Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model. MATERIALS AND METHODS: Nine adult sheep were included. Temperature probes were introduced into the frontal and temporal brain cortices bilaterally. The cooling catheter system was introduced into a common carotid artery. Selective blood cooling was applied for 180 minutes. Systemic and local brain temperatures were measured during cooling and rewarming. Common carotid artery diameters and flow were measured angiographically and by Doppler sonography. RESULTS: The common carotid artery diameter was between 6.7 and 7.3 mm. Common carotid artery blood flow velocities increased moderately during cooling and after catheter removal. Maximum cerebral cooling in the ipsilateral temporal cortex was -4.7°C (95% CI, -5.1 to -4.0°C). Ipsilateral brain temperatures dropped significantly faster and became lower compared with the contralateral cortex with maximum temperature difference of -1.3°C (95% CI, -1.5 to -1.0°C; P < .0001) and compared with systemic temperature (-1.4°C; 95% CI, -1.7 to -1.0°C; P < .0001). CONCLUSIONS: Sheep proved a feasible animal model for the intracarotid cooling catheter. Fast induction of selective mild hypothermia was achieved within the cooled cerebral hemisphere, with stable temperature gradients in the contralateral brain and systemic blood. Further studies are required to demonstrate any therapeutic benefit of selective cerebral cooling in a stroke model.

Combined Selective Cerebral Hypothermia and Mechanical Artery Recanalization in Acute Ischemic Stroke: In Vitro Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment for patients with ischemic stroke. Selective, intracarotid blood cooling may initiate rapid and early brain hypothermia, reduce systemic effects, and allow combined endovascular mechanical thrombectomy. For this approach, a balloon cooling catheter system was designed and studied in vitro to optimize its cooling performance. MATERIALS AND METHODS: Computational fluid dynamics of blood cooling was performed within the common carotid artery lumen by using 3 different catheter designs (1-, 2-, and 4-balloon array). On the basis of these results, a first catheter prototype was manufactured, and its heat-exchange performance was tested in an artificial in vitro circulation simulating the common carotid artery lumen at different flow rates (inflow temperature of 37°C). RESULTS: In the computational fluid dynamics model, the catheter with the 4-balloon array achieved the highest cooling rate of -1.6°C, which may be attributed to disruption of the thermal boundary layers. In the in vitro study, cooling of the blood substitute at flow rates of 400 mL/min (normal common carotid artery flow) and 250 mL/min (reduced common carotid artery flow due to distal MCA occlusion) achieved a temperature drop inside the blood substitute along the cooling balloons of -1.6°C and -2.2°C, respectively. CONCLUSIONS: The feasibility of intracarotid blood cooling using a new catheter system was demonstrated in vitro. A serial 4-balloon array led to an optimized cooling capacity approaching optimum target temperatures of mild therapeutic hypothermia. To determine the therapeutic efficacy of combined selective therapeutic hypothermia and mechanical thrombectomy, further in vivo studies by using a model of temporary ischemia with large-vessel occlusion and recanalization are required.

Hyperinsulinism in patients with coronary artery disease.

AIM: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization. METHODS: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD. RESULTS: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.45 microU/ml +/- 0.43 SEM; two-vessel disease: mean IRI 10.4 microU/ml +/- 0.71 SEM; three-vessel disease: mean IRI 11.88 microU/ml +/- 0.98 SEM) and inversely to the high-density lipoprotein level (P < 0.05). In patients with arterial hypertension, IRI levels were elevated, without a significant difference between those with and those without CAD, whereas the IRI levels of non-hypertensive men with CAD (n = 81; mean IRI 9.85 microU/ml +/- 0.51 SEM) differed significantly (P < 0.05) from those of non-hypertensive men without CAD (n = 59; mean IRI 7.76 microU/ml +/- 0.43 SEM). IRI levels were significantly higher (P < 0.05) in obese patients (n = 65; mean IRI 11.68 microU/ml +/- 0.70 SEM versus n = 203; mean IRI 9.32 microU/ml +/- 0.34 SEM), in patients with elevated triglycerides (n = 58 mean IRI 11.59 microU/ml +/- 0.81 SEM versus n = 210; mean IRI 9.42 microU/ml +/- 0.33 SEM), and in patients with lowered HDL cholesterol (n = 178; mean IRI 11.06 microU/ml +/- 0.63 SEM versus n = 90; mean IRI 9.29 microU/ml +/- 0.34 SEM). Diabetic patients on angiotensin converting enzyme inhibitor therapy (n = 11; mean IRI 7.91 microU/ml +/- 0.91 SEM) had significantly (P < 0.05) lower IRI levels than those not treated with ACE inhibitors (n = 25; mean IRI 12.96 microU/ml +/- 1.47 SEM). IRI levels exceeding 8 microU/ml were associated with a 1.98-fold risk for CAD compared with IRI levels below 8 microU/ml. Stepwise logistic regression showed that insulin was an independent determinant of CAD. CONCLUSION: Knowledge of the fasting insulin level is an important contribution to the identification of patients with, or at risk of, CAD.

