Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

Timing-Invariant CT Angiography Derived from CT Perfusion Imaging in Acute Stroke: A Diagnostic Performance Study.

BACKGROUND AND PURPOSE: Timing-invariant (or delay-insensitive) CT angiography derived from CT perfusion data may obviate a separate cranial CTA in acute stroke, thus enhancing patient safety by reducing total examination time, radiation dose, and volume of contrast material. We assessed the diagnostic accuracy of timing-invariant CTA for detecting intracranial artery occlusion in acute ischemic stroke, to examine whether standard CTA can be omitted. MATERIALS AND METHODS: Patients with suspected ischemic stroke were prospectively enrolled and underwent CTA and CTP imaging at admission. Timing-invariant CTA was derived from the CTP data. Five neuroradiologic observers assessed all images for the presence and location of intracranial artery occlusion in a blinded and randomized manner. Sensitivity and specificity of timing-invariant CTA and standard CTA were calculated by using an independent expert panel as the reference standard. Interrater agreement was determined by using κ statistics. RESULTS: We included 108 patients with 47 vessel occlusions. Overall, standard CTA and timing-invariant CTA provided similar high diagnostic accuracy for occlusion detection with a sensitivity of 96% (95% CI, 90%-100%) and a specificity of 100% (99%-100%) for standard CTA and a sensitivity of 98% (95% CI, 94%-100%) and a specificity of 100% (95% CI, 100%-100%) for timing-invariant CTA. For proximal large-vessel occlusions, defined as occlusions of the ICA, basilar artery, and M1, the sensitivity and specificity were 100% (95% CI, 100%-100%) for both techniques. Interrater agreement was good for both techniques (mean κ value, 0.75 and 0.76). CONCLUSIONS: Timing-invariant CTA derived from CTP data provides diagnostic accuracy similar to that of standard CTA for the detection of artery occlusions in acute stroke.

Technical and Clinical Success and Long-Term Durability of Endovascular Treatment for Atherosclerotic Aortic Arch Branch Origin Obstruction: Evaluation of 144 Procedures.

OBJECTIVES: Endovascular treatment of atherosclerotic obstruction of aortic arch branch origins (AABO) has largely replaced open surgery, but long-term outcome data are lacking. This study evaluated mid-term and long-term results of these procedures. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Patients underwent endovascular treatment for symptomatic atherosclerotic stenosis of AABO between 1995 and 2012. Technical success was defined as uncomplicated revascularization and residual stenosis ≤30%. The primary end point was freedom from restenosis ≥50% on Duplex ultrasonography or magnetic resonance angiography. Secondary end points were freedom from target lesion revascularization or recurrent symptoms. RESULTS: 144 lesions were treated in 114 patients (75 female; mean age 66.3 years), by percutaneous transluminal angioplasty (PTA) in 20 patients and PTA and stent in 117 patients (brachiocephalic artery [BCA] 9/54; left common carotid artery [LCCA] 0/7; left subclavian artery [LSA] 11/56). The lesion could not be passed in four patients, and in three patients the intervention was terminated before angioplasty. The 30-day technical success was 94.4%, without deaths or strokes. Mean follow-up was 52.0 months (range 2-163 months). Restenosis-free survival was 95.6%, 92.9%, 87.6%, and 83.2% at 12, 24, 48, and 60 months, respectively. Log-rank test showed no significant difference between PTA only and PTA with additional stent placement at any point (p = .375), nor between BCA (n = 51), LCCA (n = 6), or LSA (n = 57). During follow-up, 27 patients (23.7%) became symptomatic (15 BCA, 1 LCCA, and 11 LSA); 19 patients with a restenosis of the target lesion (mean 56.7 months). Symptom-free survival was 94.7%, 92.0%, 82.3%, and 77.9% at 12, 24, 48, and 60 months, respectively. CONCLUSION: Endovascular treatment of aortic arch branch origin obstruction is safe and efficacious in experienced hands and can be considered as the preferred treatment, with good mid-term durability. Recurrent symptomatic lesions can be treated safely by renewed endovascular means.

Catheter-directed thrombolysis for acute upper extremity ischemia.

AIM: Acute nontraumatic upper extremity ischemia has significant chronic disability when not treated adequately and timely. As surgical treatment can be challenging, this study evaluates catheter-directed thrombolysis as first-line treatment for acute upper extremity ischemia. METHODS: Between January 2006 and December 2010, 28 patients (22 women; mean age, 63±16 years) underwent catheter-directed thrombolysis for acute upper extremity ischemia, Rutherford class I or IIa. Proximal extent of the occlusion was in the subclavian (32%), axillary (7%), brachial (25%) and forearm arteries (36%). Median occlusion length was 18 cm (range, 12-43). Causes were embolus (14%), thrombus (39%), thoracic outlet syndrome (14%), paraneoplastic (4%), or unknown (29%). RESULTS: Technical success was 96%, radiologic success (>95% clot lysis) 61%, and clinical success 68%. Median duration of thrombolysis was 24 hours (range, 18-96). Of the 11 radiologically unsuccessful patients (39%), five were treated conservatively and six underwent surgical intervention. In-hospital amputation-rate was 7%. Four complications occurred: embolization to the lower extremity, a transient ischemic attack, a subcapsular splenic hematoma and a pseudoaneurysm. Cumulative amputation-free survival at six months was 93%, standard error (SE) 4.87 and at one year 88%, SE 6.50. CONCLUSION: These results show that catheter-directed thrombolysis is effective in over 60% of patients as first-line treatment of extensive acute upper extremity ischemia and can prevent surgical intervention in these patients.

