Imagerie cardiaque non invasive: apport spécifique en clinique des nouvelles modalités (II). Evaluation fonctionnelle [Cardiac imaging: specific clinical role of newly developed non invasive techniques. Part II: functional evaluation].

The non-invasive evaluation of myocardial ischemia is a priority in cardiology. The preferred initial non-invasive test is exercise ECG, because of its high accessibility and its low cost. Stress radionuclide myocardial perfusion imaging or stress echocardiography are now routinely performed, and new non-invasive techniques such as perfusion-MRI, dobutamine stress-MRI or 82rubidium perfusion PET have recently gained acceptance in clinical practice. In the same time, an increasing attention has been accorded to the concept of myocardial viability in the decisional processes in case of ischemic heart failure. In this indication, MRI with late enhancement after intravenous injection of gadolinium and 18F-FDG PET showed an excellent diagnostic accuracy. This article will present these new imaging modalities and their accepted indications.

Transient Ischemic Dilation (TID) ratio measurement during Rb-82 cardiac PET: Comparison between three different software packages.

Background: TIDratio indirectly reflects myocardial ischemia and is correlated with cardiacprognosis. We aimed at comparing the influence of three different softwarepackages for the assessment of TID using Rb-82 cardiac PET/CT. Methods: Intotal, data of 30 patients were used based on normal myocardial perfusion(SSS<3 and SRS<3) and stress myocardial blood flow 2mL/min/g)assessed by Rb-82 cardiac PET/CT. After reconstruction using 2D OSEM (2Iterations, 28 subsets), 3-D filtering (Butterworth, order=10, ωc=0.5), data were automatically processed, and then manually processed fordefining identical basal and apical limits on both stress and rest images.TIDratio were determined with Myometrix®, ECToolbox® and QGS®software packages. Comparisons used ANOVA, Student t-tests and Lin concordancetest (ρc). Results: All of the 90 processings were successfullyperformed. TID ratio were not statistically different between software packageswhen data were processed automatically (P=0.2) or manually (P=0.17). There was a slight, butsignificant relative overestimation of TID with automatic processing incomparison to manual processing using ECToolbox® (1.07 ± 0.13 vs 1.0± 0.13, P=0.001)and Myometrix® (1.07 ± 0.15 vs 1.01 ± 0.11, P=0.003) but not using QGS®(1.02 ±0.12 vs 1.05 ± 0.11, P=0.16). The best concordance was achieved between ECToolbox®and Myometrix® manual (ρc=0.67) processing.Conclusion: Using automatic or manual mode TID estimation was not significantlyinfluenced by software type. Using Myometrix® or ECToolbox®TID was significantly different between automatic and manual processing, butnot using QGS®. Software package should be account for when definingTID normal reference limits, as well as when used in multicenter studies. QGS®software seemed to be the most operator-independent software package, whileECToolbox® and Myometrix® produced the closest results.

