Pre-operative risk factors for driveline infection in left ventricular-assist device patients.

AIMS: Implantation of left ventricular-assist devices (LVAD) to treat end-stage heart failure is of increasing relevance due to donor shortage. Infections of the driveline are common adverse events. LVAD infections can lead to high urgency listings for transplantation. However, transplantation in patients with infection leads to worse post-transplantation outcomes. This study aims to evaluate specific risk factors for driveline infections at the time of implantation. METHODS AND RESULTS: Four hundred forty-one patients receiving either Heartmate II or Heartware system from August 2009 to October 2013 were assessed. An expert committee sorted patients into four different groups concerning the likeliness of infection. Twenty-eight (6%) of discussed infection cases were judged as secured, 33 (7%) as likely, 18 (4%) as possible, and 20 (4%) as unlikely. The remaining 342 (78%) subjects showed either no signs of infection at all times (329 [75%]) or developed signs of infection in a second observation period within 1 year after ending of the first observation period (13 [3%]). For a better discriminatory power, cases of secured and likely infections were tested against the group with no infection at all times in a Cox proportional hazard model. Among all variables tested by univariate analysis (significance level P < 0.15), only age (P = 0.07), LVAD-type (P = 0.12), need for another thoracic operation (P = 0.02), and serum creatinine value (P = 0.02) reached statistical significance. These were subsequently subjected to multivariate analysis to calculate the cumulative risk of developing a drive infection. The multivariate analysis showed that of all the potential risk factors tested, only the necessity of re-thoracotomy or secondary thoracic closure had a significant, protective effect (hazard ratio [95% CI] = 0.45 [0.21-0.95]; P = 0.04). CONCLUSION: This single-centre cohort study shows that driveline infections are common adverse events. The duration of support represents the major risk factor for LVAD driveline infections.

18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus.

BACKGROUND: Bioprosthetic valve thrombosis may have implications for valve function and durability. OBJECTIVES: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves. METHODS: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT. RESULTS: Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake. CONCLUSIONS: Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875).

GMP-Compliant Radiosynthesis of [18F]GP1, a Novel PET Tracer for the Detection of Thrombi.

Thrombus formation and thromboembolic events play important roles in various cardiovascular pathologies. The key receptor involved in platelet aggregation is the fibrinogen receptor glycoprotein IIb/IIIa. [18F]GP1, a derivative of the GPIIb/IIIa antagonist elarofiban, is a specific 18F-labeled small-molecule radiotracer that binds with high affinity to GPIIb/IIIa receptors of activated platelets. An improved, robust and fully automated radiosynthesis of [18F]GP1 has been developed. [18F]GP1 has been synthesized with decay corrected radiochemical yields of 38 ± 6%, with a radiochemical concentration up to 1900 MBq/mL, molar activities of 952-9428 GBq/µmol and a radio-chemical purity >98%. After determination of the optimal reaction conditions, in particular for HPLC separation, adaption of the reaction conditions to PET center requirements, validation of the manufacturing process and the quality control methods, the synthesis of [18F]GP1 was successfully implemented to GMP standards and was available for clinical application. We describe the GMP-compliant synthesis of the novel radiotracer [18F]GP1. Moreover, we provide some proof-of-concept examples for clinical application in the cardiovascular field. PET/CT with the novel small-molecular radiotracer [18F]GP1 may serve as a novel highly sensitive tool for visualizing active platelet aggregation at the molecular level.

Myocardial perfusion after one year of spinal cord stimulation in patients with refractory angina.

AIM: Spinal cord stimulation (SCS) is recommended for patients with coronary artery disease (CAD) and refractory angina. We used positron emission tomography (PET) to investigate the long-term effect of SCS on regional myocardial perfusion in patients suffering from angina pectoris refractory to medical treatment and without option for coronary intervention. PATIENTS, METHODS: We analyzed data of 44 patients with stable CAD (91% three vessel disease). At baseline, we determined coronary flow reserve (CFR) using 13N-ammonia-PET and myocardial viability with 18F-FDG. SCS was performed for one year (Medtronic Itrell III or Synergy, Düsseldorf, Germany). During follow-up, no cardiac interventions were necessary and no myocardial infarctions occurred. At one year follow-up, CFR was measured again. RESULTS: In the majority of patients (77%), SCS led to an improvement of clinical symptoms. CFR did not change significantly during follow-up. Subjective improvement did not correlate with an increase of CFR. CONCLUSIONS: Despite its clinical effect, SCS does not have a direct impact on CFR in patients with stable CAD. According to our results, the pain relief is not due to an improvement of the myocardial blood supply.