CT attenuation measurements are valuable to discriminate pledgets used in prosthetic heart valve implantation from paravalvular leakage.

OBJECTIVES: Sutures with polytetrafluorethylene (PTFE) felt pledgets are commonly used in prosthetic heart valve (PHV) implantation. Paravalvular leakage can be difficult to distinguish from PTFE felt pledgets on multislice CT because both present as hyperdense structures. We assessed whether pledgets can be discriminated from contrast-enhanced solutions (blood/saline) on CT images based on attenuation difference in an ex vivo experiment and under in vivo conditions. METHODS: PTFE felt pledgets were sutured to the suture ring of a mechanical PHV and porcine aortic annulus, and immersed and scanned in four different contrast-enhanced (Ultravist®; 300 mg jopromide ml(-1)) saline concentrations (10.0, 12.0, 13.6 and 15.0 mg ml(-1)). Scanning was performed on a 256-slice scanner with eight different scan protocols with various tube voltage (100 kV, 120 kV) and tube current (400 mAs, 600 mAs, 800 mAs, 1000 mAs) settings. Attenuation of the pledgets and surrounding contrast-enhanced saline were measured. Additionally, the attenuation of pledgets and contrast-enhanced blood was measured on electrocardiography (ECG)-gated CTA scans of 19 patients with 22 PHVs. RESULTS: Ex vivo CT attenuation differences between the pledgets and contrast-enhanced solutions were larger by using higher tube voltages. CT attenuation values of the pledgets were higher than contrast-enhanced blood in patients: 420±26 Hounsfield units (mean±SD, range 383-494) and 288±41 Hounsfield units (range 202-367), respectively. CONCLUSIONS: PTFE felt pledgets have consistently higher attenuation than surrounding contrast-enhanced blood. CT attenuation measurements therefore may help to differentiate pledgets from paravalvular leakage, and detect paravalvular leakage in patients with suspected PHV dysfunction.

Evaluation of a multi-atlas based method for segmentation of cardiac CTA data: a large-scale, multicenter, and multivendor study.

PURPOSE: Computed tomography angiography (CTA) is increasingly used for the diagnosis of coronary artery disease (CAD). However, CTA is not commonly used for the assessment of ventricular and atrial function, although functional information extracted from CTA data is expected to improve the diagnostic value of the examination. In clinical practice, the extraction of ventricular and atrial functional information, such as stroke volume and ejection fraction, requires accurate delineation of cardiac chambers. In this paper, we investigated the accuracy and robustness of cardiac chamber delineation using a multiatlas based segmentation method on multicenter and multivendor CTA data. METHODS: A fully automatic multiatlas based method for segmenting the whole heart (i.e., the outer surface of the pericardium) and cardiac chambers from CTA data is presented and evaluated. In the segmentation approach, eight atlas images are registered to a new patient's CTA scan. The eight corresponding manually labeled images are then propagated and combined using a per voxel majority voting procedure, to obtain a cardiac segmentation. RESULTS: The method was evaluated on a multicenter/multivendor database, consisting of (1) a set of 1380 Siemens scans from 795 patients and (2) a set of 60 multivendor scans (Siemens, Philips, and GE) from different patients, acquired in six different institutions worldwide. A leave-one-out 3D quantitative validation was carried out on the eight atlas images; we obtained a mean surface-to-surface error of 0.94 +/- 1.12 mm and an average Dice coefficient of 0.93 was achieved. A 2D quantitative evaluation was performed on the 60 multivendor data sets. Here, we observed a mean surface-to-surface error of 1.26 +/- 1.25 mm and an average Dice coefficient of 0.91 was achieved. In addition to this quantitative evaluation, a large-scale 2D and 3D qualitative evaluation was performed on 1380 and 140 images, respectively. Experts evaluated that 49% of the 1380 images were very accurately segmented (below 1 mm error) and that 29% were accurately segmented (error between 1 and 3 mm), which demonstrates the robustness of the presented method. CONCLUSIONS: A fully automatic method for whole heart and cardiac chamber segmentation was presented and evaluated using multicenter/multivendor CTA data. The accuracy and robustness of the method were demonstrated by successfully applying the method to 1420 multicenter/ multivendor data sets.

Unrecognised myocardial infarction in subjects at high vascular risk: prevalence and determinants.

