the development of in-stent restenosis. BACKGROUND: In-stent restenosis occurs after treatment of coronary artery stenosis in 12% to 32% of coronary interventions with stents. Experimental and clinical studies have suggested that the deletion/insertion (D/I) polymorphism of the ACE gene plays a role in this. METHODS: Quantitative coronary angiography before, immediately after and six months after stent implantation were compared in 369 patients, in whom D/I typing of the ACE gene was performed. RESULTS: At follow-up we found no differences between the three genotypes in minimal lumen diameter (homozygotes with two deletion alleles in the ACE gene [DD], 2.20 mm; heterozygotes with one deletion and one insertion allele in the ACE gene [DI], 2.19 mm; and homozygotes with two insertion alleles in the ACE gene [II], 2.25 mm). The corresponding diameter stenoses were: DD: 25%, DI: 27%, II: 27% (p = NS), and the frequency of restenosis (>50% diameter stenosis) was: DD: 15.7%, DI: 11.0% and II: 16.4% (p = NS). Logistic regression analysis identified diabetes (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0 to 8.7), lesion length (OR: 1.1, 95% CI: 1.01 to 1.30) and minimal lumen diameter immediately after the intervention (OR: 0.3, 95% CI: 0.14 to 0.85) as predictors of in-stent restenosis. In a post hoc analysis of patients treated versus those not treated with an ACE-inhibitor antagonist or an angiotensin receptor antagonist, we found an increased frequency of in-stent restenosis in the DD genotypes (40% vs. 12%, p = 0.006). CONCLUSIONS: The D/I polymorphism is not an independent predictor of coronary in-stent restenosis in general, but it may be of clinical importance in patients treated with ACE inhibitors or angiotensin receptor antagonists.

Relationship between regional 18F-fluorodeoxyglucose and 13N ammonia uptake in normal myocardium assessed by positron emission tomography: patterns of mismatch and effects of aging.

Increased regional myocardial 18F fluorodeoxyglucose (18FDG) uptake in relation to 13N ammonia (13NH3) uptake--i.e. glucose metabolism-blood flow 'mismatch'--appears to be a strong indicator of myocardial viability in patients with ischemic heart disease (IHD) and regionally reduced contractile function. Reference values of regional 18FDG and 13NH3 uptake have not been determined in healthy subjects with the target age for the development of IHD. We therefore studied healthy middle-aged and old men using positron emission tomography (PET). Twenty-three healthy men aged 51 to 83 years of age were studied. 18FDG and 13NH3 uptake was quantified in 16 myocardial segments with PET and circumferential profile analysis. The relative 18FDG/13NH3 uptake was considerably heterogeneous with 18FDG uptake consistently higher than 13NH3 uptake in the left lateral ventricular wall. This regional 'mismatch' pattern was observed in all subjects, but was most prominent in middle-aged men. The observed age-dependency was the result of a progressive increased in 13NH3 uptake with advancing age in the left ventricular lateral wall. Age-matched reference values of myocardial 18FDG and 13NH3 uptake appears to be important for the discrimination between physiological and pathological glucose metabolism-blood flow mismatch assessed by PET and circumferential profile analysis.

Atrioventricular plane motion during dobutamine-atropine stress echocardiography: the biphasic response in healthy subjects revisited.

This study was undertaken to establish normal values for the systolic atrioventricular plane motion (AVPM) from base to apex during dobutamine-atropine stress echocardiography (DASE) and to compare them with those of patients with coronary artery disease. The AVPM was measured at baseline, low dose and peak dobutamine-atropine infusion in 20 patients referred for coronary angiography and in 20 control subjects. Atrioventricular plane motion was measured at the posterior, anterior, septal, and lateral positions of the mitral annulus in the apical 2- and 4-chamber views by an observer blinded to clinical and angiographic data. In healthy subjects undergoing DASE, AVPM initially increased but subsequently decreased to below baseline values at peak stress. Atrioventricular plane motion at any stage and the changes therein during DASE were within the normal reference interval in the majority of patients. In conclusion, AVPM decreased during DASE in healthy subjects and was not a sensitive marker of coronary artery disease.

Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia.