[Interventional therapy after failed fibrinolysis in acute myocardial infarct. Acute and long-term outcome of referral for rescue balloon angioplasty]. / Interventionelle Therapie nach fehlgeschlagener Fibrinolyse beim akuten Myokardinfarkt. Akut- und Langzeitergebnisse nach Verlegung zur "Rescue"-Ballonangioplastie.

BACKGROUND: The results from studies of coronary angioplasty after failed thrombolysis (rescue-PTCA) in acute myocardial infarction are contradictory. Long-term results were not presented till now. Therefore we analyzed the data from our registry of those patients whose acute and long-term results were available. PATIENTS AND METHODS: Data of 49 patients were analyzed who had been admitted for rescue-PTCA from other hospitals. Thrombolysis had to be started < 6 hours (mean 2.7 hours) from onset of symptoms. Rescue-PTCA had to be completed within < 24 hours (mean 10.5 hours). 37 patients received streptokinase, seven rt-PA, three urokinase and two prourokinase. Electrocardiographic and clinical criteria were used to define failure of thrombolysis. The data of the acute results were from a prospective registry and the long-term results came from clinical follow-up visits and a questionnaire sent to the patients. RESULTS: Mean age of the patients was 48.5 years (38-78 years), 45 male, nine patients in cardiogenic shock (18%), infarct related artery (IRA): RCA 22x, LAD 21x, LCX 5x, CABG 1x, single vessel disease 27x, multiple vessel disease 22x. Acute results: Initial IRA-TIMI flow 0 in 28 patients, 1 in twelve patients, 2 in 9 patients; after rescue-PTCA TIMI flow 1 in one patient, 2 in two patients, 3 in 46 patients (procedural success 94%). Hospital mortality 8.2% (four patients), all in cardiogenic shock. Early reocclusion rate 10%. Bleeding complications 14%, no fatal complications. Long-term results: Observation period 2.5 years in 42 patients (0.5-6.5 years). Three more deaths. Total mortality 14% (7/49). Angiographic follow-up: Ejection fraction initially 50%; 53% after 3 months. Repeat revascularization in 43% (15/35): Re-PTCA in 8/35, surgery in 6/35 patients, 1x transplantation. 80% of the patients were free from angina or heart failure. CONCLUSIONS: Rescue-PTCA in acute myocardial infarction has a high procedural success rate with a low hospital mortality. It is the treatment of choice for patients in cardiogenic shock. Transportation to an interventional center is safe. The reintervention rate is comparably high. The long-term results are good.

Recanalisation of coronary chronic total occlusions with new techniques including the retrograde approach via collaterals.

OBJECTIVE: Percutaneous treatment of coronary chronic total occlusions (CTO) remains one of the major challenges in interventional cardiology. The strategies of recanalisation in CTO have changed drastically due the development of new techniques such as the retrograde approach via collaterals. In this single-centre experience we sought to analyse the success rates with the use of different CTO techniques, the complication rates, and we evaluated predictors of failed CTO recanalisation attempts. METHODS AND RESULTS: In this single-centre observational study we analysed the prospectively entered data of 331 consecutive patients, undergoing percutaneous coronary intervention (PCI) for CTO in 338 lesions at the Heart Center Wuppertal between June 2007 and July 2010. Nineteen lesions were attempted twice and one lesion three times (=358 procedures). The lesion-related success rates were 81.1%. Single-wire usage was the predominant strategy used in 198 antegrade cases (65.6%) followed by parallel wire technique and see-saw technique in 94 cases (31.1%). In the retrograde procedures, the reverse CART technique was predominantly used (35.7%), followed by retrograde wire passage (17.9%), marker wire (17.9%) and CART (14.3%). The in-hospital complications were low and comparable with conventional PCI data. The presence of blunt stump, severe calcification, severe tortuosity and occlusion length >30 mm were independent predictors of procedural failure. CONCLUSIONS: A high degree of success with low in-hospital complications comparable with conventional PCI data can be expected in the hands of experienced CTO operators. A second try with a retrograde approach after antegrade failure should be considered.

Newly detected glucose disturbance is associated with a high prevalence of diastolic dysfunction: double risk for the development of heart failure?

