Ernst E. van der Wall

Cardiac computed tomography and myocardial perfusion scintigraphy for risk stratification in asymptomatic individuals without known cardiovascular disease: a position statement of the Working Group on Nuclear Cardiology and Cardiac CT of the European Society of Cardiology

Cardiovascular events remain one of the most frequent causes of mortality and morbidity worldwide. The majority of cardiac events occur in individuals without known coronary artery disease (CAD) and in low- to intermediate-risk subjects. Thus, the development of improved preventive strategies may substantially benefit from the identification, among apparently intermediate-risk subjects, of those who have a high probability for developing future cardiac events. Cardiac computed tomography and myocardial perfusion scintigraphy (MPS) by single photon emission computed tomography may play a role in this setting. In fact, absence of coronary calcium in cardiac computed tomography and inducible ischaemia in MPS are associated with a very low rate of major cardiac events in the next 3-5 years. Based on current evidence, the evaluation of coronary calcium in primary prevention subjects should be considered in patients classified as intermediate-risk based on traditional risk factors, since high calcium scores identify subjects at high-risk who may benefit from aggressive secondary prevention strategies. In addition, calcium scoring should be considered for asymptomatic type 2 diabetic patients without known CAD to select those in whom further functional testing by MPS or other stress imaging techniques may be considered to identify patients with significant inducible ischaemia. From available data, the use of MPS as first line testing modality for risk stratification is not recommended in any category of primary prevention subjects with the possible exception of first-degree relatives of patients with premature CAD in whom MPS may be considered. However, the Working Group recognizes that neither the use of computed tomography for calcium imaging nor of MPS have been proven to significantly improve clinical outcomes of primary prevention subjects in prospective controlled studies. This information would be crucial to adequately define the role of imaging approaches in cardiovascular preventive strategies.

Effects of a new calcium antagonist, mibefradil (Ro 40–5967), on silent ischemia in patients with stable chronic angina pectoris: A multicenter placebo-controlled study

OBJECTIVES The purpose of this study was to evaluate the effects of mibefradil (Ro 40-5967) on the frequency and duration of episodes of asymptomatic ischemia in patients with stable angina pectoris and to determine the most efficient single therapeutic dose of this drug. BACKGROUND Mibefradil is a novel calcium channel antagonist that shows a high bioavailability, induces no reflex tachycardia and has no negative inotropic effects. METHODS In a multicenter, double-blind, placebo-controlled, parallel-design trial, 126 patients with chronic stable angina pectoris were studied. After 1 week of a placebo run-in period, patients were randomized to receive 25, 50, 100, 150 mg of mibefradil or placebo for 2 weeks. Ambulatory 48-h electrocardiographic (ECG) monitoring was performed at the end of both the placebo run-in period and the active treatment period. RESULTS Compared with placebo, mibefradil was associated with significantly less ischemia as manifested during ambulatory ECG monitoring. In the 150- and 100-mg groups, respectively, the drug resulted in a 73% and 63% reduction in the frequency of episodes of ST segment depression and a 78% and 58% reduction in the total duration of ST segment depression. Highly significant linear dose-response relations were present across all treatment groups for ischemic episodes and ischemia duration (p < 0.001). Electrocardiographic abnormalities related to treatment were first-degree atrioventricular block, sinus bradycardia and short Wenckebach episodes, observed during sleep on Holter monitoring. All ECG events were dose related. CONCLUSIONS Mibefradil is a new, safe, well tolerated and very effective dose-dependent anti-ischemic calcium channel antagonist.

Quantitative analysis of cardiovascular MR images.

