Self-expanding mini-cannula for remote perfusion with pediatric scenarios.

The aim of this report is to address the benefits of the minimal invasive venous drainage in a pediatric cardio surgical scenario. Juvenile bovine experiments (67.4+/-11 kg) were performed. The right atrium was cannulated in a trans-jugular way by using the self-expandable (Smart Stat, 12/20F, 430 mm) venous cannula (Smartcannula LLC, Lausanne, Switzerland) vs. a 14F 250 mm (Polystan Lighthouse) standard pediatric venous cannula. Establishing the cardiopulmonary bypass (CPB), the blood flows were assessed for 20 mmHg, 30 mmHg and 40 mmHg of driving pressure. Venous drainage (flow in l/min) at 20 mmHg, 30 mmHg, and 40 mmHg drainage load was 0.26+/-0.1, 0.35+/-0.2 and 0.28+/-0.08 for the 14F standard vs. 1.31+/-0.22, 1.35+/-0.24 and 1.9+/-0.2 for the Smart Stat 12/20F cannula. The 43 cm self-expanding 12/20F Smartcannula outperforms the 14F standard cannula. The results described herein allow us to conclude that usage of the self-expanding Smartcannula also in the pediatric patients improves the flow and the drainage capacity, avoiding the insufficient and excessive drainage. We believe that similar results may be expected in the clinical settings.

Declining stroke and myocardial infarction mortality between 1989 and 2010 in a country of the African region.

BACKGROUND AND PURPOSE: In low- and middle-income countries, the total burden of cardiovascular diseases is expected to increase due to demographic and epidemiological transitions. However, data on cause-specific mortality are lacking in sub-Saharan Africa. Seychelles is one of the few countries in the region where all deaths are registered and medically certified. In this study, we examine trends in mortality for stroke and myocardial infarction (MI) between 1989 and 2010. METHODS: Based on vital statistics, we ascertained stroke and MI as the cause of death if appearing in any of the 4 fields for immediate, intermediate, underlying, and contributory causes in death certificates. RESULTS: Mortality rates (per 100 000, age-standardized to World Health Organization standard population) decreased from 1669/710 (men/women) in 1989 to 1991 to 1113/535 in 2008-10 for all causes, from 250/140 to 141/86 for stroke, and from 117/51 to 59/24 for MI, corresponding to proportionate decreases of 33%/25% for all-cause mortality, 44%/39% for stroke, and 50%/53% for MI over 22 years. The absolute number of stroke and MI deaths did not increase over time. In 2008 to 2010, the median age of death was 65/78 years (men/women) for all causes, 68/78 for stroke, and 66/73 for MI. CONCLUSIONS: Between 1989 and 2010, age-standardized stroke and MI mortality decreased markedly and more rapidly than all-cause mortality. The absolute number of cardiovascular disease deaths did not increase over time because the impact of population aging was fully compensated by the decline in cardiovascular disease mortality. Stroke mortality remained high, emphasizing the need to strengthen cardiovascular disease prevention and control.

Incremental Prognostic Value of Myocardial Blood Flow Quantification with Rb-82 Cardiac PET in Patients With Known or Suspected CAD

