Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting.

Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%-50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.

Nondestructive Evaluation of Mechanical and Histological Properties of the Human Aorta With Near-Infrared Spectroscopy.

INTRODUCTION: Ascending aortic dilatation is a well-known risk factor for aortic rupture. Indications for aortic replacement in its dilatation concomitant to other open-heart surgery exist; however, cut-off values based solely on aortic diameter may fail to identify patients with weakened aortic tissue. We introduce near-infrared spectroscopy (NIRS) as a diagnostic tool to nondestructively evaluate the structural and compositional properties of the human ascending aorta during open-heart surgeries. During open-heart surgery, NIRS could provide information regarding tissue viability in situ and thus contribute to the decision of optimal surgical repair. MATERIALS AND METHODS: Samples were collected from patients with ascending aortic aneurysm (n = 23) undergoing elective aortic reconstruction surgery and from healthy subjects (n = 4). The samples were subjected to spectroscopic measurements, biomechanical testing, and histological analysis. The relationship between the near-infrared spectra and biomechanical and histological properties was investigated by adapting partial least squares regression. RESULTS: Moderate prediction performance was achieved with biomechanical properties (r = 0.681, normalized root-mean-square error of cross-validation = 17.9%) and histological properties (r = 0.602, normalized root-mean-square error of cross-validation = 22.2%). Especially the performance with parameters describing the aorta's ultimate strength, for example, failure strain (r = 0.658), and elasticity (phase difference, r = 0.875) were promising and could, therefore, provide quantitative information on the rupture sensitivity of the aorta. For the estimation of histological properties, the results with α-smooth muscle actin (r = 0.581), elastin density (r = 0.973), mucoid extracellular matrix accumulation(r = 0.708), and media thickness (r = 0.866) were promising. CONCLUSIONS: NIRS could be a potential technique for in situ evaluation of biomechanical and histological properties of human aorta and therefore useful in patient-specific treatment planning.

Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms.

Smooth muscle cells and endothelial cells have a remarkable level of plasticity in vascular pathologies. In thoracic and abdominal aortic aneurysms, smooth muscle cells have been suggested to undergo phenotypic switching and to contribute to degradation of the aortic wall structure in response to, for example, inflammatory mediators, dysregulation of growth factor signaling or oxidative stress. Recently, endothelial-to-mesenchymal transition, and a clonal expansion of degradative smooth muscle cells and immune cells, as well as mesenchymal stem-like cells have been suggested to contribute to the progression of aortic aneurysms. What are the factors driving the aortic cell phenotype changes and how vascular flow, known to affect aortic wall structure and to be altered in aortic aneurysms, could affect aortic cell remodeling? In this review, we summarize the current literature on aortic cell heterogeneity and phenotypic switching in relation to changes in vascular flow and aortic wall structure in aortic aneurysms in clinical samples with special focus on smooth muscle and endothelial cells. The differences between thoracic and abdominal aortic aneurysms are discussed.

Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position.

BACKGROUND: The heart's position determined as the heart-aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. PURPOSE: To investigate whether VAT and aortic length influence the HAA. MATERIAL AND METHODS: We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. RESULTS: A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°-130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°-124.7°) in patients with excessive VAT (P < 0.001). CONCLUSION: An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease.

AIMS: The aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). METHODS: Medical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. RESULTS: Prevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. CONCLUSIONS: Almost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony.

Susceptibility to Cardiac Arrhythmias and Sympathetic Nerve Growth in VEGF-B Overexpressing Myocardium.

