Juhani Airaksinen

Cardiac Positron Emission Tomography/Computed Tomography Imaging Accurately Detects Anatomically and Functionally Significant Coronary Artery Disease

Background— Computed tomography (CT) is increasingly used to detect coronary artery disease, but the evaluation of stenoses is often uncertain. Perfusion imaging has an established role in detecting ischemia and guiding therapy. Hybrid positron emission tomography (PET)/CT allows combination angiography and perfusion imaging in short, quantitative, low-radiation-dose protocols. Methods and Results— We enrolled 107 patients with an intermediate (30% to 70%) pretest likelihood of coronary artery disease. All patients underwent PET/CT (quantitative PET with 15O-water and CT angiography), and the results were compared with the gold standard, invasive angiography, including measurement of fractional flow reserve when appropriate. Although PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%. The radiation dose of the combined PET and CT protocols was 9.3 mSv (86 patients) with prospective triggering and 21.8 mSv (21 patients) with spiral CT. Conclusion— Cardiac hybrid PET/CT imaging allows accurate noninvasive detection of coronary artery disease in a symptomatic population. The method is feasible and can be performed routinely with <10 mSv in most patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00627172.

Clinical Value of Absolute Quantification of Myocardial Perfusion With 15O-Water in Coronary Artery Disease

Background— The standard interpretation of perfusion imaging is based on the assessment of relative perfusion distribution. The limitations of that approach have been recognized in patients with multivessel disease and endothelial dysfunction. To date, however, no large clinical studies have investigated the value of measuring quantitative blood flow and compared that with relative uptake. Methods and Results— One hundred four patients with moderate (30%–70%) pretest likelihood of coronary artery disease (CAD) underwent PET imaging during adenosine stress using 15O-water and dynamic imaging. Absolute myocardial blood flow was calculated from which both standard relative myocardial perfusion images and images scaled to a known absolute scale were produced. The patients and the regions then were classified as normal or abnormal and compared against the reference of conventional angiography with fractional flow reserve. In patient-based analysis, the positive predictive value, negative predictive value, and accuracy of absolute perfusion in the detection of any obstructive CAD were 86%, 97%, and 92%, respectively, with absolute quantification. The corresponding values with relative analysis were 61%, 83%, and 73%, respectively. In region-based analysis, the receiver operating characteristic curves confirmed that the absolute quantification was superior to relative assessment. In particular, the specificity and positive predictive value were low using just relative differences in flow. Only 9 of 24 patients with 3-vessel disease were correctly assessed using relative analysis. Conclusions— The measurement of myocardial blood flow in absolute terms has a significant impact on the interpretation of myocardial perfusion. As expected, multivessel disease is more accurately detected. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00627172.

Candidate locus analysis of familial ascending aortic aneurysms and dissections confirms the linkage to the chromosome 5q13-14 in Finnish families.

OBJECTIVEnThe purpose of the study was to carry out a candidate gene analysis in families with familial thoracic aortic aneurysms and dissections.nnnMETHODSnThe study material consisted of 11 Finnish families (with 115 members genotyped) who underwent echocardiographic examination for measurement of the aortic root diameter. Selected candidate genes included the loci for Marfan and Ehlers-Danlos syndromes, the genes of matrix metalloproteinases 3 and 9 and tissue inhibitor of metalloproteinase 2 as well two loci on the chromosomes 5q13-14 and 11q23.2-q24, previously found to be linked to the disease.nnnRESULTSnThe chromosomal locus 5q13-14 was linked to the disease risk (nonparametric linkage score 3.0, P =.005) confirming the previous linkage. Other candidate genes and loci were excluded as major loci in these families.nnnCONCLUSIONSnThe identification of the gene at chromosomal location 5q13-14 causing the development of such diseases would give us important knowledge on the pathogenesis of the disease and enable the identification of subjects at risk. This in turn would lead to appropriate treatment before the occurrence of fatal complications and, likely, to the development of new treatment methods.