The diagnosis of cardiovascular disease requires the precise assessment of both morphology and function. Nearly all aspects of cardiovascular function and flow can be quantified nowadays with fast magnetic resonance (MR) imaging techniques. Conventional and breath-hold cine MR imaging allow the precise and highly reproducible assessment of global and regional left ventricular function. During the same examination, velocity encoded cine (VEC) MR imaging provides measurements of blood flow in the heart and great vessels. Quantitative image analysis often still relies on manual tracing of contours in the images. Reliable automated or semi-automated image analysis software would be very helpful to overcome the limitations associated with the manual and tedious processing of the images. Recent progress in MR imaging of the coronary arteries and myocardial perfusion imaging with contrast media, along with the further development of faster imaging sequences, suggest that MR imaging could evolve into a single technique (‘one stop shop’) for the evaluation of many aspects of heart disease. As a result, it is very likely that the need for automated image segmentation and analysis software algorithms will further increase. In this paper the developments directed towards the automated image analysis and semi-automated contour detection for cardiovascular MR imaging are presented.

Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy: Magnetic resonance imaging versus echocardiography

To compare the diagnostic value of spin-echo magnetic resonance (MR) imaging and transthoracic echocardiography in quantitative assessment of the extent of hypertrophy in patients with hypertrophic cardiomyopathy (HCM), we examined 52 consecutive patients with HCM. The Spirito-Maron and Wigle hypertrophy scores were calculated with wall thickness measurements obtained by both imaging modalities. MR imaging yielded complete assessment of anatomic features and allowed calculation of hypertrophy scores in 49 patients (94%). Adequate echocardiograms were obtained in 33 patients (63%) and correlated well with MR imaging for wall thickness measurements and for determination of the two hypertrophy scores (both r> 0.9). MR imaging provided additional information not available by echocardiography in 16 patients (31%). We conclude that the Spirito-Maron and Wigle hypertrophy scores correlated well between echocardiography and MR imaging. Because echocardiography was of insufficient quality for calculating adequate hypertrophy scores in 19 (37%) patients, MR imaging provided the most comprehensive diagnostic information in patients with HCM.

Diagnostic performance of non-invasive multidetector computed tomography coronary angiography to detect coronary artery disease using different endpoints: detection of significant stenosis vs. detection of atherosclerosis.

AIMS The positive predictive value of multidetector computed tomography angiography (CTA) for detecting significant stenosis remains limited. Possibly CTA may be more accurate in the evaluation of atherosclerosis rather than in the evaluation of stenosis severity. However, a comprehensive assessment of the diagnostic performance of CTA in comparison with both conventional coronary angiography (CCA) and intravascular ultrasound (IVUS) is lacking. Therefore, the aim of the study was to systematically investigate the diagnostic performance of CTA for two endpoints, namely detecting significant stenosis (using CCA as the reference standard) vs. detecting the presence of atherosclerosis (using IVUS as the reference of standard). METHODS AND RESULTS A total of 100 patients underwent CTA followed by both CCA and IVUS. Only those segments in which IVUS imaging was performed were included for CTA and quantitative coronary angiography (QCA) analysis. On CTA, each segment was evaluated for significant stenosis (defined as ≥ 50% luminal narrowing), on CCA significant stenosis was defined as a stenosis ≥ 50%. Second, on CTA, each segment was evaluated for atherosclerotic plaque; atherosclerosis on IVUS was defined as a plaque burden of ≥ 40% cross-sectional area. CTA correctly ruled out significant stenosis in 53 of 53 (100%) patients. However, nine patients (19%) were incorrectly diagnosed as having significant lesions on CTA resulting in sensitivity, specificity, positive, and negative predictive values of 100, 85, 81, and 100%. CTA correctly ruled out the presence of atherosclerosis in 7 patients (100%) and correctly identified the presence of atherosclerosis in 93 patients (100%). No patients were incorrectly classified, resulting in sensitivity, specificity, positive, and negative predictive values of 100%. Conclusions The present study is the first to confirm using both CCA and IVUS that the diagnostic performance of CTA is superior in the evaluation of the presence or the absence of atherosclerosis when compared with the evaluation of significant stenosis.