Diastolic dysfunction is associated with a high rate of morbidity and mortality and has a high prevalence in patients with diabetes. Aim of the study was to investigate the prevalence of diastolic dysfunction in patients with newly detected glucose metabolism disorder (GMD) submitted for coronary angiography. Oral glucose tolerance test, echocardiography, and tissue Doppler imaging were performed in patients referred to coronary angiography. Prevalence of diastolic dysfunction was 97, 88, and 74% in the known diabetes, newly detected diabetes, and new diagnosed impaired glucose tolerance group, respectively. This is higher than previously reported. Severity of diastolic dysfunction was associated with higher 2-h plasma glucose levels and with new diagnosed diabetes. Screening patients with newly detected GMD for diastolic dysfunction may identify patients with double risk for cardiovascular morbidity and mortality and this group might be a target population to avoid development heart failure.

Arbutamine stress echocardiography.

Arbutamine, a new potent non-selective beta-adrenoceptor agonist with mild alpha 1-sympathomimetic activity, has been developed specifically for pharmacological stress testing. The drug acts like physical exercise, increasing both heart rate and myocardial contractility. Sensitivity, specificity and accuracy in detecting significant stenotic coronary artery disease are 76%, 96%, and 82%, respectively, again similar to those of exercise echocardiography. The drug is delivered by a computerized drug delivery and monitoring device (GenESA) which adjusts the infusion rate according to the patient's heart rate data feedback. The drug is generally well tolerated and has an acceptable safety profile. This article describes recent clinical experience with arbutamine and presents preliminary results of a multicentre multinational study which evaluates the clinical utility and safety of the GenESA system in diagnosing coronary artery disease.

Stress echocardiography: personnel and technical equipment.

In recent years, stress echocardiography has gained broad acceptance as a non-invasive method for the diagnosis of coronary artery disease. Facing different protocols, dosages and instrumentation, official guidelines for the performance, standardization and quality control of stress echocardiograms are needed; however, so far they are not available. This paper recommends the type of personnel and technical equipment needed for stress echocardiography laboratories, based on experience gained during more than 2000 stress echocardiographic procedures. To perform stress echocardiography, a cardiologist and a technical assistant--both well trained over a large number of tests--should be involved. The laboratory must have basic equipment such as a 12-lead ECG, blood pressure monitoring capacity, a treadmill or bicycle for ergometry, a precision intravenous delivery system for pharmacological stress testing as well as an adequate echo table; additionally, emergency equipment is mandatory. The ultrasound machine should contain transducers with high 2-D resolution; most important is a digital image acquisition system which facilitates performance and interpretation through side-by-side display of synchronized rest and stress images. Finally, there is a need for proper patient preparation and the obtaining of informed consent.

Dobutamine stress echocardiography.

Dobutamine is a synthetic catecholamine with predominant beta-stimulation. Its half-life is approximately 2 min. The positive chronotropic and inotropic effects of dobutamine induce myocardial ischaemia if significant coronary artery obstruction is present. Regional ischaemia produces regional wall motion abnormalities which can be detected by echocardiography. Most dobutamine stress protocols start at an infusion rate of 5 micrograms.kg-1.min-1 and increase to a peak dose of 40 or 50 micrograms.kg-1.min-1; to further increase heart rate, a bolus injection of 0.25-1.0 mg atropine is added. Test endpoints are the detection of new wall motion abnormalities, the occurrence of severe complications or achievement of the target heart rate. Viable myocardial regions have a positive inotropic reserve, which can be stimulated by dobutamine and detected by echocardiography. Indications for the use of dobutamine stress echocardiography are to prove stress-inducible myocardial ischaemia and to detect myocardial viability. The test should only be performed for the detection of stress-induced myocardial ischaemia if patients are unable to undergo exercise echocardiography, or if patients fail to reach their required test level in exercise echocardiography.

Detection of myocardial viability using stress echocardiography.

Asynergic myocardial regions in patients with coronary artery disease can be viable. They may have the ability to improve their function after restoring coronary blood flow. Asynergic but viable myocardial regions have a positive inotropic reserve which can be stimulated by catecholamines. Because echocardiography is an established method for evaluating regional left ventricular function, it has the potential to detect the inotropic response of asynergic myocardial regions. In the clinical setting, prediction of left ventricular functional improvement after revascularization is particularly important. Dobutamine stress echocardiography is the most frequently used stress echocardiographic test for detection of myocardial viability. Dobutamine is infused at low rates of 2.5 to 20 micrograms.kg-1.min-1 to detect myocardial viability. This paper reports on the sensitivity and specificity of the method for the detection of viability and its usefulness for prediction of left ventricular functional improvement after revascularization.