Pericardial fat volume correlates with coronary vasomotion

Purpose: Recent studies showed that pericardial fat was independently correlated with the development of coronary artery disease (CAD). The mechanism remains unclear. We aimed at assessing a possible relationship between pericardial fat volume and endothelium-dependent coronary vasomotion, a surrogate of future cardiovascular events.Methods: Fifty healthy volunteers without known CAD or cardiovascular risk factors (CRF) were enrolled. They all underwent a dynamic Rb- 82 cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, during MBF response to cold pressure test (CPT-MBF) and adenosine stress. Pericardial fat volume (PFV) was measured using a 3D volumetric CT method and common biological CRF (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hs-CRP). Relationships between MBF response to CPT, PFV and other CRF were assessed using non-parametric Spearman correlation and multivariate regression analysis of variables with significant correlation on univariate analysis (Stata 11.0).Results: All of the 50 participants had normal MBF response to adenosine (2.7±0.6 mL/min/g; 95%CI: 2.6−2.9) and myocardial flow reserve (2.8±0.8; 95%CI: 2.6−3.0) excluding underlying CAD. Simple regression analysis revealed a significant correlation between absolute CPTMBF and triglyceride level (rho = −0.32, p = 0.024) fasting blood insulin (rho = −0.43, p = 0.0024), HOMA-IR (rho = −0.39, p = 0.007) and PFV (rho = −0.52, p = 0.0001). MBF response to adenosine was only correlated with PFV (rho = −0.32, p = 0.026). On multivariate regression analysis PFV emerged as the only significant predictor of MBF response to CPT (p = 0.002).Conclusion: PFV is significantly correlated with endothelium-dependent coronary vasomotion. High PF burden might negatively influence MBF response to CPT, as well as to adenosine stress, even in persons with normal hyperemic myocardial perfusion imaging, suggesting a link between PF and future cardiovascular events. While outside-to-inside adipokines secretion through the arterial wall has been described, our results might suggest an effect upon NO-dependent and -independent vasodilatation. Further studies are needed to elucidate this mechanism.

Coronary artery disease screening in diabetic patients: how good is guideline adherence?

INTRODUCTION: Diabetic patients are at high risk for coronary artery disease (CAD), which is the leading cause of death in this population. The Swiss Society of Endocrinology-Diabetology (SSED) recommends CAD screening for diabetic patients with > or = 2 additional cardiovascular risk factors (CVRF), by stress echocardiography (SE) or myocardial perfusion imaging (MPI). The aim of this study was to assess the application of these guidelines and the treatment of CVRF in the diabetes outpatient clinics of the five Swiss University Hospitals. METHODS: The study was initiated in Lausanne and the study questionnaires were circulated to the endocrinologists of the five Swiss University Hospitals. Practitioners were asked to include consecutive patients attending the diabetes outpatient clinics over one month. Prevalence of CAD, screening methods for CAD, prevalence of CVRF, biological analyses over the last 6 months and medical therapy were recorded. RESULTS: A total of 302 subjects were included. The mean age was 53 +/- 14 years, 68% had type 2 diabetes, 27% type 1 and 5% other types. Among T2DM with > or = 2 CVRF, 45% were screened for CAD according to SSED guidelines. In T2DM 25% had blood pressure < or = 130/80 mm Hg, 15% a lipid profile within target, 23% HbA1c < or = 7.0%. Overall, 2% achieved all 3 targets. CONCLUSIONS: Only 45% of T2DM with > or = 2 CVRF were screened for CAD according to SSED guidelines and 2% of T2DM had proper control over all CVRF. Efforts are still necessary to improve CAD prevention and screening of diabetic patients in Swiss University Hospitals.

Efficiency of coronary artery disease screening guidelines in asymptomatic and atypical chest pain type 2 diabetic patients

