Transmural ischemia visualized using routine Chest CTA.

Chest computed tomography (CT) is not routinely used for the diagnosis of myocardial infarction. However, there have been some reports of patients undergoing chest CT for other indications in which ultimately MI was diagnosed due to the presence of areas of myocardial hypoperfusion. The authors present the case of a 60-years old male who is referred due to acute chest pain radiating between the scapulae. Thoracic computed tomography angiography to rule out an aortic dissection revealed an occlusion of the left anterior descending coronary artery with an area of relative hypoperfusion. Hence, the present case demonstrates how using routine thoracic computed tomography angiography, transmural ischemia can be visualized in the setting of an acute myocardial infarction. It should make clinicians aware of the fact it may be beneficial to look for myocardial perfusion abnormalities when assessing chest CT's.

Correlation between quantification of myocardial area at risk and ischemic burden at cardiac computed tomography.

Purpose: This study aims to investigate the correlation between myocardial area at risk at coronary computed tomography angiography (CCTA) and the ischemic burden derived from myocardial computed tomography perfusion (CTP) by using the 17-segment model. Methods: Forty-two patients with chest pain complaints who underwent a combined CCTA and CTP protocol were identified. Patients with reversible ischemia at CTP and at least one stenosis of ≥ 50% at CCTA were selected. Myocardial area at risk was calculated using a Voronoi-based segmentation algorithm at CCTA and was defined as the sum of all territories related to a ≥ 50% stenosis as a percentage of the total left ventricular (LV) mass. The latter was calculated using LV contours which were automatically drawn using a machine learning algorithm. Subsequently, the ischemic burden was defined as the number of segments demonstrating relative hypoperfusion as a percentage of the total amount of segments (=17). Finally, correlations were tested between the myocardial area at risk and the ischemic burden using Pearson's correlation coefficient. Results: A total of 77 coronary lesions were assessed. Average myocardial area at risk and ischemic burden for all lesions was 59% and 23%, respectively. Correlations for ≥ 50% and ≥ 70% stenosis based myocardial area at risk compared to ischemic burden were moderate (r = 0.564; p < 0.01) and good (r = 0.708; p < 0.01), respectively. Conclusion: The relation between myocardial area at risk as calculated by using a Voronoi-based algorithm at CCTA and ischemic burden as assessed by CTP is dependent on stenosis severity.

Ascending aorta curvature and flow displacement are associated with accelerated aortic growth at long-term follow-up: A MRI study in Marfan and thoracic aortic aneurysm patients.

BACKGROUND: Aortic aneurysm formation is associated with increased risk of aortic dissection. Current diagnostic strategies are focused on diameter growth, the predictive value of aortic morphology and function remains underinvestigated. We aimed to assess the long-term prognostic value of ascending aorta (AA) curvature radius, regional pulse wave velocity (PWV) and flow displacement (FD) on aortic dilatation/elongation and evaluated adverse outcomes (proximal aortic surgery, dissection/rupture, death) in Marfan and non-syndromic thoracic aortic aneurysm (NTAA) patients. METHODS: Long-term magnetic resonance imaging (MRI) and clinical follow-up of two previous studies consisting of 21 Marfan and 40 NTAA patients were collected. Baseline regional PWV, AA curvature radius and normalized FD were assessed as well as diameter and length growth rate at follow-up. Multivariate linear regression was performed to evaluate whether baseline predictors were associated with aortic growth.=. RESULTS: Of the 61 patients, 49 patients were included with MRI follow-up (n = 44) and/or adverse aortic events (n = 7). Six had undergone aortic surgery, no dissection/rupture occurred and one patient died during follow-up. During 8.0 [7.3-10.7] years of follow-up, AA growth rate was 0.40 ± 0.31 mm/year. After correction for confounders, AA curvature radius (p = 0.01), but not FD or PWV, was a predictor of AA dilatation. Only FD was associated with AA elongation (p = 0.01). CONCLUSION: In Marfan and non-syndromic thoracic aortic aneurysm patients, ascending aorta curvature radius and flow displacement are associated with accelerated aortic growth at long-term follow-up. These markers may aid in the risk stratification of ascending aorta elongation and aneurysm formation.

Utilizing (serial) coronary computed tomography angiography (CCTA) to predict plaque progression and major adverse cardiac events (MACE): results, merits and challenges.

