COVID-19-mediated patient delay caused increased total ischaemic time in ST-segment elevation myocardial infarction.

BACKGROUND: The current study aimed to evaluate changes in treatment delay and outcome for ST-segment elevation myocardial infarction (STEMI) in the Netherlands during the first coronavirus disease 2019 (COVID-19) outbreak, thereby comparing regions with a high and low COVID-19 hospitalisation rate. METHODS: Clinical characteristics, STEMI timing variables, 30-day all-cause mortality and cardiovascular complications of all consecutive patients admitted for STEMI from 1 January to 30 June in 2020 and 2019 to six hospitals performing a high volume of percutaneous coronary interventions were collected retrospectively using data from the Netherlands Heart Registry, hospital records and ambulance report forms. Patient delay, pre-hospital delay and door-to-balloon time before and after the outbreak of COVID-19 were compared to the equivalent periods in 2019. RESULTS: A total of 2169 patients were included. During the outbreak median total treatment delay significantly increased (2 h 51 min vs 2 h 32 min; p = 0.043) due to an increased patient delay (1 h 20 min vs 1 h; p = 0.030) with more late presentations > 24 h (1.1% vs 0.3%) in 2020. This increase was particularly evident during the peak phase of COVID-19 in regions with a high COVID-19 hospitalisation rate. During the peak phase door-to-balloon time was shorter (38 min vs 43 min; p = 0.042) than in 2019. All-cause 30-day mortality was comparable in both time frames (7.8% vs 7.3%; p = 0.797). CONCLUSIONS: During the outbreak of COVID-19 patient delay caused an increase in total ischaemic time for STEMI, with a more pronounced delay in high-endemic regions, stressing the importance of good patient education during comparable crisis situations.

Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.

BACKGROUND AND PURPOSE: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. METHODS: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. RESULTS: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. CONCLUSION: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.

Association between public media and trends in new acute coronary syndrome presentations during the first COVID­19 wave in the Netherlands.

BACKGROUND: We aimed to evaluate the association between public media and trends in new presentations of acute coronary syndrome (ACS) during the first wave of the coronavirus disease 2019 (COVID­19) in the Netherlands. METHODS: New ACS presentations per week in 73 hospitals during the first half of 2019 and 2020 were retrieved from the national organisation Dutch Hospital Data and incidence rates were calculated. Stratified analyses were performed by region, type of ACS and patient characteristics. RESULTS: After the first confirmed COVID­19 case and during lockdown, numbers declined by up to 41% (95% confidence interval (CI): 36-47%) compared to 2019. This reduction was more pronounced for non-ST-segment elevation myocardial infarction (NSTEMI) (48%; 95% CI: 39-55%) and unstable angina (UA; 50%; 95% CI: 40-59%) than for STEMI (34%; 95% CI: 23-43%). There was no association between ACS and COVID­19 incidence rate per region. After the steep decline, a public campaign encouraged patients not to postpone hospital visits. Numbers then increased, without a rebound effect. Trends were similar irrespective of sex, age or socio-economic status. During the outbreak, compared to coronary artery bypass graft procedures, relatively more (acute) percutaneous coronary interventions for NSTEMI and UA were performed. CONCLUSION: New ACS presentations decreased by up to 41%. Lockdown measures and public campaigns, rather than COVID­19 incidence, were associated with significant changes in new ACS presentations. Even though causality cannot be established, this emphasises the role of the public media and healthcare organisations in informing patients to prevent underdiagnoses of ACS and associated health damage.

How often and to what extent do admitted COVID-19 patients have signs of cardiac injury?

BACKGROUND: COVID-19 can cause myocardial injury in a significant proportion of patients admitted to the hospital and seems to be associated with worse prognosis. The aim of this review was to study how often and to what extent COVID-19 causes myocardial injury and whether this is an important contributor to outcome with implications for management. METHODS: A literature search was performed in Medline and Embase. Myocardial injury was defined as elevated cardiac troponin (cTn) levels with at least one value > 99th percentile of the upper reference limit. The primary outcome measure was mortality, whereas secondary outcome measures were intensive care unit (ICU) admission and length of hospital stay. RESULTS: Four studies and one review were included. The presence of myocardial injury varied between 9.6 and 46.3%. Myocardial injury was associated with a higher mortality rate (risk ratio (RR) 5.54, 95% confidence interval (CI) 3.48-8.80) and more ICU admissions (RR 3.78, 95% CI 2.07-6.89). The results regarding length of hospital stay were inconclusive. CONCLUSION: Patients with myocardial injury might be classified as high-risk patients, with probably a higher mortality rate and a larger need for ICU admission. cTn levels can be used in risk stratification models and can indicate which patients potentially benefit from early medication administration. We recommend measuring cTn levels in all COVID-19 patients admitted to the hospital or who deteriorate during admission.