BACKGROUND: Preserved myocardial oxygen consumption estimated by carbon 11-acetate and positron emission tomography (PET) in myocardial regions with chronic but reversibly depressed contractile function in patients with ischemic heart disease have been suggested to be caused by repeated short episodes of acute myocardial ischemia. To evaluate this hypothesis myocardial 11C-acetate PET imaging was performed before and after acute repetitive myocardial ischemia. METHODS AND RESULTS: In open chest dogs (n = 8), the left anterior descending coronary artery was occluded 4 times for 5 minutes alternating with 5 minutes of reperfusion. Before and after repetitive coronary occlusions, oxygen 15 water/oxygen 15 carbon monoxide (blood flow), and 11C-acetate (oxygen consumption) PET imaging were performed. Left ventricular regional systolic wall thickening was measured with sonomicrometry. Forty-five minutes after the ischemic episodes, systolic ventricular wall thickening was decreased by 90%, whereas myocardial blood flow was reduced by 21% compared with baseline values (P < .05). Ninety minutes after the ischemic episodes, estimated oxygen consumption was unaltered compared with the baseline level despite a sustained 70% decrease in the regional contractile function (P < .05). CONCLUSIONS: Oxygen consumption estimated by 11C-acetate PET imaging is preserved after repeated episodes of acute myocardial ischemia despite a severe impairment of contractile function.

Percutaneous transradial coronary angiography and angioplasty in patients with occlusive atherosclerotic iliofemoral disease.

Not all coronary angiograms can be acquired through the femoral route. The transradial catheterisation procedure in patients with occlusive atherosclerotic iliofemoral disease is described. Transfemoral left-sided cardiac catheterisation was performed in approximately 99.5% of patients referred for coronary angiography, while out of 48 patients in whom transfemoral access was impossible, transradial coronary angiography was successful in 37. With the exception of one, all patients with coronary artery disease had lesions of the right coronary artery, more than 70% had multivessel disease and 14% had stenosis of the left main coronary artery. Ten patients had angioplasty performed during the same procedure. Complications occurred in 5 out of 39 cases, 2 (5%) of these were severe. Although the femoral route was used in more than 99% of an unselected population referred for coronary angiography, it was found that transradial angiography and angioplasty can be performed in patients with occlusive atherosclerotic iliofemoral disease with considerable success and an acceptable complication rate.

Vasodilatation with felodipine in chronic asymptomatic aortic regurgitation.

BACKGROUND: Afterload reduction decreases volume overload on the left ventricle and may thereby delay the need for valve replacement in chronic asymptomatic aortic regurgitation. The aims of this randomized double-blind, placebo-controlled trial were to examine short- and long-term hemodynamic effects of felodipine in chronic asymptomatic aortic regurgitation. METHODS: Sixteen patients were randomly assigned to an intravenous infusion of either felodipine 0. 3 mg or placebo followed by 3 months' treatment with felodipine 10 mg or placebo orally once daily. Magnetic resonance imaging was performed at baseline, immediately after intravenous treatment, and after 3 months of oral treatment. RESULTS: Intravenous felodipine caused a statistically significant reduction in the systemic vascular resistance from (mean +/- SD) 1160 +/- 400 to 970 +/- 320 dynes. s. cm(-5) (P <.05), in the regurgitant volume index from 1.5 +/- 0.8 to 1.3 +/- 0.8 L. min(-1). m(-2) (P <.05), and in the regurgitant fraction from 0.31 +/- 0.15 to 0.26 +/- 0.14 (P <.05). The forward cardiac output index increased significantly from 3.2 +/- 0.9 to 3.5 +/- 0.7 L. min(-1). m(-2) (P <.05). Three months of oral treatment with felodipine caused a corresponding but more pronounced decrease in systemic vascular resistance of 880 +/- 330 dynes. s. cm(-5) (P <.05), regurgitant volume index of 1.2 +/- 0.7 L. min(-1). m(-2) (P <.05), and regurgitant fraction 0.25 +/- 0.11 (P <.05), whereas the forward cardiac output index increased to 3.6 +/- 0.7 L. min(-1). m(-2) (P <.05). No significant changes were found in the placebo group. Left ventricular volumes and ejection fraction remained unaffected by treatment, but compared with the placebo group left ventricular myocardial mass decreased significantly from 137 +/- 24 to 132 +/- 21 g. m(-2) (P <.01). CONCLUSION: In chronic asymptomatic aortic regurgitation, felodipine causes beneficial hemodynamic effects that may postpone the need for valve replacement.

Comparison of methods of fractional area change for detection of regional left ventricular dysfunction.