OBJECTIVES: To present an overview of studies using serial coronary computed tomography angiography (CCTA) as a tool for finding both quantitative (changes) and qualitative plaque characteristics as well as epicardial adipose tissue (EAT) volume changes as predictors of plaque progression and/or major adverse cardiac events (MACE) and outline the challenges and advantages of using a serial non-invasive imaging approach for assessing cardiovascular prognosis. METHODS: A literature search was performed in PubMed, Embase, Web of Science, Cochrane Library and Emcare. All observational cohort studies were assessed for quality using the Newcastle-Ottawa Scale (NOS). The NOS score was then converted into Agency for Healthcare Research and Quality (AHRQ) standards: good, fair and poor. RESULTS: A total of 36 articles were analyzed for this review, 3 of which were meta-analyses and one was a technical paper. Quantitative baseline plaque features seem to be more predictive of MACE and/or plaque progression as compared to qualitative plaque features. CONCLUSIONS: A critical review of the literature focusing on studies utilizing serial CCTA revealed that mainly quantitative baseline plaque features and quantitative plaque changes are predictive of MACE and/or plaque progression contrary to qualitative plaque features. Significant questions regarding the clinical implications of these specific quantitative and qualitative plaque features as well as the challenges of using serial CCTA have yet to be resolved in studies using this imaging technique. KEY POINTS: • Use of (serial) CCTA can identify plaque characteristics and plaque changes as well as changes in EAT volume that are predictive of plaque progression and/or major adverse events (MACE) at follow-up. • Studies utilizing serial CCTA revealed that mainly quantitative baseline plaque features and quantitative plaque changes are predictive of MACE and/or plaque progression contrary to qualitative plaque features. • Ultimately, serial CCTA is a promising technique for the evaluation of cardiovascular prognosis, yet technical details remain to be refined.

Quantification of myocardial ischemia and subtended myocardial mass at adenosine stress cardiac computed tomography: a feasibility study.

Combination of coronary computed tomography angiography (CCTA) and adenosine stress CT myocardial perfusion (CTP) allows for coronary artery lesion assessment as well as myocardial ischemia. However, myocardial ischemia on CTP is nowadays assessed semi-quantitatively by visual analysis. The aim of this study was to fully quantify myocardial ischemia and the subtended myocardial mass on CTP. We included 33 patients referred for a combined CCTA and adenosine stress CTP protocol, with good or excellent imaging quality on CTP. The coronary artery tree was automatically extracted from the CCTA and the relevant coronary artery lesions with a significant stenosis (≥ 50%) were manually defined using dedicated software. Secondly, epicardial and endocardial contours along with CT perfusion deficits were semi-automatically defined in short-axis reformatted images using MASS software. A Voronoi-based segmentation algorithm was used to quantify the subtended myocardial mass, distal from each relevant coronary artery lesion. Perfusion defect and subtended myocardial mass were spatially registered to the CTA. Finally, the subtended myocardial mass per lesion, total subtended myocardial mass and perfusion defect mass (per lesion) were measured. Voronoi-based segmentation was successful in all cases. We assessed a total of 64 relevant coronary artery lesions. Average values for left ventricular mass, total subtended mass and perfusion defect mass were 118, 69 and 7 g respectively. In 19/33 patients (58%) the total perfusion defect mass could be distributed over the relevant coronary artery lesion(s). Quantification of myocardial ischemia and subtended myocardial mass seem feasible at adenosine stress CTP and allows to quantitatively correlate coronary artery lesions to corresponding areas of myocardial hypoperfusion at CCTA and adenosine stress CTP.

Accuracy and reproducibility of fast fractional flow reserve computation from invasive coronary angiography.

Fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) is associated with favourable outcome compared with revascularization based on angiographic stenosis severity alone. The feasibility of the new image-based quantitative flow ratio (QFR) assessed from 3D quantitative coronary angiography (QCA) and thrombolysis in myocardial infarction (TIMI) frame count using three different flow models has been reported recently. The aim of the current study was to assess the accuracy, and in particular, the reproducibility of these three QFR techniques when compared with invasive FFR. QFR was derived (1) from adenosine induced hyperaemic coronary angiography images (adenosine-flow QFR [aQFR]), (2) from non-hyperemic images (contrast-flow QFR [cQFR]) and (3) using a fixed empiric hyperaemic flow [fixed-flow QFR (fQFR)]. The three QFR values were calculated in 17 patients who prospectively underwent invasive FFR measurement in 20 vessels. Two independent observers performed the QFR analyses. Mean difference, standard deviation and 95% limits of agreement (LOA) between invasive FFR and aQFR, cQFR and fQFR for observer 1 were: 0.01 ± 0.04 (95% LOA: -0.07; 0.10), 0.01 ± 0.05 (95% LOA: -0.08; 0.10), 0.01 ± 0.04 (95% LOA: -0.06; 0.08) and for observer 2: 0.00 ± 0.03 (95% LOA: -0.06; 0.07), -0.01 ± 0.03 (95% LOA: -0.07; 0.05), 0.00 ± 0.03 (95% LOA: -0.06; 0.05). Values between the 2 observers were (to assess reproducibility) for aQFR: 0.01 ± 0.04 (95% LOA: -0.07; 0.09), for cQFR: 0.02 ± 0.04 (95% LOA: -0.06; 0.09) and for fQFR: 0.01 ± 0.05 (95% LOA: -0.07; 0.10). In a small number of patients we showed good accuracy of three QFR techniques (aQFR, cQFR and fQFR) to predict invasive FFR. Furthermore, good inter-observer agreement of the QFR values was observed between two independent observers.