RESUME Objectifs. Évaluer la prévalence de maladie coronarienne chez les patients diabétiques de type 2 asymptomatiques ou avec angor atypique selon les recommandations américaines de l'American Diabetes Association et de l'American College of Cardiology. Méthodes. Cent cinquante-quatre patients diabétiques de type 2 asymptomatiques ou avec angor atypique et présentant au minimum 2 facteurs de risque cardio-vasculaires additionnels ont été dépistés par échocardiographie de stress (71%, n=109), scintigraphie myocardique de perfusion (26%, n=40) ou l'association des 2 examens (3%, n=5). Résultats. L'échocardiographie de stress s'est révélée positive chez 16 patients (14%) et 14 ont eu une coronarographie révélant des sténoses significatives chez 12 (86%). La scintigraphie myocardique de perfusion était positive chez 16 patients (36%). Huit patients ont eu une coronarographie et 4 (50%) présentaient des sténoses significatives. Au total, 31 patients (20%) ont montré des signes d'ischémie lors de l'examen non-invasif et 15 (10%) ont présenté des sténoses significatives à la coronarographie. Les facteurs prédictifs indépendants de la maladie coronarienne étaient le tabagisme (OR 6.5, p=0.05), la microalbuminurie (OR 3.9, p=0.03), ainsi que les souffles fémoraux (OR 17.1, p=0.008). Conclusions. En suivant les recommandations américaines, un patient sur cinq présentait une ischémie lors des examens non-invasifs, tandis que 1 sur 10 avait des sténoses significatives à la coronarographie. L'analyse multivariée suggère que des marqueurs des complications micro- et macro-vasculaires en combinaison avec des facteurs de risque cardio-vasculaire classiques pourraient améliorer le pouvoir diagnostic de ces recommandations. SUMMARY Aims. We evaluated the prevalence of coronary artery disease in asymptomatic and atypical chest pain type 2 diabetic patients according to the American Diabetes Association and American College of Cardiology guidelines. Methods. Asymptomatic or atypical chest pain type 2 diabetic patients (n=154), with at least two additional cardiovascular risk factors, were screened for coronary artery disease using stress echocardiography (71%, n=109), myocardial perfusion imaging (26%, n=40) or both (3%, n=5). Results. Stress echocardiography was positive in 16 patients (14%) and 14 had a coronary angiography, revealing significant stenoses in 12 (86%). Myocardial perfusion imaging was positive in 16 patients (36%). Eight patients underwent angiography and 4 (50%) presented significant stenoses. Overall, 31 patients (20%) demonstrated signs of ischemia on non-invasive tests and 15 (10%) presented significant stenoses on coronary angiography. Independent predictors of coronary artery disease were smoking (OR 6.5, p=0.05), microalbuminuria (OR 3.9, p=0.03) and femoral murmur (OR 17.1, p=0.008). Conclusions. Following the guidelines, one in five diabetic patient presented ischemia on noninvasive tests, while one in ten presented significant coronary stenoses. Multivariate analysis suggests that adding markers of micro- and macro-vascular complications to classical cardiovascular risk factors may enhance the diagnostic efficiency of the guidelines.

Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse.

Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response important for myocardial healing, but which may also contribute to adverse ventricular remodelling. Such inflammation is initiated by molecular danger signals released by damaged myocardium, which induce innate immune responses by activating toll-like receptors (TLRs). Detrimental roles have been recently reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore evaluated the role of TLR5, expressed at high level in the heart, in the development of myocardial damage and inflammation acutely triggered by MIR. TLR5-/- and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h reperfusion). We measured infarct size, markers of cardiac oxidative stress, myocardial phosphorylation state of mitogen-activated protein (MAP) kinases and AKT, expression levels of chemokines and cytokines in the heart and plasma, as well as cardiac function by echography and conductance volumetry. TLR5-deficient mice had normal cardiac morphology and function under physiological conditions. After MIR, the absence of TLR5 promoted an increase in infarct size and myocardial oxidative stress. Lack of TLR5 fostered p38 phosphorylation, reduced AKT phosphorylation and markedly increased the expression of inflammatory cytokines, whereas it precipitated acute LV (left ventricle) dysfunction. Therefore, contrary to the detrimental roles of TLR2, TLR3 and TLR4 in the infarcted heart, TLR5 is important to limit myocardial damage, inflammation and functional compromise after MIR.

Apports de la médecine nucléaire en cardiologie préventive: l'exemple du syndrome métabolique [Value of nuclear medicine in preventive cardiology: the metabolic syndrome example]

Metabolic syndrome represents a grouping of risk factors closely linked to cardiovascular diseases and diabetes. At first, nuclear medicine has no direct application in cardiology at the level of primary prevention, but positron emission tomography is a non invasive imaging technique that can assess myocardial perfusion as well as the endothelium-dependent coronary vasomotion--a surrogate marker of cardiovascular event rate--thus finding an application in studying coronary physiopathology. As the prevalence of the metabolic syndrome is still unknown in Switzerland, we will estimate it from data available in the frame of a health promotion program. Based on the deleterious effect on the endothelium already observed with two components, we will estimate the number of persons at risk in Switzerland.