VEGF-B gene therapy is a promising proangiogenic treatment for ischemic heart disease, but, unexpectedly, we found that high doses of VEGF-B promote ventricular arrhythmias (VAs). VEGF-B knockout, alpha myosin heavy-chain promoter (αMHC)-VEGF-B transgenic mice, and pigs transduced intramyocardially with adenoviral (Ad)VEGF- B186 were studied. Immunostaining showed a 2-fold increase in the number of nerves per field (76 vs. 39 in controls, p < 0.001) and an abnormal nerve distribution in the hypertrophic hearts of 11- to 20-month-old αMHC-VEGF-B mice. AdVEGF-B186 gene transfer (GT) led to local sprouting of nerve endings in pig myocardium (141 vs. 78 nerves per field in controls, p < 0.05). During dobutamine stress, 60% of the αMHC-VEGF-B hypertrophic mice had arrhythmias as compared to 7% in controls, and 20% of the AdVEGF-B186-transduced pigs and 100% of the combination of AdVEGF-B186- and AdsVEGFR-1-transduced pigs displayed VAs and even ventricular fibrillation. AdVEGF-B186 GT significantly increased the risk of sudden cardiac death in pigs when compared to any other GT with different VEGFs (hazard ratio, 500.5; 95% confidence interval [CI] 46.4-5,396.7; p < 0.0001). In gene expression analysis, VEGF-B induced the upregulation of Nr4a2, ATF6, and MANF in cardiomyocytes, molecules previously linked to nerve growth and differentiation. Thus, high AdVEGF-B186 overexpression induced nerve growth in the adult heart via a VEGFR-1 signaling-independent mechanism, leading to an increased risk of VA and sudden cardiac death.

A smaller heart-aorta-angle associates with ascending aortic dilatation and increases wall shear stress.

OBJECTIVES: The aim of this study was to evaluate whether the orientation of the heart, measured as an angle between the long axis of the heart and ascending aorta midline (heart-aorta-angle, HAA), associates with ascending aortic (AA) dilatation. Furthermore, the association between HAA and wall shear stress (WSS) was studied. METHODS: HAA was retrospectively measured in 1000 consecutive coronary artery computed tomographic angiography (CCTA) images in patients with low-to-moderate pretest probability for coronary artery disease (CAD). To evaluate the effects of HAA on AA flow, 4D flow MRI was performed for 28 patients with AA dilatation (> 40 mm) and WSS was analyzed. RESULTS: The mean age of patients undergoing CCTA was 52.9 ± 9.8 years; 66.5% were women. Their median HAA was 128.7° and interquartile range 123.3-134.1°. HAA was significantly smaller in patients with dilated AA (median 126.7° [121.3-130.8°]) compared with the patients with normal AA (median 129.5° [124.3-135.3°], p < 0.001). HAA was smaller in males (p < 0.001) and in patients with diabetes (p = 0.016), hypertension (p = 0.001), CAD (p = 0.003), hypercholesterolemia (p < 0.001), and bicuspid aortic valve (p = 0.025) than without these factors. In a subpopulation without any of these underlying diseases (n = 233), HAA was still significantly smaller in the patients with dilated AA (median 127.9° [124.3-134.3°]) compared with patients with normal AA (median 131.9° [127.6-136.9°], p = 0.013). In 4D flow MRI, a smaller HAA correlated with increased total WSS in the outer curvature of the proximal AA (r = - 0.510, p = 0.006). CONCLUSION: A smaller HAA associates with AA dilatation and affects the blood flow in the proximal AA. KEY POINTS: • A smaller angle between the long axis of the heart and ascending aorta midline associated with ascending aortic dilatation. • A smaller heart-aorta-angle correlated with increased total wall shear stress in the outer curvature of the proximal ascending aorta.

High prevalence of ascending aortic dilatation in a consecutive coronary CT angiography patient population.