Long-term prognostic value of quantitative myocardial perfusion in patients with chest pain and normal coronary arteries.

BACKGROUND: Patients with chest pain and no obstructive coronary artery disease have shown a high incidence of major adverse cardiovascular events (MACE). We evaluated the role of absolute myocardial perfusion quantification in predicting all-cause mortality and MACE during long-term follow-up in this group of patients. METHODS: We studied 79 patients who underwent Nitrogen-13 ammonia PET for quantification of global myocardial blood flow (MBF) and myocardial flow reserve (MFR) due to suspected impaired myocardial perfusion. Patients with coronary artery disease (i.e., > 30% stenosis in one or more coronary arteries) were excluded. We assessed all-cause mortality and MACE. MACE was defined as the composite incidence of death, myocardial infarction (MI), or hospitalization due to heart failure. RESULTS: Median follow-up was 8 (IQR: 3-14) years. Univariate Cox regression showed that only MFR (P = 0.01) was a predictor of all-cause mortality. Univariate Cox regression analysis showed that both MFR and Stress MBF were predictors of the composite endpoint of MACE (P < 0.001 and P = 0.01, respectively). CONCLUSION: Quantitative assessment of myocardial perfusion may predict all-cause mortality and MACE in patients with chest pain and normal coronary arteries in the long-term follow-up.

Calcification as a risk factor for rupture of abdominal aortic aneurysm.

OBJECTIVES: Abdominal aortic aneurysm (AAA) is a major cause of death in developed countries. The AAA diameter is still the only validated prognostic measure for rupture, and therapeutic interventions are initiated accordingly. This still leads to unnecessary interventions in some cases or unidentified impending ruptures. Vascular calcification has been validated abundantly as a risk factor in the cardiovascular field and may strengthen the rupture risk assessment of the AAA. With this study we aim to assess the correlation between AAA calcification and rupture risk in a retrospective unmatched case-control population. METHODS: A database of 334 AAA patients was evaluated. Three groups were formed: elective (eAAA; n = 233), ruptured (rAAA; n = 73) and symptomatic non-ruptured (sAAA; n = 28) AAA patients. The Abdominal Aortic Calcification-8 score (AAC-8) was used to measure the severity of vascular calcification. RESULTS: The AAA diameter (61 ± 12 mm vs. 74 ± 21 mm; p < .001) and AAC-8 score (3.4 ± 2 points vs. 4.9 ± 2.3 points; p < .001) of the eAAA and the combined rAAA and sAAA groups, respectively, were significantly different after univariate analysis. Multivariate analysis showed that larger AAA diameter (odds ratio [OR]: 1.048/mm increase; 95% confidence interval [CI]: 1.042-1.082; p < .001) and a higher AAC-8 score (OR: 1.34/point increase; 95% CI: 1.19-1.53; p < .001) were significantly associated with development into a sAAA or rAAA. Peripheral artery disease was significantly correlated to eventual elective treatment (OR: 0.39; 95% CI: .15-1; p = .049). CONCLUSION: This study suggests a trend of an increased degree of calcification in symptomatic or even ruptured AAA patients compared with elective AAA patients.

Prevalence of severe subclinical coronary artery disease on cardiac CT and MRI in patients with extra-cardiac arterial disease.