Vascular postpneumonectomy syndrome: inferior vena cava and pulmonary vein compression as unusual cause for platypnea-orthodeoxia following pneumonectomy

Background: Excessive mediastinal shift into the vacated thoracic cavity after pneumonectomy can result in dyspnea without hypoxemia by compression of the tracheobronchial tree, a phenomenon called postpneumonectomy syndrome. More rarely hypoxemia in upright position (platypnea-orthodeoxia syndrome, POS) after pneumonectomy can result from re-opening of an atrial right-to-left shunt through a patent foramen ovale (PFO) due to mediastinal distorsion. Review of literature also shows a unique report of pulmonary veins stenosis resulting in POS without intracardiac shunt after pneumonectomy. Methods: We report the case of a 32-year-old woman who presented POS 6 months after right pneumonectomy for destroyed lung post tuberculosis. Results: The patient described severe dyspnea disappearing when lying. SpO2 decreased from 94% when lying to 60% sitting. Transthoracic echocardiography (TTE) suspected a possible PFO. We first tried to highlight clinical repercussions of PFO by noninvasive exams. Hyperoxia shunt quantification was not tolerated because of increased dyspnea in sitting position. Contrast bubbles TTE was difficult because of the important mediastinal shift but identified only rare left heart bubbles with/without Valsalva both in lying and sitting position, excluding a significant right-to-left shunt. A lung perfusion scintigraphy (injection while sitting) confirmed the absence of systemic isotope uptake. Computed tomographic pulmonary angiography (angio-CT) revealed a stretched but not stenosed left main bronchus, while the shift of the heart into the right cavity was major. Pulmonary angiography did not show embolism but revealed compression of the inferior vena cava (IVC) with impaired venous return to the right heart, as well as compression of the left pulmonary veins. There was no arteriovenous shunt. Cardiac MRI showed torsion of IVC at the level of the diaphragm, and strong atrial contraction contributing to a passive filling of the RV, while the right ventricle was normal. Right catheterism showed major hemodynamic disturbances with negative diastolic pressure in right heart cavities (atrium -12 mm Hg ventricle pressure -7 mm Hg). SaO2 measured in the pulmonary artery decreased from 58% when lying to 45% sitting. Conclusion: We described here an exceedingly rare and complex mechanism explaining POS after right pneumonectomy. Mediastinal repositioning with a silicone breast implant of appropriate size has been scheduled.

Impact of lung function changes after induction radiochemotherapy on resected T4 non-small cell lung cancer outcome.

BACKGROUND: Induction radiochemotherapy, followed by resection, for T4 non-small cell lung cancer, has shown promising long-term survival but may be associated with increased postoperative morbidity and death, depending on patient selection. Here, we determined the effect of induction radiochemotherapy on pulmonary function and whether postinduction pulmonary function changes predict hospital morbidity and death and long-term survival. METHODS: A consecutive prospective cohort of 72 patients with T4 N0-2 M0 non-small cell lung cancer managed by radiochemotherapy, followed by resection, is reported. All patients underwent thoracoabdominal computed tomography or fusion positron emission tomography-computed tomography, brain imaging, mediastinoscopy, echocardiography, ventilation-perfusion scintigraphy, and pulmonary function testing before and after induction therapy. Resection was performed if the postoperative forced expiratory volume in 1 second and diffusion capacity of the lung for carbon monoxide exceeded 30% predicted and if the postoperative maximum oxygen consumption exceeded 10 mL/kg/min. RESULTS: The postoperative 90-day mortality rate was 8% (lobectomy, 2%; pneumonectomy, 21%; p=0.01). All deaths after pneumonectomy occurred after right-sided procedures. The 3-year and 5-year survival was 50% (95% confidence interval, 36% to 62%) and 45% (95% confidence interval, 31% to 57%) and was significantly associated with completeness of resection (p=0.004) and resection type (pneumonectomy vs lobectomy, p=0.01). There was no correlation between postinduction pulmonary function changes and postoperative morbidity or death or long-term survival in patients managed by lobectomy or pneumonectomy. CONCLUSIONS: In properly selected patients with T4 N0-2 M0 non-small cell lung cancer, resection after induction radiochemotherapy can be performed with a reasonable postoperative mortality rate and long-term survival, provided the resection is complete and a right-sided pneumonectomy is avoided. Postinduction pulmonary function changes did not correlate with postoperative morbidity or death or with long-term outcome.