OBJECTIVES: To clarify the prevalence and risk factors of ascending aortic (AA) dilatation according to ESC 2014 guidelines. METHODS: This study included 1000 consecutive patients scheduled for diagnostic coronary artery computed tomographic angiography. AA diameter was retrospectively measured in 3 planes: sinus valsalva, sinotubular junction, and tubular part. The threshold for AA dilatation was set to > 40 mm which has been suggested as an upper normal limit for AA diameter in ESC 2014 guidelines on aortic diseases. Aortic size index (ASI) using the ratio between aortic diameter and body surface area (BSA) was applied as a comparative measurement. The threshold for AA dilatation was set to the upper limit of normal distribution exceeding two standard deviations (95%). Risk factors for AA dilatation were collected from medical records. RESULTS: The patients' mean age was 52.9 ± 9.8 years (66.5% women). The prevalence of AA dilatation was 23.0% in the overall study population (52.5% males) and 15.1% in the subgroup of patients with no coronary artery disease or bicuspid (BAV)/mechanical aortic valve (n = 365). According to the normal-distributed ASI values, the threshold for sinus valsalva was defined as 23.2 mm/m2 and for tubular part 22.2 mm/m2 in the subgroup. Higher BSA was associated with larger AA dimensions (r = 0.407, p < 0.001). Male gender (p < 0.001), BAV (p < 0.001), hypertension (p = 0.009) in males, and smoking (p < 0.001) appeared as risk factors for AA dilatation. CONCLUSIONS: The prevalence of AA dilatation is high with current ESC guidelines for normal AA dimension, especially in males. Body size is strongly associated with AA dimensions; it would be more reliable to use BSA-adjusted AA diameters for the definition of AA dilatation. KEY POINTS: • The prevalence of AA dilatation is high in patients who are candidates for coronary CT angiography. • Body size is strongly associated with AA dimensions.

Electrical and mechanical dyssynchrony in patients with right bundle branch block.

BACKGROUND: Though fairly benign reputation, the right bundle branch block (RBBB) can cause left ventricular mechanical dyssynchrony (LVMD). Still, the relationship between electrical disturbance and LVMD is partly unclear among these patients. METHODS: Thirty patients with RBBB and 60 matching controls were studied with vector electrocardiography and myocardial perfusion imaging phase analysis. RBBB group was divided into those with and those without LVMD. RESULTS: Prevalence of LVMD among RBBB patients was 50% and among controls 22%. Odds ratio (OR) for LVMD in patients with RBBB vs controls without RBBB was 3.6 (95% CI 1.4 to 9.3). Ejection fraction (EF), end-systolic volume, the angle between QRS and T vectors, and the QRS angle in the sagittal plane were significantly different between RBBB patients with and without LVMD. The QRS duration was comparable in these groups. EF associated independently with LVMD, explaining 60% of its variation. A cut-off value of EF ≤ 55% detected LVMD in 100% specificity (sensitivity of 47%). CONCLUSION: Half of the patients with RBBB had LVMD. The OR for LVMD between RBBB and normal ECG was 3.6. It seems that EF, rather than electrical parameters, is the main determinant of LVMD. This information might be useful when evaluating indications for cardiac resynchronization therapy.

Aortic dilatation associates with flow displacement and increased circumferential wall shear stress in patients without aortic stenosis: A prospective clinical study.

BACKGROUND: The relationship between blood flow characteristics and ascending aortic (AA) dilatation has not been studied in patients with a tricuspid aortic valve (TAV) without aortic stenosis. PURPOSE: To evaluate whether 4D flow characteristics determined in MRI are related to AA dilatation by comparing dilated AA and nondilated AA subjects with TAV. STUDY TYPE: Prospective. POPULATION: Twenty patients with dilated AA and 20 age-matched patients with nondilated AA. FIELD STRENGTH/SEQUENCE: 1.5T/4D flow, 2D flow, and anatomic images. ASSESSMENT: Altogether, 16 different 4D flow parameters were assessed in 10 planes in the thoracic aorta. Intra- and interobserver reproducibility were analyzed. STATISTICAL TESTS: Independent t-test for normally distributed and the Mann-Whitney test for skewed distributed parameters were used. A paired-samples t-test was used to compare 2D and 4D flow parameters. Intraclass correlation coefficient (ICC) was used in intra- and interobserver reproducibility analysis. RESULTS: Aortic flow was displaced from the centerline of the aorta in the proximal and tubular planes. Flow displacement (FD) was greatest in the proximal plane of AA and was higher in dilated AA (4.5%, range 3.0-5.8%) than in nondilated AA (2.0%, 1.0-3.0%, P < 0.001). Total wall shear stress (WSS) values were 1.3 ± 0.4 times higher on the displaced side than on the opposite side of the aorta (P < 0.01). The circumferential WSS (WSSC ) ratio to total WSS was greater in dilated AA, being 0.48 ± 0.11 vs. 0.32 ± 0.09 in the inner curvature of the proximal AA (P < 0.001) and 0.37 ± 0.11 vs. 0.26 ± 0.07 in the whole aortic ring in the distal AA (P < 0.001). Depending on 4D flow parameters, reproducibility varied from excellent (ICC = 0.923) to very low (ICC = 0.204). DATA CONCLUSION: The present study demonstrates that 4D flow measurements help to visualize the pathological flow patterns related to aortic dilatation. Flow displacement and an increased WSSc/WSS ratio are significantly associated with AA dilatation. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:136-145.