OBJECTIVE: Patients with extra-cardiac arterial disease (ECAD) are at high risk of coronary artery disease (CAD). Prevalence of silent, significant CAD in patients with stenotic or aneurysmal ECAD was examined. Early detection and treatment may reduce CAD mortality in this high-risk group. MATERIALS AND METHODS: ECAD patients without cardiac complaints underwent computed tomography (CT) for calcium scoring, coronary CT angiography (cCTA) if calcium score was 1,000 or under, and adenosine perfusion magnetic resonance imaging (APMR) if there was no left main stenosis. Significant CAD was defined as calcium score over 1,000, cCTA-detected coronary stenosis of at least 50% lumen diameter, and/or APMR-detected inducible myocardial ischemia. In cases of left main stenosis (or equivalent) or myocardial ischemia, patients were referred to a cardiologist. RESULTS: The prevalence of significant CAD was 56.8% (95% CI 47.5 to 66.0). One-hundred and eleven patients were included. Eighty-four patients (76%) had stenotic ECAD, and 27 (24%) had aneurysmal disease. In patients with stenotic ECAD, significant coronary stenosis was present in 32 (38%) and inducible ischemia in eight (12%). Corresponding results in aneurysmal ECAD were eight (30%) and two (11%), respectively (p for difference >.05). Sixteen (19%) patients with stenotic and six (22%) with aneurysmal ECAD were referred to a cardiologist, with subsequent cardiac intervention in seven (44%) and three (50%), respectively (both p >.05). CONCLUSIONS: Patients with stenotic or aneurysmal ECAD have a high prevalence of silent, significant CAD.

Myocardial perfusion reserve compared with peripheral perfusion reserve: a [13N]ammonia PET study.

INTRODUCTION: [13N]ammonia PET allows quantification of myocardial perfusion. The similarity between peripheral flow and myocardial perfusion is unclear. We compared perfusion flow in the myocardium with the upper limb during rest and adenosine stress [13N]ammonia PET to establish whether peripheral perfusion reserve (PPR) correlates with MPR. METHODS: [13N]ammonia myocardial perfusion PET-scans of 58 patients were evaluated (27 men, 31 women, age 64 ± 13 years) and were divided in four subgroups: patients with coronary artery disease (CAD, n = 15), cardiac syndrome X (SX, n = 14), idiopathic dilating cardiomyopathy (DCM, n = 16), and normal controls (NC, n = 13). Peripheral limb perfusion was measured in the muscular tissue of the proximal upper limb and quantified through a 2-tissue-compartment model and the PPR was calculated (stress/rest ratio). MPR was also calculated by a 2-tissue-compartment model. The PPR results were compared with the MPR findings. RESULTS: Mean myocardial perfusion increased significantly in all groups as evidenced by the MPR (CAD 1.99 ± 0.47; SX 1.39 ± 0.31; DCM 1.72 ± 0.69; NC 2.91 ± 0.78). Mean peripheral perfusion also increased but not significantly and accompanied with great variations within and between groups (mean PPR: CAD 1.30 ± 0.79; SX 1.36 ± 0.71; DCM 1.60 ± 1.22; NC 1.27 ± 0.63). The mean difference between PPR and MPR for all subpopulations varied widely. No significant correlations in flow reserve were found between peripheral and myocardial microcirculatory beds in any of the groups (Total group: r = -0.07, SEE = 0.70, CAD: r = 0.14, SEE = 0.48, SX: r = 0.17, SEE = 0.30, DCM: r = -0.11, SEE = 0.71, NC: r = -0.19, SEE = 0.80). CONCLUSION: No correlations between myocardial and peripheral perfusion (reserve) were found in different patient populations in the same PET session. This suggests a functional difference between peripheral and myocardial flow in the response to intravenously administered adenosine stress.

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. beta-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance. METHODS: Patients with newly diagnosed IDC underwent Positron Emission Tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dipyridamole stress), and (18)F-fluoro-deoxyglucose as a metabolism tracer, and a dobutamine stress MRI. MRI and PET were repeated 6 months after maximal beta-blocker therapy. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17 segment-model. Functional response to beta-blocker therapy was assigned as a stable or improved LVEF or diminished LVEF. RESULTS: Sixteen patients were included (age 47.9 +/- 11.5 years; 12 males, LVEF 28.6 +/- 8.4%). Seven patients showed improved LVEF (9.7 +/- 3.1%), and nine patients did not show improved LVEF (-3.4 +/- 3.9%). MPR improved significantly in responders (1.56 +/- .23 to 1.93 +/- .49, P = .049), and MPR decreased in non-responders; however, not significantly (1.98 +/- .70 to 1.61 +/- .28, P = .064), but was significantly different between both groups (P = .017) after beta-blocker therapy. A significant correlation was found between change in perfusion reserve and change in LVEF: a decrease in perfusion reserve was associated with a decrease in LVEF and vice versa. Summed rest score of wall motion in responders improved from 26 to 21 (P = .022) whereas in non-responders no change was observed from 26 to 25) (P = ns). Summed stress score of wall motion in responders improved from 23 to 21 (P = .027) whereas in non-responders no change was observed from 27 to 26) (P = ns). CONCLUSION: In IDC patients, global as well as regional improvement after initiation of beta-blocker treatment is accompanied by an improvement in regional perfusion parameters. On the other hand in IDC patients with further left ventricular function deterioration after initiation of beta-blocker therapy this is accompanied by a decrease in perfusion reserve.