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCEnEvidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies.nnnOBJECTIVEnTo determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI).nnnDESIGN, SETTING, AND PARTICIPANTSnA randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized.nnnINTERVENTIONSnPatients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (nu2009=u200955 in the xenon group) or hypothermia treatment alone (nu2009=u200955 in the control group).nnnMAIN OUTCOMES AND MEASURESnThe primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months.nnnRESULTSnAmong the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], Pu2009=u2009.006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; Pu2009=u2009.68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; Pu2009=u2009.053).nnnCONCLUSIONS AND RELEVANCEnAmong comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00879892.

18 F-FDG positron emission tomography/computed tomography in infective endocarditis

BackgroundThe diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in IE.MethodsSixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18F-FDG-PET/CT. 18F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference.ResultsThere was strong, focal 18F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUVmax of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE.Conclusions18F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

Comparison of Results of Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention in Octogenarians

The aim of the present study was to compare the outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients aged ≥80 years. The present analysis included 274 patients who underwent isolated CABG and 393 patients who underwent PCI. The patients undergoing PCI had a greater prevalence of a history of cardiac surgery and recent myocardial infarction and had more frequently undergone emergency revascularization. Patients undergoing CABG had a significantly greater prevalence of 3-vessel coronary artery disease. The unadjusted 30-day mortality rate was 8.8% after CABG and 7.4% after PCI (p = 0.514). However, on multivariate analysis, CABG was associated with a significantly increased risk of 30-day mortality (odds ratio 2.246, 95% confidence interval 1.141 to 4.422). The unadjusted overall intermediate survival was significantly poorer after PCI (at 5 years, CABG 72.2% vs PCI 59.5%, p = 0.004), but this was not confirmed on multivariate analysis. PCI and CABG had similar intermediate survival rates when adjusted for propensity score (p = 0.698), a finding confirmed by the analysis of 130 propensity score-matched pairs (at 5 years, CABG 66.4% vs PCI 58.9%, p = 0.730). In conclusion, the survival of patients aged ≥80 years undergoing CABG is excellent, and the suboptimal survival after PCI seems to be related to the disproportionately greater risk of these patients compared to those undergoing CABG. When adjusted for important clinical variables, PCI and CABG achieved similar intermediate results.

Prediction of severe bleeding after coronary surgery: the WILL-BLEED Risk Score.

Severe perioperative bleeding after coronary artery bypass grafting (CABG) is associated with poor outcome. An additive score for prediction of severe bleeding was derived (n=2494) and validated (n=1250) in patients from the E-CABG registry. Severe bleeding was defined as E-CABG bleeding grades 2-3 (transfusion of >4 units of red blood cells or reoperation for bleeding). The overall incidence of severe bleeding was 6.4u2009%. Preoperative anaemia (3 points), female gender (2 points), eGFR <45 ml/min/1.73 m2 (3 points), potent antiplatelet drugs discontinued less than five days (2 points), critical preoperative state (5 points), acute coronary syndrome (2 points), use of low-molecular-weight heparin/fondaparinux/unfractionated heparin (1 point) were independent predictors of severe bleeding. The WILL-BLEED score was associated with increasing rates of severe bleeding in both the derivation and validation cohorts (scores 0-3: 2.9u2009% vs 3.4u2009%; scores 4-6: 6.8u2009% vs 7.5u2009%; scores>6: 24.6u2009% vs 24.2u2009%, both p<0.0001). The WILL-BLEED score had a better discriminatory ability (AUC 0.725) for prediction of severe bleeding compared to the ACTION (AUC 0.671), CRUSADE (AUC 0.642), Papworth (AUC 0.605), TRUST (AUC 0.660) and TRACK (AUC 0.640) bleeding scores. The net reclassification index and integrated discrimination improvement using the WILL-BLEED score as opposed to the other bleeding scores were significant (p<0.0001). The decision curve analysis demonstrated a net benefit with the WILL-BLEED score compared to the other bleeding scores. In conclusion, the WILL-BLEED risk score is a simple risk stratification method which allows the identification of patients at high risk of severe bleeding after CABG.