Myocardial sympathetic innervation in patients with symptomatic coronary artery disease: follow-up after 1 year with neurostimulation.

UNLABELLED: In both diabetic and nondiabetic patients, there is a loose correlation between coronary flow reserve (CFR) and sympathetic innervation in viable myocardial segments. The loose correlation implies that sympathetic innervation may be preserved even with major impairment of myocardial blood supply. In some patients, denervation is due to repetitive episodes of ischemia in areas with severely reduced CFR. We investigated the long-term effect of reduced CFR on myocardial sympathetic innervation in diabetic and nondiabetic patients with spinal cord stimulation. METHODS: We analyzed 23 patients (10 diabetic and 13 nondiabetic) with coronary artery disease and without known cardiac autonomic neuropathy. At baseline, we determined quantitative myocardial blood flow using (13)N-ammonia PET, myocardial viability using (18)F-FDG PET, and cardiac innervation using (11)C-hydroxyephedrine (HED) PET. At the 1-y follow-up we measured CFR and (11)C-HED retention. During follow-up, no cardiac intervention was performed and no myocardial infarction occurred. In all patients, spinal cord stimulation was performed for relief of angina. RESULTS: There was no significant difference in segmental (11)C-HED retention between baseline and follow-up in the whole patient group. In diabetic patients, as well as in segments with severely reduced CFR (<1.5), (11)C-HED retention showed a small but significant decrease (P<0.05). Linear regression of segmental (11)C-HED retention between baseline and follow-up was high (r(2)=0.81), confirming good reproducibility of the investigation on the one hand and little change in regional sympathetic innervation on the other hand. CONCLUSION: In patients with stable chronic coronary artery disease, sympathetic innervation of the myocardium is almost unchanged in both diabetic and nondiabetic patients in a 1-y follow-up. In myocardial segments with severely altered blood supply, a small but significant decrease in (11)C-HED retention most probably reflects ischemic neuronal damage. The prognostic relevance of sympathetic denervation in viable myocardium still has to be determined.

Respiratory resistance of patients during cardiac stress testing with adenosine: is dyspnea a sign of bronchospasm?

BACKGROUND: Adenosine is widely used for stress-testing in myocardial perfusion imaging. During adenosine infusion, dyspnea is one of the main complaints of patients. The aim of this study was to determine whether dyspnea during adenosine infusion is caused by bronchospasm. METHODS: Fifty-four patients were enrolled in the study. Seven of these 54 suffered from mild chronic obstructive pulmonary disease (COPD). We continuously measured respiratory resistance (Rrs), using impulse oscillometry. Respiratory resistance was measured before, during, and after a continuous infusion of 140 microg/kg/min adenosine. RESULTS: Sixty-seven percent of patients suffered from dyspnea during adenosine infusion. In patients with mild COPD, Rrs was higher compared with other patients (0.48 vs 0.27 kPa/L/s, P < .05). Neither patients with COPD nor those without COPD exhibited a significant increase in Rrs during adenosine infusion. The Rrs of patients with dyspnea was insignificantly lower compared with patients without dyspnea (P = .469). CONCLUSIONS: Dyspnea as a side effect of adenosine infusion is not correlated with impaired respiratory resistance in nonasthmatic patients and in patients with mild COPD. Thus bronchospasm is ruled out as cause of this clinical symptom. Despite the small number of COPD patients enrolled in the study, adenosine infusion might be possible in patients with mild COPD.

Calcium distribution patterns of the aortic valve as a risk factor for the need of permanent pacemaker implantation after transcatheter aortic valve implantation.