Nuclear imaging in cardiac amyloidosis.

Amyloidosis is a disease characterized by depositions of amyloid in organs and tissues. It can be localized (in just one organ) or systemic. Cardiac amyloidosis is a debilitating disease and can lead to arrhythmias, deterioration of heart function and even sudden death. We reviewed PubMed/Medline, without time constraints, on the different nuclear imaging modalities that are used to visualize myocardial amyloid involvement. Several SPECT tracers have been used for this purpose. The results with these tracers in the evaluation of myocardial amyloidosis and their mechanisms of action are described. Most clinical evidence was found for the use of (123)I-MIBG. Myocardial defects in MIBG activity seem to correlate well with impaired cardiac sympathetic nerve endings due to amyloid deposits. (123)I-MIBG is an attractive option for objective evaluation of cardiac sympathetic level and may play an important role in the indirect measurement of the effect of amyloid myocardial infiltration. Other, less sensitive, options are (99m)Tc-aprotinin for imaging amyloid deposits and perhaps (99m)Tc-labelled phosphate derivatives, especially in the differential diagnosis of the aetiology of cardiac amyloidosis. PET tracers, despite the advantage of absolute quantification and higher resolution, are not yet well evaluated for the study of cardiac amyloidosis. Because of these advantages, there is still the need for further research in this field.

Visualization of anomalous coronary arteries on dual-source computed tomography.

The purpose of this study is to assess the capability of dual-source computed tomography (DSCT) in evaluating coronary artery anomalies. Early detection and evaluation of coronary artery anomalies is essential because of their potential association with myocardial ischemia and sudden death. In 16 patients (12 men, mean age 50 +/- 14 years), anomalous coronary arteries were detected on contrast-enhanced DSCT in a patient cohort of 230 individuals (incidence of 7%). Six different types of anomalies were diagnosed (three fistula, four anomalies of the circumflex artery, four anomalous right coronary arteries, three anomalies of the left coronary artery, one absent left main coronary artery, and one left coronary artery arising from the pulmonary trunk). Of the 16 patients, 10 also underwent conventional coronary angiography (CAG). Retrospective evaluation of the CAGs by an experienced interventional cardiologist resulted in a precise diagnosis in 50% of patients. With DSCT, sufficient image quality and exact visualization of the aberrant anatomy were achieved in all patients. Therefore, DSCT seems to be an accurate diagnostic tool for examining the precise origin, course, and shape of aberrant coronary arteries.

Clinical relevance of advanced glycation endproducts for vascular surgery.

Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery.

Application of PET/SPECT imaging in vascular disease.

BACKGROUND: Nuclear medicine imaging differs from other imaging modalities by showing physiological processes instead of anatomical details. OBJECTIVE: To describe the current applications of positron emission tomography (PET) and single photon emission computed tomography (SPECT) as a diagnostic tool for vascular disease as relevant to vascular surgeons. METHODS: A literature search identified articles focussing on vascular disease and PET or SPECT using the Pubmed database. Manual cross referencing was also performed. RESULTS: PET and SPECT may be used to assess plaque vulnerability, biology of aneurysm progression, prosthetic graft infection, and vasculitis. The ability to combine computerized tomography scanning or magnetic resonance imaging with PET or SPECT adds detailed anatomical information and enhances the potential of nuclear medicine imaging in the investigation of vascular disease. DISCUSSION: Considerable further information will be needed to define whether and where PET or SPECT will fit in a clinical strategy. The necessary validation studies represent an exciting challenge for the future but also may require the development of interdisciplinary imaging groups to integrate expertise and optimize nuclear diagnostic potential.