Rb-82cardiac PET has been used to non-invasively assess myocardial blood flow (MBF)and myocardial flow reserve (MFR). The impact of MBF and MFR for predictingmajor adverse cardiovascular events (MACE) has not been investigated in aprospective study, which was our aim. MATERIAL AND METHODS: In total, 280patients (65±10y, 36% women) with known or suspected CAD were prospectivelyenrolled. They all underwent both a rest and adenosine stress Rb-82 cardiacPET/CT. Dynamic acquisitions were processed with the FlowQuant 2.1.3 softwareand analyzed semi-quantitatively (SSS, SDS) and quantitatively (MBF, MFR) andreported using the 17-segment AHA model. Patients were stratified based on SDS,stress MBF and MFR and allocated into tertiles. For each group, annualizedevent rates were computed by dividing the number of annualized MACE (cardiacdeath, myocardial infarction, revascularisation or hospitalisation forcardiac-related event) by the sum of individual follow-up periods in years.Outcome were analysed for each group using Kaplan-Meier event-free survivalcurves and compared using the log-rank test. Multivariate analysis wasperformed in a stepwise fashion using Cox proportional hazards regressionmodels (p<0.05 for model inclusion). RESULTS: In a median follow-up of 256days (range 168-440d), 44 MACE were observed. Ischemia (SDS≥2) was observed in95 patients who had higher annualized MACE rate as compared to those without(55% vs. 9.8%, p<0.0001). The group with the lowest MFR tertile (MFR<1.76)had higher MACE rate than the two highest tertiles (51% vs. 9% and 14%,p<0.0001). Similarly, the group with the lowest stress MBF tertile(MBF<1.78mL/min/g) had the highest annualized MACE rate (41% vs. 26% and 6%,p=0.0002). On multivariate analysis, the addition of MFR or stress MBF to SDSsignificantly increased the global χ2 (from 56 to 60, p=0.04; and from56 to 63, p=0.01). The best prognostic power was obtained in a model combiningSDS (p<0.001) and stress MBF (p=0.01). Interestingly, the integration ofstress MBF enhanced risk stratification even in absence of ischemia.CONCLUSIONS: Quantification of MBF or MFR in Rb-82 cardiac PET/CT providesindependent and incremental prognostic information over semi-quantitativeassessment with SDS and is of value for risk stratification.

Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester.

OBJECTIVE: To investigate the influence of obesity on the regulation of myocardial glucose metabolism following protein kinase C (PKC) activation in obese (fa/fa) and lean (Fa/?) Zucker rats. DESIGN: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) for different time periods prior to the evaluation of PKC and GLUT-4 translocation. For metabolic studies isolated hearts from 48 h starved Zucker rats were perfused with an erythrocytes-enriched buffer containing increased concentrations (10-100 nM) of PMA. MEASUREMENTS: Immunodetectable PKC isozymes and GLUT-4 were determined by Western blots. Glucose oxidation and glycolysis were evaluated by measuring the myocardial release of 14CO2 and 3H2O from [U-14C]glucose and [5-3H]glucose, respectively. RESULTS: PMA (200 nM) induced maximal translocation of ventricular PKCalpha from the cytosol to the membranes within 10 min. This translocation was 2-fold lower in the heart from obese rats when compared to lean rats. PMA also induced a significant translocation of ventricular GLUT-4 from the microsomal to the sarcolemmal fraction within 60 min in lean but not in obese rats. Rates of basal cardiac glucose oxidation and glycolysis in obese rats were approximately 2-fold lower than those of lean rats. Perfusion with increasing concentrations of PMA (10-100 nM) led to a significant decrease of cardiac glucose oxidation in lean but not in obese rats. CONCLUSION: Our results show that in the heart of the genetically obese Zucker rat, the impairment in PKCalpha activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.

The region makes the difference: disparities in management of acute myocardial infarction within Switzerland.

BACKGROUND: In Switzerland, health policies are decided at the local level, but little is known regarding their impact on the management of acute myocardial infarction (AMI). In this study, we assessed geographical differences within Switzerland regarding management of AMI. DESIGN: Cross-sectional study. METHODS: Swiss hospital discharge database for period 2007-2008 (26,204 discharges from AMI). Seven Swiss regions (Leman, Mittelland, Northwest, Zurich, Central, Eastern, and Ticino) were analysed. RESULTS: Almost 53.7% of discharges from AMI were managed in a single hospital, ranging from 62.1% (Leman) to 31.6% (Ticino). The highest intensive care unit admission rate was in Leman (69.4%), the lowest (16.9%) in Ticino (Swiss average: 36.0%). Intracoronary revascularization rates were highest in Leman (51.1%) and lowest (30.9%) in Central Switzerland (average: 41.0%). Bare (non-drug-eluting) stent use was highest in Leman (61.4%) and lowest (16.9%) in Ticino (average: 42.1%), while drug-eluting stent use was highest (83.2%) in Ticino and lowest (38.6%) in Leman (average: 57.9%). Coronary artery bypass graft rates were highest (4.8%) in Ticino and lowest (0.5%) in Eastern Switzerland (average: 2.8%). Mechanical circulatory assistance rates were highest (4.2%) in Zurich and lowest (0.5%) in Ticino (average: 1.8%). The differences remained after adjusting for age, single or multiple hospital management, and gender. CONCLUSIONS: In Switzerland, significant geographical differences in management and revascularization procedures for AMI were found.