Relationships between electrical and mechanical dyssynchrony in patients with left bundle branch block and healthy controls.

BACKGROUND: Abnormal electrical activation may cause dyssynchronous left ventricular (LV) contraction. In this study, we characterized and analyzed electrical and mechanical dyssynchrony in patient with left bundle branch block (LBBB) and healthy controls. METHODS: Myocardial perfusion imaging (MPI) data from 994 patients were analyzed. Forty-three patient fulfilled criteria for LBBB and 24 for controls. Electrical activation was characterized with vector electrocardiography (VECG) and LV function including mechanical dyssynchrony with ECG-gated MPI phase analysis. RESULTS: QRS duration (QRSd; r = 0.69, P < .001) and a few other VECG parameters correlated significantly with phase bandwidth (phaseBW) representing mechanical dyssynchrony. End-diastolic volume (EDV; r = 0.59, P < .001), ejection fraction and end-systolic volume correlated also with phaseBW. QRSd (ß = 0.47, P < .001) and EDV (ß = 0.36, P = .001) were independently associated with phaseBW explaining 55% of its variation. Sixty percent of patients with LBBB had significant mechanical dyssynchrony. Those patients had wider QRSd (159 vs 147 ms, P = .013) and larger EDV (144 vs 94 mL, P = .008) than those with synchronous LV contraction. Cut-off values for mechanical dyssynchrony seen in patients with LBBB were QRSd ≥ 165 ms and EDV ≥ 109 mL. CONCLUSIONS: Despite obvious conduction abnormality, LBBB is not always accompanied by mechanical dyssynchrony. QRSd and EDV explained 55% of variation seen in phaseBW. These two parameters were statistically different between LBBB cases with and without mechanical dyssynchrony.

Serum Neurofilament Light Chain Concentration Correlates with Infarct Volume but Not Prognosis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: We studied serum neurofilaments diagnostic value in patients with acute ischemic stroke (AIS) or TIA and evaluated any correlation with symptom severity, cerebral infarction volume, aetiology, and clinical outcome. METHODS: One hundred and thirty-six patients (101 with AIS, and 35 with TIA) were included. Acute-phase serum neurofilament light chain (sNfL) was analyzed with a novel ultrasensitive single molecule array (Simoa). Cerebral infarction volume was measured from brain computed tomography in the subacute phase (>2 days). Stroke aetiology was defined by trial of ORG 10172 in acute stroke treatment classification, severity by National Institute of Health stroke scale (NIHSS) and the degree of disability by the Modified Rankin Scale (mRS) after 90 days. RESULTS: sNfL was markedly higher in patients with AIS (89.5 pg/mL [IQR: 44.7-195.3]) than with TIA (25.2 pg/mL [IQR: 14.6-48.0]), P= <.001), also after adjusting for age, NIHSS, and stroke volume (P= .003). In receiver operating characteristic analysis, sNfL concentration greater than or equal to 49 pg/mL proved to be the best cut-off value to differentiate between patients with stroke and those with TIA (sensitivity of 73% and specificity of 80%). sNfL concentration significantly correlated with cerebral infarction volume (r = .413, P= <.001), this association remained significant after adjusting for established predictors (P= .019). Patients with AIS due to cardioembolism or large artery atherosclerosis had the highest sNfL concentrations. NIHSS on admission (r = .343, P = <.001) and mRS scores after 3 months (r = .306, P = .004) correlated with sNfL concentration, however functional outcome 3 months after stroke was not associated with sNfL after adjusting for potential confounders. CONCLUSIONS: Cases with stroke were distinguishable from those with TIA following the determination of sNfL in the blood samples. The presence and amount of axonal damage estimated by sNfL correlated with the final cerebral infarction volume but was not predictive of degree of disability.