Mechanisms involved in symptomatic myocardial bridging: Value of sequential testing for endothelial function, flow reserve measurements and dobutamine stress angiography.

BACKGROUND: In patients with extensive myocardial bridging, evaluation of its clinical significance remains a challenge. HYPOTHESIS: Sequential invasive testing is feasible and gives more insight into the pathophysiological mechanism of bridging-related angina. METHODS: Twelve patients with chest pain, proven ischaemia and extensive myocardial bridging were assessed. Myocardial bridging was evaluated at rest, during intracoronary acetylcholine infusion, through coronary flow velocity and flow reserve measurements, and during dobutamine stress. RESULTS: The mean length of the bridging segment was 24.9 mm (QCA; range 8.4-48.0 mm). Acetylcholine infusion caused severe vasospasm in two patients. In these two patients anginal symptoms were related to vasospasm and sequential testing was discontinued. In the remaining ten patients sequential testing was continued. Coronary flow reserve was normal in all patients: 3.3+/-0.6. In six patients reliable quantitative measurements could be performed during dobutamine stress. The mean systolic diameter of the bridging segment was 1.6+/-0.4 at baseline and 1.3+/-0.3 during dobutamine stress (mean of differences 0.38 (95% CI 0.1-0.7)). The difference between the diastolic and systolic diameter in the bridging segment increased from 0.3+/-0.2 mm at baseline to 1.0+/-0.5 mm during dobutamine infusion (mean of differences 0.6 (95% CI 0.3 to 0.9)). CONCLUSION: Sequential testing for bridging is feasible and may disclose endothelial dysfunction or spasm as an underlying mechanism in a minority of patients. Coronary flow reserve was preserved. Dobutamine stress unmasked further lumen reduction and may give further insight into the clinical significance of myocardial bridging in individual patients. (Neth Heart J 2008;16:10-5.).

Restenosis begets restenosis: implications for stent selection.

BACKGROUND: Identifying the risk for restenosis is of critical importance in the stent selection process of patients undergoing percutaneous coronary intervention (PCI). Therefore, we sought to determine if a history of clinical recurrence (CR) after PCI increases the risk of CR after treatment of a de novo lesion in another coronary artery. METHODS: We retrospectively analysed all 12,763 patients who underwent PCI between 1993 and 2004 and selected patients with two or more interventions in two different native vessels. These patients were divided into two groups: patients without CR, and patients with CR after the first PCI. Clinical recurrence was defined as revascular-isation of the target vessel by either PCI or CABG within one year. RESULTS: A total of 1010 patients with two or more interventions in two different native vessels were identified: 727 patients without and 283 patients with CR after the first PCI. Baseline patient characteristics and conventional risk factors were comparable between the two groups. Patients with a history of CR had a higher risk of CR after a second intervention in a second vessel (OR=3.4, 95% CI=2.3 to 4.9). A total of 112 patients also had a third intervention in a third native vessel: 12 patients with two CR, 30 patients with one CR and 70 patients with no CR after the first two interventions. CR rates in these patients were 50, 17 and 3%, respectively (p<0.001). CONCLUSION: Patients with a history of CR have a markedly increased risk of developing CR after a second or third PCI in a different coronary artery. Therefore, in the decision-making process on whether to use a bare metal stent or drug-eluting stent, the history of CR is a simple and powerful aid. (Neth Heart J 2008;16:376-81.).

Cardiac overexpression of human VEGF(165) by recombinant Semliki Forest virus leads to adverse effects in pressure-induced heart failure.

Semliki Forest virus (SFV) is an efficient vector for cardiac gene delivery. The relatively short transgene expression induced by SFV seems appropriate for angiogenic gene therapy. We tested the effects of SFV expressing vascular endothelial growth factor (VEGF) on cardiac angiogenesis and heart failure in the mRen2 transgenic rat.Six-week-old mRen2 rats received SFV-VEGF or control virus (n=7 each) administered intracoronarily. Twelve days after transfection, cardiac capillary density and function were assessed. Capillary density in cardiac regions where SFV expression was highest had decreased by 20% in the SFV-VEGF-treated group. The decrease in capillary density was accompanied by impaired systolic function as illustrated by increased endsystolic volumes and a 34% decrease in cardiac output.We conclude that the time frame of SFV expression is sufficient to induce structural alterations, but that VEGF in mRen2 transgenic rats did not elicit the expected angiogenic effect. Rather, capillary density was decreased and subsequently cardiac function was impaired. This paradoxical finding is possibly related to the pathophysiology associated with this model and warrants caution if one is to pursue VEGF-mediated, angiogenic therapy before proceeding to a clinical setting. (Neth Heart J 2007;15:335-41.).