Trends in hospital discharges, management and in-hospital mortality from acute myocardial infarction in Switzerland between 1998 and 2008.

BACKGROUND: Since the late nineties, no study has assessed the trends in management and in-hospital outcome of acute myocardial infarction (AMI) in Switzerland. Our objective was to fill this gap. METHODS: Swiss hospital discharge database for years 1998 to 2008. AMI was defined as a primary discharge diagnosis code I21 according to the ICD10 classification. Invasive treatments and overall in-hospital mortality were assessed. RESULTS: Overall, 102,729 hospital discharges with a diagnosis of AMI were analyzed. The percentage of hospitalizations with a stay in an Intensive Care Unit decreased from 38.0% in 1998 to 36.2% in 2008 (p for trend < 0.001). Percutaneous revascularizations increased from 6.0% to 39.9% (p for trend < 0.001). Bare stents rose from 1.3% to 16.6% (p for trend < 0.001). Drug eluting stents appeared in 2004 and increased to 23.5% in 2008 (p for trend < 0.001). Coronary artery bypass graft increased from 1.0% to 3.0% (p for trend < 0.001). Circulatory assistance increased from 0.2% to 1.7% (p for trend < 0.001). Among patients managed in a single hospital (not transferred), seven-day and total in-hospital mortality decreased from 8.0% to 7.0% (p for trend < 0.01) and from 11.2% to 10.1%, respectively. These changes were no longer significant after multivariate adjustment for age, gender, region, revascularization procedures and transfer type. After multivariate adjustment, differing trends in revascularization procedures and in in-hospital mortality were found according to the geographical region considered. CONCLUSION: In Switzerland, a steep rise in hospital discharges and in revascularization procedures for AMI occurred between 1998 and 2008. The increase in revascularization procedures could explain the decrease in in-hospital mortality rates.

Assessment of distribution and evolution of mechanical dyssynchrony in a porcine model of myocardial infarction by cardiovascular magnetic resonance.

BACKGROUND: We sought to investigate the relationship between infarct and dyssynchrony post- myocardial infarct (MI), in a porcine model. Mechanical dyssynchrony post-MI is associated with left ventricular (LV) remodeling and increased mortality. METHODS: Cine, gadolinium-contrast, and tagged cardiovascular magnetic resonance (CMR) were performed pre-MI, 9 ± 2 days (early post-MI), and 33 ± 10 days (late post-MI) post-MI in 6 pigs to characterize cardiac morphology, location and extent of MI, and regional mechanics. LV mechanics were assessed by circumferential strain (eC). Electro-anatomic mapping (EAM) was performed within 24 hrs of CMR and prior to sacrifice. RESULTS: Mean infarct size was 21 ± 4% of LV volume with evidence of post-MI remodeling. Global eC significantly decreased post MI (-27 ± 1.6% vs. -18 ± 2.5% (early) and -17 ± 2.7% (late), p < 0.0001) with no significant change in peri-MI and MI segments between early and late time-points. Time to peak strain (TTP) was significantly longer in MI, compared to normal and peri-MI segments, both early (440 ± 40 ms vs. 329 ± 40 ms and 332 ± 36 ms, respectively; p = 0.0002) and late post-MI (442 ± 63 ms vs. 321 ± 40 ms and 355 ± 61 ms, respectively; p = 0.012). The standard deviation of TTP in 16 segments (SD16) significantly increased post-MI: 28 ± 7 ms to 50 ± 10 ms (early, p = 0.012) to 54 ± 19 ms (late, p = 0.004), with no change between early and late post-MI time-points (p = 0.56). TTP was not related to reduction of segmental contractility. EAM revealed late electrical activation and greatly diminished conduction velocity in the infarct (5.7 ± 2.4 cm/s), when compared to peri-infarct (18.7 ± 10.3 cm/s) and remote myocardium (39 ± 20.5 cm/s). CONCLUSIONS: Mechanical dyssynchrony occurs early after MI and is the result of delayed electrical and mechanical activation in the infarct.