Angiotensin II favors progression to heart failure in diabetic hearts: role of myocardial fatty acid oxidation downregulation

Purpose: Diabetic myocardium is particularly vulnerable to develop heart failure in response to chronic stress conditions including hypertension or myocardial infarction. We have recently observed that angiotensin II (Ang II)-mediated downregulation of the fatty acid oxidation pathway favors occurrence of heart failure by myocardial accumulation of lipids (lipotoxicity). Because diabetic heart is exposed to high levels of circulating fatty acid, we determined whether insulin resistance favors development of heart failure in mice with Ang II-mediated myocardial remodeling.Methods: To study the combined effect of diabetes and Ang II-induced heart remodeling, we generated leptin-deficient/insulin resistant (Lepob/ob) mice with cardiac targeted overexpression of angiotensinogen (TGAOGN). Left ventricular (LV) failure was indicated by pulmonary congestion (lung weight/tibial length>+2SD of wild-type mice). Myocardial metabolism and function were assessed during in vitro isolated working heart perfusion.Results: Forty-eight percent of TGAOGN mice without insulin resistance exhibited pulmonary congestion at the age of 6 months associated with increased myocardial BNP expression (+375% compared with WT) and reduced LV power (developed pressure x cardiac output; -15%). The proportion of mice presenting heart failure was markedly increased to 71% in TGAOGN mice with insulin resistance (TGAOGN/Lepob/ob). TGAOGN/Lepob/ob mice with heart failure exhibited further increase of BNP compared with failing non-diabetic TGAOGN mice (+146%) and further reduction of cardiac power (-59%). Mice with insulin resistance alone (Lepob/ob) did not exhibit signs of heart failure or LV dysfunction. Myocardial fatty acid oxidation measured during in vitro perfusion was markedly increased in non-failing hearts from Lepob/ob mice (+380% compared with WT) and glucose oxidation decreased (-72%). In contrast, fatty acid and glucose oxidation did not differ from Lepob/ob mice in hearts from TGAOGN/Lepob/ob mice without heart failure. However, both fatty acid and glucose oxidation were markedly decreased (-47% and -48%, respectively, compared with WT/Lepob/+) in failing hearts from TGAOGN/Lepob/ob mice. Reduction of fatty acid oxidation was associated with marked reduction of protein expression of a number of regulatory enzymes implied in fatty acid oxidation.Conclusions: Insulin resistance favors the progression to heart failure during chronic exposure of the myocardium to Ang II. Our results are compatible with a role of Ang II-mediated downregulation of fatty acid oxidation, potentially promoting lipotoxicity.

Local transient myocardial liposomal gene transfer of inducible nitric oxide synthase does not aggravate myocardial function and fibrosis and leads to moderate neovascularization in chronic myocardial ischemia in pigs.