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations.

BACKGROUND: Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation. METHODS: In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up. RESULTS: Changes in biventricular dimensions were assessed in 163 Marfan patients (48 % female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. -8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. -18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. -8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. -7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28). CONCLUSION: Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.

Cryosurgery as Additional Treatment in Tenosynovial Giant Cell Tumors.

Introduction. Tenosynovial giant cell tumors (TGCT) emerge from the synovium and can behave aggressively. Surgical resection is the standard treatment. However, up to half of the patients with diffuse type show recurrences. Several additional treatments have been applied to reduce recurrences; none of these treatments was proven to be superior to surgical resection solely. This article describes the results of additional cryosurgery to surgical resection. Materials and Methods. We retrospectively evaluated 141 TGCT patients, between 1999 and 2007. Twelve patients had additional cryosurgery. The knee (n = 8), hip (n = 2), ankle (n = 1), and elbow (n = 1) were affected. Primary outcome variables were treatment indications, recurrences, and complications. Results. Indications for additional cryosurgery were extended disease, bone involvement, and locations that are difficult to surgically get disease-free such as cruciate ligaments. Five patients had recurrent disease, all of which had prior treatments. None of the primary treated patients had recurrent disease. One patient had a deep infection. Discussion. Cryosurgery may serve as an additional treatment for diffuse TCGT in selected cases. However, because of the small number of patients and the heterogeneous group we could not prove an advantage of additional cryosurgery over surgical resection only. Cryosurgery should be considered for further evaluation in a prospective study. If there is any effect it would be helpful, especially in patients with multiple TGCT recurrences.

Coupling between MRI-assessed regional aortic pulse wave velocity and diameters in patients with thoracic aortic aneurysm: a feasibility study.

AIMS: Thoracic aortic aneurysm (TAA) is potentially life-threatening and requires close follow-up to prevent aortic dissection. Aortic stiffness and size are considered to be coupled. Regional aortic stiffness in patients with TAA is unknown. We aimed to evaluate coupling between regional pulse wave velocity (PWV), a marker of vascular stiffness, and aortic diameter in TAA patients. METHODS: In 40 TAA patients (59 ± 13 years, 28 male), regional aortic diameters and regional PWV were assessed by 1.5 T MRI. The incidence of increased diameter and PWV were determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta; S4, suprarenal and S5, infrarenal abdominal aorta). In addition, coupling between regional PWV testing and aortic dilatation was evaluated and specificity and sensitivity were assessed. RESULTS: Aortic diameter was 44 ± 5 mm for the aortic root and 39 ± 5 mm for the ascending aorta. PWV was increased in 36 (19 %) aortic segments. Aortic diameter was increased in 28 (14 %) segments. Specificity of regional PWV testing for the prediction of increased regional diameter was ≥ 84 % in the descending thoracic to abdominal aorta and ≥ 68 % in the ascending aorta and aortic arch. CONCLUSION: Normal regional PWV is related to absence of increased diameter, with high specificity in the descending thoracic to abdominal aorta and moderate results in the ascending aorta and aortic arch.

Screening for coronary artery disease after mediastinal irradiation in Hodgkin lymphoma survivors: phase II study of indication and acceptance†.

BACKGROUND: Cardiovascular diseases are the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. We investigated the role of computed tomographic coronary angiography (CTA) as a screening tool for coronary artery disease (CAD) in asymptomatic HL survivors, and related CTA findings to exercise testing and subsequent interventions. PATIENTS AND METHODS: Patients were eligible for this phase II study if at least 10 years disease-free and treated with mediastinal radiotherapy. Screening consisted of electrocardiogram, exercise testing and CTA. Primary end point was significant CAD (stenosis >50%) on CTA. CTA screening was considered to be indicated for testing in a larger population if ≥6 of 50 CTA scanned patients (12%) would need revascularization. Screening was evaluated with a questionnaire before and after screening. RESULTS: Fifty-two patients were included, and 48 patients underwent CTA. Median age was 47 years, time since HL diagnosis 21 years. There were 45 evaluable scans. Significant CAD on CTA was found in 20% (N = 9), significantly increased compared with the 7% expected abnormalities (P = 0.01, 95% confidence interval 8.3% to 31.7%). In 11% (N = 5), significant stenosis was confirmed at coronary angiography, and revascularization was carried out. Additionally, two patients were treated with optimal medical therapy. Ninety percent of patients were content with screening, regardless whether the CTA showed abnormalities. CONCLUSIONS: Prevalence of significant CAD among HL survivors is high, while asymptomatic even in the presence of life-threatening CAD. This might justify screening by CTA in asymptomatic HL survivors who had mediastinal radiotherapy, but needs to be evaluated in a larger cohort. The trial protocol was approved by the Ethics Committee of the LUMC and registered with ClinicalTrials.gov, NCT01271127.