Using 80 kVp versus 120 kVp in perfusion CT measurement of regional cerebral blood flow.

Perfusion CT studies of regional cerebral blood flow (rCBF), involving sequential acquisition of cerebral CT sections during IV contrast material administration, have classically been reported to be achieved at 120 kVp. We hypothesized that using 80 kVp should result in the same image quality while significantly lowering the patient's radiation dose, and we evaluated this assumption. In five patients undergoing cerebral CT survey, one section level was imaged at 120 kVp and 80 kVp, before and after IV administration of iodinated contrast material. These four cerebral CT sections obtained in each patient were analyzed with special interest to contrast, noise, and radiation dose. Contrast enhancement at 80 kVp is significantly increased (P < .001), as well as contrast between gray matter and white matter after contrast enhancement (P < .001). Mean noise at 80 kVp is not statistically different (P = .042). Finally, performance of perfusion CT studies at 80 kVp, keeping mAs constant, lowers the radiation dose by a factor of 2.8. We, thus, conclude that 80 kVp acquisition of perfusion CT studies of rCBF will result in increased contrast enhancement and should improve rCBF analysis, with a reduced patient's irradiation.

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

PURPOSE: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). METHODS: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. RESULTS: There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = -0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 +/- 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 +/- 0.24 vs. 0.74 +/- 0.23 and 1.82 +/- 0.50 vs. 1.95 +/- 0.51 ml/g/min; p < or = 0.05, respectively) and also during CPT in DM but less pronounced (0.81 +/- 0.24 vs. 0.83 +/- 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = -0.36, p < or = 0.014; r = -0.46, p < or = 0.007; and r = -0.33, p < or = 0.041, respectively). CONCLUSIONS: The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.

Spiral MR myocardial tagging.

In the present study, complementary spatial modulation of magnetization (CSPAMM) myocardial tagging was extended with an interleaved spiral imaging sequence. The use of a spiral sequence enables the acquisition of grid-tagged images with a tagline distance as low as 4 mm in a single breath-hold. Alternatively, a high temporal resolution of 77 frames per second was obtained with 8-mm grid spacing. Ten healthy adult subjects were studied. With this new approach, high-quality images can be obtained and the tags persist throughout the entire cardiac cycle.

The Smartcanula: a new tool for remote access perfusion in limited access cardiac surgery.

Devices for venous cannulation have seen significant progress over time: the original, rigid steel cannulas have evolved toward flexible plastic cannulas with wire support that prevents kinking, very thin walled wire wound cannulas allowing for percutaneous application, and all sorts of combinations. In contrast to all these rectilinear venous cannula designs, which present the same cross-sectional area over their entire intravascular path, the smartcanula concept of "collapsed insertion and expansion in situ" is the logical next step for venous access. Automatically adjusting cross-sectional area up to a pre-determined diameter or the vessel lumen provides optimal flow and ease of use for both, insertion and removal. Smartcanula performance was assessed in a small series of patients (76 +/- 17 kg) undergoing redo procedures. The calculated target pump flow (2.4 L/min/m2) was 4.42 +/- 61 L/ min. Mean pump flow achieved during cardiopulmonary bypass was 4.84 +/- 87 L/min or 110% of the target. Reduced atrial chatter, kink resistance in situ, and improved blood drainage despite smaller access orifice size, are the most striking advantages of this new device. The benefits of smart cannulation are obvious in remote cannulation for limited access cardiac surgery, but there are many other cannula applications where space is an issue, and that is where smart cannulation is most effective.