Microcirculation (2010) 17, 69-78. doi: 10.1111/j.1549-8719.2010.00002.x Abstract Background: This study was designed to explore the effect of transient inducible nitric oxide synthase (iNOS) overexpression via cationic liposome-mediated gene transfer on cardiac function, fibrosis, and microvascular perfusion in a porcine model of chronic ischemia. Methods and Results: Chronic myocardial ischemia was induced using a minimally invasive model in 23 landrace pigs. Upon demonstration of heart failure, 10 animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection and 13 animals received a sham procedure to serve as control. The efficacy of this iNOS-gene-transfer was demonstrated for up to 7 days by reverse transcriptase-polymerase chain reaction in preliminary studies. Four weeks after iNOS transfer, magnetic resonance imaging showed no effect of iNOS overexpression on cardiac contractility at rest and during dobutamine stress (resting ejection fraction: control 27%, iNOS 26%; P = ns). Late enhancement, infarct size, and the amount of fibrosis were similar between groups. Although perfusion and perfusion reserve in response to adenosine and dobutamine were not significantly modified by iNOS-transfer, both vessel number and diameter were significantly increased in the ischemic area in the iNOS-treated group versus control (point score: control 15.3, iNOS 34.7; P < 0.05). Conclusions: Our findings demonstrate that transient iNOS overexpression does not aggravate cardiac dysfunction or postischemic fibrosis, while potentially contributing to neovascularization in the chronically ischemic heart.

Determination of displacement, stress- and strain-distribution in the human heart: a FE-model on the basis of MR imaging.

The determination of characteristic cardiac parameters, such as displacement, stress and strain distribution are essential for an understanding of the mechanics of the heart. The calculation of these parameters has been limited until recently by the use of idealised mathematical representations of biventricular geometries and by applying simple material laws. On the basis of 20 short axis heart slices and in consideration of linear and nonlinear material behaviour we have developed a FE model with about 100,000 degrees of freedom. Marching Cubes and Phong's incremental shading technique were used to visualise the three dimensional geometry. In a quasistatic FE analysis continuous distribution of regional stress and strain corresponding to the endsystolic state were calculated. Substantial regional variation of the Von Mises stress and the total strain energy were observed at all levels of the heart model. The results of both the linear elastic model and the model with a nonlinear material description (Mooney-Rivlin) were compared. While the stress distribution and peak stress values were found to be comparable, the displacement vectors obtained with the nonlinear model were generally higher in comparison with the linear elastic case indicating the need to include nonlinear effects.

An adapted model of ex vivo vein perfusion: the key to understand vessel wall remodeling

Objective: Saphenous vein graft bypass remains the salvage option when¦endovascular procedure has failed or was contraindicated due to extensive¦occlusive lesions. However, pathological wall remodeling leading leading to¦graft failure is one of the most limiting factors of this therapy. Therefore, the¦understanding of this remodeling process of human vein is essential to the design¦of future effective therapeutics and it requires an adapted model of ex-vivo vein¦perfusion.¦Methods: We have developed an ex vivo vein support system (EVVSS), which¦uses standardized and controlled hemodynamic parameters for the pulsatile¦perfusion of saphenous vein segments. The morphological and molecular¦parameters involved in the remodeling process under an arterial shear stress¦associated to low (7 mm Hg) or high (70 mm Hg) pressure conditions can be¦analyzed.¦Results: Histomorphometric analysis showed that the vein segments perfused¦during 7 days under high pressure undergo a significant neointima development¦compared to veins exposed to low pressure conditions. The application of an¦arterial shear stress in the vein under low pressure induced an elevation of the¦MMP-2 and MMP-9 expression, activity and transcription. The application of¦higher pressure is associated to increased MMP2 expression and transcription¦and MMP9 transcription. TIMP1 expression and transcription were initiated by¦the application of an arterial shear stress but not modified by the modification¦of the pressure. However, TIMP2 expression was increased under high¦pressure conditions but its transcription was inhibited by arterial shear stress,¦independently of the pressure. The values of transcription and expression of¦PAI-1 were not modified by high pressure. Eph-B4 transcription and expression¦were significantly decreased under arterial shear stress.¦Conclusion: These data show that our EVVSS is a valuable setting to study¦ex vivo remodeling of human saphenous veins submitted to arterial conditions.¦The intimal hyperplasia as well as MMP 2, 9 and TIMP 2 seem to be influenced¦by the pressure.