An unanticipated copy number variant of chromosome 15 disrupting SMAD3 reveals a three-generation family at serious risk for aortic dissection.

Several genes involved in the familial appearance of thoracic aortic aneurysms and dissections (FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new syndromic form of aortic aneurysms and dissections associated with skeletal abnormalities. We discovered a small interstitial deletion of chromosome 15, leading to disruption of SMAD3, in a boy with mild mental retardation, behavioral problems and revealed features of the aneurysms-osteoarthritis syndrome (AOS). Several family members carried the same deletion and showed features including aortic aneurysms and a dissection. This finding demonstrates that haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections, and the skeletal abnormalities that form part of the aneurysms-osteoarthritis syndrome. Interestingly, the identification of this familial deletion is an example of an unanticipated result of a genomic microarray and led to the discovery of important but unrelated serious aortic disease in the proband and family members.

Right ventricular ejection fraction measured by multigated planar equilibrium radionuclide ventriculography is an independent prognostic factor in patients with ischemic heart disease.

BACKGROUND: The number of studies on the prognostic value of the right ventricular ejection fraction (RVEF) in patients with ischemic heart disease (IHD) is limited, whereas it is widely accepted that the left ventricular ejection fraction (LVEF) is a strong prognostic factor. We assessed whether RVEF measured by multigated planar equilibrium radionuclide ventriculography (RNV) is an independent prognostic factor in patients with IHD. METHODS AND RESULTS: We retrospectively identified 347 consecutive patients with IHD (mean age 71 ± 11 years; 18% women) who underwent multigated planar equilibrium RNV between 2004 and 2008 to determine the LVEF, which also provided the RVEF (mean 44.7% ± 11.0%). We categorized patients according to RVEF in ≥40% (n = 240) and <40% (n = 107). Patients were followed for a median of 826 days (range 3-2,400) for the occurrence of events [all-cause mortality (n = 60), cardiac mortality (n = 33), and cardiac hospitalization (n = 78)]. Cox regression analysis with significant univariate predictors [coronary artery revascularization (P = .003), diuretics (P = .03), and statins (P < .001)] showed that an RVEF <40% was associated with a 2.90 (1.68-5.00)-fold higher risk of all-cause death. Accordingly, a decreased RVEF was associated with a 2.15 (1.34-3.43)-fold increase in the risk of cardiac hospitalization and a 5.11(2.32-11.23)-fold risk of cardiac death. CONCLUSION: RVEF measured by multigated planar equilibrium RNV is an independent prognostic factor in patients with chronic IHD.

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome.

Marfan syndrome (MFS) is a connective tissue disorder with major features in cardiovascular, ocular and skeletal systems. Recently, diagnostic criteria were revised where more weight was given to the aortic root dilatation. We applied the revised Marfan nosology in an established adult Marfan population to define practical repercussions of novel criteria for clinical practice and individual patients. Out of 180 MFS patients, in 91% (n = 164) the diagnosis of MFS remained. Out of 16 patients with rejected diagnosis, four patients were diagnosed as MASS (myopia, mitral valve prolapse, borderline non-progressive aortic root dilatation, skeletal findings and striae) phenotype, three as ectopia lentis syndrome and in nine patients no alternative diagnosis was established. In 13 patients, the diagnosis was rejected because the Z-score of the aortic root was <2, although the aortic diameter was larger than 40 mm in six of them. In three other patients, the diagnosis of MFS was rejected because dural ectasia was given less weight in the revised nosology. Following the revised Marfan nosology, the diagnosis of MFS was rejected in 9% of patients, mostly because of the absence of aortic root dilatation defined as Z-score ≥2. Currently used Z-scores seem to underestimate aortic root dilatation, especially in patients with large body surface area (BSA). We recommend re-evaluation of criteria for aortic root involvement in adult patients with a suspected diagnosis of MFS.