Respiratory motion reduction with a dual gating approach in myocardial perfusion SPECT: Effect on left ventricular functional parameters.

BACKGROUND: Respiratory motion (RM) complicates the analysis of myocardial perfusion (MP) single-photon emission computed tomography (SPECT) images. The effects of RM on left ventricular (LV) functional variables have not been thoroughly investigated. METHODS AND RESULTS: Thoracic electrical bioimpedance and electrocardiographic signals were recorded from eighteen patients undergoing the rest phase of a 1-day stress/rest cardiac-gated MP-SPECT examination. The signals and list-mode emission data were retrospectively processed to yield standard cardiac- and dual-gated (respiratory and cardiac gating) image sets applying a novel algorithm. LV volume, MP, shape index (SI), wall motion (WM), wall thickening (WT), and phase analysis parameters were measured with Quantitative Perfusion SPECT/Quantitative Gated SPECT software (Cedars-Sinai Medical Center). Image quality was evaluated by three experienced physicians. Dual gating increased LV volume (77.1 ± 26.8 vs 79.8 ± 27.6 mL, P = .006) and decreased SI (0.57 ± 0.05 vs 0.56 ± 0.05, P = .036) and global WT (39.0 ± 11.8% vs 36.9 ± 9.4%, P = .034) compared to cardiac gating, but did not significantly alter perfusion, WM or phase analysis parameters or image quality (P > .05). CONCLUSIONS: RM reduction has an effect on LV volume, shape, and WT parameters. RM exerts no significant effect on phase analysis parameters.

Adenoviral intramyocardial VEGF-DΔNΔC gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up.

AIMS: We evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-DΔNΔC gene therapy in patients with refractory angina. METHODS AND RESULTS: Thirty patients were randomized to AdVEGF-DΔNΔC (AdVEGF-D) or placebo (control) groups. Electromechanical NOGA mapping and radiowater PET were used to identify hibernating viable myocardium where treatment was targeted. Safety, severity of symptoms, quality of life, lipoprotein(a) [Lp(a)] and routine clinical chemistry were measured. Myocardial perfusion reserve (MPR) was assessed with radiowater PET at baseline and after 3- and 12-months follow-up. Treatment was well tolerated. Myocardial perfusion reserve increased significantly in the treated area in the AdVEGF-D group compared with baseline (1.00 ± 0.36) at 3 months (1.31 ± 0.46, P = 0.045) and 12 months (1.44 ± 0.48, P = 0.009) whereas MPR in the reference area tended to decrease (2.05 ± 0.69, 1.76 ± 0.62, and 1.87 ± 0.69; baseline, 3 and 12 months, respectively, P = 0.551). Myocardial perfusion reserve in the control group showed no significant change from baseline to 3 and 12 months (1.26 ± 0.37, 1.57 ± 0.55, and 1.48 ± 0.48; respectively, P = 0.690). No major changes were found in clinical chemistry but anti-adenovirus antibodies increased in 54% of the treated patients compared with baseline. AdVEGF-D patients in the highest Lp(a) tertile at baseline showed the best response to therapy (MPR 0.94 ± 0.32 and 1.76 ± 0.41 baseline and 12 months, respectively, P = 0.023). CONCLUSION: AdVEGF-DΔNΔC gene therapy was safe, feasible, and well tolerated. Myocardial perfusion increased at 1 year in the treated areas with impaired MPR at baseline. Plasma Lp(a) may be a potential biomarker to identify patients that may have the greatest benefit with this therapy.