Three methods for assessment of fractional area change (FAC) and conventional versus cross-sectional segmentation were compared under conditions known to occur frequently during stress echocardiography. Quantitative analysis of 80 echocardiograms obtained from healthy subjects, patients with left ventricular (LV) dysfunction and after coronary artery bypass grafting included segmental and cross-sectional FACs by the centroid method with fixed and floating reference and a method with floating external reference. All segmental and cross-sectional FACs were equally sensitive to LV dysfunction, and segmental FACs failed to accurately predict the location of coronary lesions. The centroid method with floating reference and cross-sectional FACs were the least affected by surgery induced intrathoracic heart motion. In moderate to severe LV dysfunction FAC by the centroid method with floating reference and cross sections were rarely within normal limits. Cross-sectional FACs may prove to be useful in stress echocardiography. For viability studies segmental FAC by fixed reference appears to be the method of choice.

[Cardiac scanning with positron emission tomography--PET. Clinical use and research aspect]. / Hjertescanning med positronemissionstomografi--PET. Klinisk anvendelse og forskningsmaessig betydning.

Assessment of regional myocardial glucose metabolism and regional myocardial perfusion has become possible with positron emission tomography (PET). These parameters are of importance in distinguishing viable from fibrotic myocardium in patients with ischaemic heart disease. PET scanning appears to be the method of choice in these patients, which has led to an increased clinical application of PET as a method usable to select patients with severe heart disease before potential revascularisation. In the present review, PET technology is briefly described, together with an overview of the scientific evidence supporting the clinical application of cardiac PET. Finally, its applications in the fields of pathophysiology and pharmacology are briefly described.

Amlodipine reduces myocardial ischaemia during exercise without compromising left ventricular function in patients with silent ischaemia: a randomised, double-blind, placebo-controlled study.

BACKGROUND: Left ventricular systolic function is reduced during episodes of silent ischaemia in patients with coronary artery disease (CAD). In most normal subjects left ventricular ejection fraction (LVEF) increases at least 5% during exercise whereas LVEF often remains unchanged or decreases in patients with CAD. The anti-ischaemic effect of calcium antagonists is well documented including a capability to reduce exercise-induced electrocardiographic ST-depressions, whereas the effect of these drugs on LV volume changes during exercise in patients with silent ischaemia is unknown. AIM: The aim of this study was to evaluate the effect of amlodipine on rest and exercise LVEF in patients with silent ischaemia. METHODS: Twenty-one patients completed a double-blind placebo-controlled cross-over study. Conventional exercise test and radionuclide cardiographies during exercise were used for determining haemodynamic parameters. RESULTS: Exercise-induced electrocardiographic ST-depressions were reduced in 83% of the patients having ST-deviations during placebo even though 10 patients were already treated with a beta-blocker. Amlodipine did not affect left ventricular systolic function compared to placebo, neither at rest nor during exercise. CONCLUSION: The results indicated that amlodipine is a safe anti-ischaemic drug in patients with silent ischaemia concerning cardiac function.

[Hypertrophic cardiomyopathy]. / Hypertrofisk kardiomyopati.

Hypertrophic cardiomyopathy is a heterogeneous, progressive disease with a variable age of debut. Hypertrophic cardiomyopathy is characterized by myocardial hypertrophy with a bizarre fibre disarray. Angina pectoris, dyspnoea and syncope are the most frequent symptoms. Hypertrophic cardiomyopathy is an important cause of sudden death, especially in children and young adults. The aetiology is genetic in more than 60% of the cases, with an autosomal dominant mode of inheritance. More than 50 different mutations involving six genes have so far been associated with the development of hypertrophic cardiomyopathy. These mutations are located to genes coding for several of the proteins in the cardiac sarcomere. The protein changes seem to compromise contractility as well as sarcomere assembly, thereby secondarily causing compensatory hypertrophy. The management of hypertrophic cardiomyopathy has been markedly improved within the last few years. This emphasizes the importance of determining prognostic markers in each patient. A specific genetic diagnosis may prove to be of major importance.

[Treatment of hypertrophic cardiomyopathy]. / Behandling af hypertrofisk kardiomyopati.

The medical management of hypertrophic cardiomyopathy is reviewed. Four cases of hypertrophic cardiomyopathy are presented, and serve to describe the currently available invasive treatment modalities, i.e. septal myectomy, dual chamber pacing, cardioverter defibrillator implantation and heart transplantation. These different invasive treatments all seem to be symptomatically effective in carefully selected patients, but studies of prognostic effects are not available. Finally, new experimental procedures are presented.