Aortic valve insufficiency in patients with chronic rheumatic diseases

Aortic valve lesions are often found in patients with rheumatic diseases, but their clinical significance has not been properly evaluated. In the present study, the echocardiographic files of the cardiology unit of the Oulu University Hospital were screened for a diagnosis of aortic insufficiency (AI). The aetiology of the valve disease and specific details of the rheumatic disease were evaluated in 160 patients. Twenty-eight patients (18%) had a history of rheumatic fever. Rheumatic disease was found in 14 patients (8.8%) with AI, which is significantly more than the prevalence of rheumatic diseases (1.8%) in the corresponding age group (35–100 years) in Finland. Rheumatoid arthritis or juvenile rheumatoid arthritis was found in seven patients (4.4%), whereas ankylosing spondylitis or seronegative spondylarthropathy were found in four patients (2.5%). Other rheumatic diseases included Takayasus arteritis (two patients) and scleroderma (one patient). When 38 patients with pure AI without other possible aetiology were analysed, rheumatic disease was found in five patients (13%). Patients with rheumatic disease as a potential aetiology of AI often had symptomatic valve disease, which required surgical treatment, although great differences between different aetiologies were not found.

Gyrocardiography: A New Non-invasive Monitoring Method for the Assessment of Cardiac Mechanics and the Estimation of Hemodynamic Variables

Gyrocardiography (GCG) is a new non-invasive technique for assessing heart motions by using a sensor of angular motion – gyroscope – attached to the skin of the chest. In this study, we conducted simultaneous recordings of electrocardiography (ECG), GCG, and echocardiography in a group of subjects consisting of nine healthy volunteer men. Annotation of underlying fiducial points in GCG is presented and compared to opening and closing points of heart valves measured by a pulse wave Doppler. Comparison between GCG and synchronized tissue Doppler imaging (TDI) data shows that the GCG signal is also capable of providing temporal information on the systolic and early diastolic peak velocities of the myocardium. Furthermore, time intervals from the ECG Q-wave to the maximum of the integrated GCG (angular displacement) signal and maximal myocardial strain curves obtained by 3D speckle tracking are correlated. We see GCG as a promising mechanical cardiac monitoring tool that enables quantification of beat-by-beat dynamics of systolic time intervals (STI) related to hemodynamic variables and myocardial contractility.

Early vascular healing after titanium-nitride-oxide-coated stent versus platinum-chromium everolimus-eluting stent implantation in patients with acute coronary syndrome.

Data on early vascular healing response of novel stent designs are scarce. In this randomized prospective trial, we sought to compare early neointimal coverage of cobalt–chromium-based titanium–nitride–oxide-coated bioactive stents (CoCr-BAS) versus platinum–chromium everolimus-eluting stents (PtCr-EES) at 2-month follow-up in patients with acute coronary syndrome (ACS). Forty patients with ACS were randomized to receive either CoCr-BAS (nu2009=u200919) or PtCr-EES (nu2009=u200921). Neointimal strut coverage and strut apposition were examined by optical coherence tomography; and coronary flow reserve (CFR), fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were assessed using a coronary pressure wire at 2 months. Two patients in the PtCr-EES underwent OCT out of the time frame of the study, and were excluded from analysis. At 63u2009±u20098 days, 302 cross-sections (3412 struts) were analysed in the CoCr-BAS group, and 324 cross-sections (3460 struts) in the PtCr-EES group. Median [IQR] neointimal thickness was 203 [108] µm and 42.2 [41] µm for CoCr-BAS and PtCr-EES, respectively (pu2009<u20090.001). Median [IQR] percentage of uncovered struts was 1.2 [2.8] % versus 11.3 [17.7] %, respectively (pu2009<u20090.001). Flow measurements were comparable between the two groups (pu2009>u20090.05 for all). CoCr-BAS showed earlier and more adequate neointimal coverage of struts at 2 months, compared with PtCr-EES, but with more neointimal hyperplasia. Functional healing as assessed by CFR, FFR, and IMR was similar between the two stent arms.