Discordance between anatomical and functional coronary stenosis severity.

BACKGROUND.: New developments have made 16-slice multidetector computed tomography (MDCT) a promising technique for detecting significant coronary stenoses. At present, there is a paucity of data on the relation between fractional flow reserve (FFR) measurement and MDCT stenosis detection. OBJECTIVE.: The aim of this study was to investigate the relation between the anatomical severity of coronary artery disease detected by MDCT and functional severity measured by fractional flow reserve (FFR). METHODS.: We studied 53 patients (39 men and 14 women, age 62.5+/-8.1 years) with single-vessel disease scheduled for percutaneous coronary intervention (PCI). All patients underwent MDCT scanning one day prior to PCI and FFR was measured before PCI in the target vessel. RESULTS.: MDCT analysis could be performed in 52 of 53 patients (98.1%) and all patients had adequate FFR and quantitative coronary angiography (QCA) measurements. The mean stenosis diameters calculated by MDCT and QCA were 67.0+/-11.6% and 60.8+/-11.6% respectively. No significant relation was found between MDCT and QCA (r=0.22, p=0.12) The mean FFR in all patients was 0.67+/-0.18. A relation of r=-0.46 (p=0.0006) between QCA and FFR was found. In contrast, no relation between MDCT and FFR could be demonstrated (r=-0.09, p=0.50). Furthermore, a high incidence of false-positive and false-negative findings was present in both diagnostic modalities. CONCLUSION.: There is no clear relation between the anatomical and functional severity of coronary artery disease as defined by MDCT and FFR. Therefore, functional assessment of coronary artery disease remains mandatory for clinical decisionmaking. (Neth Heart J 2007;15:5-11.).

Clinical characteristics, cardiac events and coronary angiographic findings in the prospective PREVEND cohort: an observational study.

BACKGROUND: The use of invasive procedures has mostly been studied in retrospective (multi)- national registries. Limited evidence exists on the association between microalbuminuria and coronary artery disease (CAD). METHODS: The incidence of major adverse cardiac events (MACE) and invasive cardiac procedures was registered between 1997 and 2003 in 8139 subjects, without prior documented CAD, in the PREVEND cohort study (the Netherlands), in which the focus is on microalbuminuria and cardiovascular risk. Qualitative coronary angiographic analysis was performed. RESULTS: During 5.5 years of follow-up, a first MACE occurred in 271 (3.3%) and a first coronary angiography (CAG) was performed in 264 (3.2%) subjects. Of these, 216 CAGs were available for qualitative angiographic analysis. Indications for CAG were stable angina in 129, acute coronary syndrome (ACS) in 55 and ST-elevation myocardial infarction (STEMI) in 32 subjects. Obstructive coronary artery disease was present in 61, 53 and 30 subjects, respectively. A revascularisation was performed in 50 (39%), 50 (91%) and 25 (78%) subjects, respectively. Microalbuminuria was associated with a first MACE, after adjustment for established risk factors. Microalbuminuria was present at baseline in 9% of subjects with normal coronary arteries, in 21% of subjects with one- and two-vessel CAD and in 39% of subjects with threevessel or left main CAD at CAG during follow-up (Ptrend=0.005). CONCLUSION: This large cohort study shows that two-thirds of diagnostic CAGs for stable angina were not followed by a revascularisation, in contrast to CAGs for STEMI or ACS. Furthermore, this study shows that microalbuminuria is associated with CAD. (Neth Heart J 2007;15:133-41.).

Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial.

Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF165 (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n=27) treated with placebo versus phVEGF165-treated patients (n=27) the following results were found: 6 amputations versus 3 (p=not significant [NS]); hemodynamic improvement in 1 versus 7 (p=0.05); improvement in skin ulcers, 0 versus 7 (p=0.01); decrease in pain, 2 versus 5 (p=NS); and overall, 3 versus 14 responding patients (p=0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF165-containing plasmid. There were no substantial adverse events.