AIMS: New-onset conduction disturbances still represent a considerable problem after transcatheter aortic valve implantation (TAVI). The aim of this study was to identify calcification patterns with an elevated risk for permanent pacemaker implantation (PPI) after TAVI and investigate underlying mechanisms in an ex vivo setting. METHODS AND RESULTS: One hundred and sixty-two patients who underwent TAVI with the Edwards SAPIEN XT® or Medtronic CoreValve® at our institution were analysed. The calcium load of the device landing zone was quantified with 3mensio®, and calcium patterns with an elevated risk for PPI were identified. Ex vivo simulations of balloon valvuloplasty were performed in 3D-printed silicone annuli of patients matching the identified risk profile. Patients with a calcium load of the left coronary cusp (LCC) above 209 mm3 had a higher rate of PPI than patients below this threshold (16.7 vs. 2.6%, P = 0.003). Multivariate regression revealed pre-existing right bundle branch block (RBBB) and increased LCC calcification as independent predictors for PPI. Simulation of the TAVI procedure in a silicone annulus revealed an off-centreline shift of the valvuloplasty balloon and transcatheter heart valve away from the LCC towards the commissure between right- and non-coronary cusp. CONCLUSION: Pre-existing RBBB and elevated LCC calcification were identified as independent predictors for PPI. These two risk factors enabled us to distinguish between patients according to their risk for PPI after TAVI. Ex vivo simulations suggested an off-centreline shift of the balloon as a possible explanation.

Non-invasive coronary angiography: the clinical value of multi-slice computed tomography in the assessment of patients with prior coronary bypass surgery. Evaluating grafts and native vessels.

BACKGROUND: Contrast enhanced multi-slice computed tomography (MSCT) is the leading modality in non-invasive coronary angiography (CTA) today. We investigated MSCT based assessment of coronary artery bypass grafts (CABG) by analyzing assets and drawbacks of CTA in order to define demands on latest technology. METHODS: In a clinical setting 39 CABG patients (69.2 +/- 1.4 years; male n = 36) underwent CTA (collimation 16 x 0.75 mm, contrast medium 100 ml; 320 mAs, 120 KV). Ninety-seven CABG (61 venous, 36 arterial grafts) were evaluated. A subgroup of 18 patients underwent additional invasive coronary angiography (CA). RESULTS: CTA for CABG assessment resulted in an overall sensitivity (sens.) of 100%, specificity (spec.) of 92.4% and positive and negative predictive values (PPV, NPV) of 60% and 100%, respectively. CABG anastomoses showed slightly inferior diagnostic accuracy than other CABG segments. Limitations in imaging quality caused 21% unevaluable segments of the CABG anastomoses. Evaluation of native vessel segments proximal and distal to the anastomoses resulted in a sens, spec, PPV and NPV of 57.5, 94.6, 92 and 67.3%, respectively. With 28.5% unevaluable segments, the native vessel segments showed serious limitations in imaging quality. Radiation exposure was 9.88 +/- 3.20 mSv (9.69 +/- 3.25 mSv male; 12.08 +/- 1.35 mSv female). CONCLUSION: 16-slice MSCT based CABG assessment offers sufficient diagnostic accuracy. However, focussing on the bypass anastomoses and the native revascularized coronary arteries, clinical value is limited.

Optimisation of protocol for low dose CT-derived attenuation correction in myocardial perfusion SPECT imaging.

PURPOSE: In clinical routine, attenuation correction (AC) using X-ray CT is a relatively new method for reducing attenuation artefacts. We evaluated the quality of attenuation maps generated with very low tube current to minimise exposure due to transmission scanning. METHODS: SPECT/CT acquisitions were performed with a Millenium VG3 gamma camera with the Hawkeye CT device (GE Medical Systems). In phantom studies, determination of linear absorption coefficients (mu) for air, water and Teflon was carried out. The attenuation maps in both stress and resting studies from 62 patients (21 females and 41 males, age 63.7 +/- 11.0 years, BMI 30.0 +/- 5.7 kg/m(2)) were compared. All patients underwent exercise or pharmacologic stress testing and a resting study for comparison using Tc-99m MIBI or Tc-99m Tetrofosmin. AC in stress studies was performed using 2.5 mA tube current (set as default), whereas 1.0 mA was used in resting studies. RESULTS: In both phantom and patient studies, differences of linear absorption coefficients were not significant (p > 0.05). Effective dose decreased from 0.90 mSv down to 0.36 mSv, respectively. CONCLUSION: Our results indicate that reliable attenuation maps (mu-maps) of the thorax can be obtained even with the use of very low tube current. In our study, radiation exposure in CT-based AC for myocardial perfusion SPECT was substantially lowered (60% reduction). This is of particular importance in high-risk patients who may have to undergo follow-up scans and in research studies on volunteers. The procedure introduced is relatively simple and can be transferred to other SPECT/CT devices, which allow adjustment of tube current.