Augmented myocardial methionine-enkephalin in a murine model of cardiac angiotensin II-overexpression.

INTRODUCTION: The endogenous opioid system has been reported to interact with both the cardiac sympathetic and renin-angiotensin systems in exerting a local regulatory action on the heart. The goal of this investigation was to examine how cardiac levels of enkephalin production are altered in the development of normotensive primary hypertrophy due to elevated intra-cardiac angiotensin II (Ang II) production. METHODS: Atrial and ventricular methionine-enkephalin (ME) levels were measured by quantitative radioimmunoassay in 14 and 28-week-old male transgenic mice (TG1306/1R) and control mice. The TG1306/1R exhibit cardiac specific Ang II overexpression and cardiac hypertrophy, but not hypertension. RESULTS: TG1306/1R mice had significantly higher heart/body weight ratios (15-20%) than control littermates at both 14 (p=0.02) and 28 weeks (p=0.04). Relative to controls, ME content was significantly elevated (approximately two-fold) in atria and ventricles in the older 28-week TG1306/1R mice only. A significant inverse correlation between heart size and ME level was observed for 28-week TG1306/1R only. CONCLUSIONS: We have provided evidence that a marked elevation of myocardial enkephalin level is observed in the established (but not early) phase of cardiac hypertrophy associated with cardiac-specific Ang II-overexpression. This study identifies a potentially important relationship between two endogenous peptidergic signalling systems involved in the regulation of growth and function of the hypertrophic heart.

Comparativecost-effectivenessanalyses of cardiacmagneticresonanceimaging versus invasive coronary angiography combined with fractional flow reserve testing to diagnose ischemia in coronary artery disease

Introduction: According to guidelines, patients with coronary artery disease (CAD) should undergo revascularization if myocardial ischemia is present. While coronary angiography (CXA) allows the morphological assessment of CAD, the fractional flow reserve (FFR) has proved to be a complementary invasive test to assess the functional significance of CAD, i.e. to detect ischemia. Perfusion Cardiac Magnetic Resonance (CMR) has turned out to be a robust non-invasive technique to assess myocardial ischemia. The objective: is to compare the cost-effectiveness ratio - defined as the costs per patient correctly diagnosed - of two algorithms used to diagnose hemodynamically significant CAD in relation to the pretest likelihood of CAD: 1) aCMRto assess ischemia before referring positive patients to CXA (CMR + CXA), 2) a CXA in all patients combined with a FFR test in patients with angiographically positive stenoses (CXA + FFR). Methods: The costs, evaluated from the health care system perspective in the Swiss, German, the United Kingdom (UK) and the United States (US) contexts, included public prices of the different tests considered as outpatient procedures, complications' costs and costs induced by diagnosis errors (false negative). The effectiveness criterion wasthe ability to accurately identify apatient with significantCAD.Test performancesused in the model were based on the clinical literature. Using a mathematical model, we compared the cost-effectiveness ratio for both algorithms for hypothetical patient cohorts with different pretest likelihood of CAD. Results: The cost-effectiveness ratio decreased hyperbolically with increasing pretest likelihood of CAD for both strategies. CMR + CXA and CXA + FFR were equally costeffective at a pretest likelihood of CAD of 62% in Switzerland, 67% in Germany, 83% in the UK and 84% in the US with costs of CHF 5'794, Euros 1'472, £ 2'685 and $ 2'126 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. Implications for the health care system/professionals/patients/society These results facilitate decision making for the clinical use of new generations of imaging procedures to detect ischemia. They show to what extent the cost-effectiveness to diagnose CAD depends on the prevalence of the disease.