Vitamin D receptor: a new risk marker for clinical restenosis after percutaneous coronary intervention

Objective: Restenosis is the main drawback of percutaneous coronary intervention (PCI). Inherited factors may explain part of the risk of restenosis. Recently, the vitamin D receptor (VDR) has been shown to be involved not only in bone metabolism but also in modulating immune responses and cell proliferation. Since the inflammatory response is implicated in restenosis, VDR-gene variants could therefore contribute to the risk of restenosis. Methods/results: Systematic genotyping for 15 haplotype tagging single-nucleotide polymorphisms (SNPs) of the VDR gene was performed with the high throughput TaqMan allelic discrimination assays in the Genetic Determinants of Restenosis (GENDER) population. A haplotype-based survival analysis revealed an association of haplotypes in blocks 2, 3 and 4 of the VDR-gene with the risk of clinical restenosis (p-values 0.01, 0.04 and 0.02 respectively). After adjustment for clinical risk factors for restenosis, the individual effect of the block 2 AA haplotype (p = 0.011) persisted. Conclusions: The present study indicates that VDR plays a role in restenosis after PCI. Therefore, VDR genotype may be used as risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice.

Coronary vasomotion in patients with syndrome X : Evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min−1·100 g−1; group B, 124±30 ml·min−1·100 g−1 normal subjects, 105±21 ml·min−1·100 g−1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Combined non-invasive anatomical and functional assessment with MSCT and MRI for the detection of significant coronary artery disease in patients with an intermediate pre-test likelihood

Objectives To compare magnetic resonance myocardial perfusion imaging (MRI) with anatomical assessment by multislice computed tomography (MSCT) coronary angiography and conventional coronary angiography. Design and patients In this prospective study, 53 patients (60% male, average age 57±9 years, 83% intermediate pre-test likelihood) underwent 1.5 T MRI, 64-slice MSCT and conventional coronary angiography. Main outcome measures The presence of significant stenosis (≥50% luminal narrowing) was determined on MSCT and conventional coronary angiography. Ischaemia on MRI was defined as a stress perfusion abnormality in the absence of delayed contrast enhancement. Results A significant stenosis was seen on MSCT in 15 (28%) patients, while ischaemia on MRI was seen in 19 (36%). In the 38 patients without significant stenosis on MSCT, normal perfusion was seen in 29 (76%). In patients with a significant stenosis on MSCT, ischaemia was seen in 10 (67%). In all patients without significant stenosis on MSCT and normal perfusion on MRI (n=29), significant stenosis was absent on conventional coronary angiography. All patients with both MSCT and MRI abnormal (n=10) had significant stenoses on conventional coronary angiography. Conclusion The anatomical and functional data obtained with MSCT and MRI are complementary for the assessment of coronary artery disease. These findings support the sequential or combined assessment of anatomy and function.

Diagnosis and management of anomalous origin of the right coronary artery from the left coronary sinus.

The anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva coursing between the aorta and the pulmonary artery or right ventricular outflow tract, is considered a potentially fatal abnormality which may require surgery. However, diagnosing the correct course with coronary arteriography may be difficult. Fast gradient echo magnetic resonance (MR) imaging can be helpful to identify and confirm the course of aberrant coronary arteries and their relationship to the surrounding tissue. In this study, diagnostic procedures and management are described of four patients in whom the RCA originated from the left sinus of Valsalva. Although reported as investigational by the Task Force document on MR imaging by the European Society of Cardiology we are of the opinion that MR coronary angiography may have an important future role in the assessment of anomalous coronary arteries.

Determinants of recurrent ventricular arrhythmia or death in 300 consecutive patients with ischemic heart disease who experienced aborted sudden death: data from the Leiden out-of-hospital cardiac arrest study.

Objective: Evaluation of the relation between clinical characteristics and incidence of recurrent ventricular arrhythmias (VAs) or death during long‐term follow‐up in a cohort of 300 consecutive ischemic heart disease (IHD) patients who had survived an episode of sudden cardiac arrest (SCA).