Pericardial fluid: assessment and examination.

Pericardial fluid is a common finding on echocardiography. Less than 10 mm of fluid on ultrasound scan is not necessarily associated with any significant illness. Clinical examination, blood count, renal and liver enzymes and thyroid function tests as well as inflammatory marker tests are often adequate for a patient who is in good health. A significant amount of fluid requires further investigations, especially in a symptomatic patient. Cancers, infections and various systemic diseases are the most common causes of prominent effusion.

Etiology, diagnostics and treatment of cardiogenic stroke.

Approximately 15 to 40% of cerebral infarctions and transient ischemic attacks (TIA) are of cardiac origin. Knowledge of a significant cardiac disease arouses the suspicion of cardiogenic embolism, but its diagnosis requires identification of the source of embolism. Atrial fibrillation is the most common cause of cardiogenic embolism, and should be actively sought after an ischemic cerebrovascular attact. The detection of atrial fibrillation or an intracardiac thrombus in these patients requires initiation of permanent anticoagulant therapy. Transesophageal echocardiography (TEE) has proven to be more sensitive than transthoracic echocardiography (TTE) in detecting certain possible cardiogenic sources of embolism.

Effect of middle cerebral artery territory ischemic stroke on QT interval.

BACKGROUND: Prolonged QT interval associates with increased risk for sudden cardiac death after acute ischemic stroke. However, pathophysiology of prolonged QT interval after stroke is poorly elucidated. In this study, we investigated whether QT interval dynamics is different in patients with right and left middle cerebral artery (MCA) territory stroke. METHOD: Electrocardiogram (ECG) intervals were compared between baseline (retrieved retrospectively from medical records) and admission (acquired at the acute hospital admission) in 33 patients (65 ± 9.5 years) with right or left MCA territory ischemic stroke. Head computed tomography (CT), cardiac ultrasound, and cardiac CT scans were undertaken. RESULTS: Stroke was located in the right MCA territory in 21 (64%) and in the left MCA territory in 12 (36%) patients. Patients with right and left MCA stroke were similar with respect to time interval between baseline and admission ECG recordings, positive history of heart disease, and left ventricular dimensions. Increase in heart rate-corrected QT interval (QTc) from baseline to admission was demonstrated to occur more often in patients with right (16 of 21; 76%) than in patients with left (3 of 12; 25%; P < .01) MCA stroke. ΔQTc between baseline and admission was significantly longer in patients with right (23 ± 23 milliseconds) than in patients with left (-11 ± 19 milliseconds; P < .0001) MCA stroke. Percent ΔQTc between baseline and admission was longer in patients with right (5.5% ± 5.5%) than in patients with left (-2.6% ± 4.7%; P < .001) MCA stroke. CONCLUSIONS: Right MCA ischemic stroke results in prolongation of QT interval. Findings indicate cerebral asymmetry in brain-heart interaction during acute ischemic stroke.

Central Obesity is Associated with Increased Left Ventricular Maximal Wall Thickness and Intrathoracic Adipose Tissue Measured with Cardiac Magnetic Resonance.

INTRODUCTION: Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. AIM: We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. METHODS: LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) <30 kg/m2) and 18 non-obese male controls. RESULTS: LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm2, p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm2, p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = - 0.403, p = 0.037) and LV stroke volume (SV) (r = - 0.425, p = 0.027). MAT correlated inversely with SV (r = - 0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, ß = 0.617, p < 0.001). The optimal cut-off with Youden's index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). CONCLUSIONS: CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.