OBJECTIVE: To investigate the prevalence and determinants of unrecognised myocardial infarction (UMI). DESIGN, SETTING, PATIENTS: In this cross-sectional study in a tertiary centre, a delayed enhancement cardiac MRI (DE-CMR), which identifies both Q-wave and non-Q wave MIs, was performed in 502 subjects with manifest extracardiac atherosclerotic disease or marked risk factors for atherosclerosis without symptomatic coronary artery disease. MAIN OUTCOME MEASURES: UMI was defined as the presence of delayed enhancement without corresponding clinical history. RESULTS: DE-CMR was of sufficient image quality in 480 (95.6%) subjects. A UMI was present in 45 (9.4%) of all subjects; in 13.1% of men and in 3.7% of women. The risk of UMI increased from 6.0% (95% CI 2.2 to 9.8%) in those with two vascular risk factors up to 26.2% (95% CI 15.2 to 37.3%) in those with four or five risk factors. In a multivariable analysis, the risk of UMI was related to male gender (OR 2.3 (95% CI 1.0 to 5.6)), age (OR 1.04 (95% CI 1.00 to 1.07) per year), ever smoking (OR 3.1 (95% CI 1.0 to 9.1), history of stroke (OR 1.9 (95% CI 0.8 to 4.3)) and history of aneurysm of the abdominal aorta (OR 2.6 (95% CI 1.0 to 6.9)). CONCLUSIONS: In cardiac asymptomatic subjects at high vascular risk, UMI is common. The risk of UMI increases with increasing presence of risk factors.

Rationale and design of the SMART Heart study: A prediction model for left ventricular hypertrophy in hypertension.

Left ventricular hypertrophy (LVH) is an independent risk factor for the development of heart failure, coronary heart disease and stroke. LVH develops in response to haemodynamic overload, e.g. hypertension. LVH was originally thought to start as an adaptive and beneficial response required to normalise wall stress. However, this concept has been challenged by recent animal experiments suggesting that any degree of LVH is detrimental for the preservation of cardiac function and survival. If confirmed in humans, these findings imply that an increase in LV mass should be prevented, e.g. by lifestyle or pharmacological interventions. To facilitate and optimise interventions, the SMART Heart study was recently set up to develop a prediction model, also involving single nucleotide polymorphism data, for the identification of subjects at high risk of developing LVH in hypertension. For this purpose 1000 subjects with chronic hypertension will undergo cardiac MR imaging. In addition, this study allows the extrapolation of animal experimental genetic research into the human situation. (Neth Heart J 2007;15:295-8.).

Influence of partial volume on venous output and arterial input function.

BACKGROUND: CT perfusion (CTP) is an important diagnostic tool for the imaging of cerebral hemodynamics. To obtain quantitative values of cerebral blood volume (CBV), blood flow (CBF), and mean transit time (MTT), measurement of the arterial input function (AIF) is required. To correct for partial volume effects (PVEs), it is common to normalize the AIF with respect to the venous output function (VOF). This correction assumes that measurement of the VOF is unhampered by PVEs. The purpose of this study was to evaluate the effect of PVE on the measurement of the AIF and VOF and, consequently, on the absolute perfusion parameters. METHODS: In 10 patients the mean area under the curve (AUC) of the AIF and VOF were quantified for 3-, 6-, and 12-mm-thick sections. Differences in the mean (1) AUC of the VOF, (2) AUC of the AIF, and (3) width of the AIF were compared for the 3 section thicknesses, and the influence on the absolute values of CBV, CBF, and MTT were studied. RESULTS: With thinner sections, the AUC of the VOF and the AIF increased significantly and the width of the AIF decreased slightly. Differences in AUC between the 3 section thicknesses were larger for the AIF than for the VOF. CONCLUSION: PVEs affect not only the AIF, but also the VOF. This results in an overestimation of CBV and CBF when a thicker section is used. To avoid PVE, VOF measurements should be performed at lower section thicknesses.

Novel ways to noninvasively detect inflammation of the myocardium: contrast-enhanced MRI and myocardial contrast echocardiography.

Both contrast-enhanced magnetic resonance imaging (CE-MRI) and myocardial contrast echocardiography (MCE) are promising tools to detect cardiac inflammation. CE-MRI can be used to characterise the location and extent of myocardial inflammation, since areas of abnormal signal enhancement associated with regional wall motion abnormalities reliably indicate areas of active myocarditis. In MCE, chemically composed microbubbles can be visualised by ultrasound and used to determine the status of the cardiac microvasculature. If there is any inflammation the microbubbles will be phagocytosed by neutrophils and monocytes, thus enabling the degree of inflammation to be assessed. These noninvasive techniques may allow early diagnosis and accurate evaluation of myocardial inflammation.

Measurement of cerebral perfusion with dual-echo multi-slice quantitative dynamic susceptibility contrast MRI.

Quantitative cerebral perfusion was measured in vivo using dynamic susceptibility contrast magnetic resonance imaging. A dual-echo acquisition was used to eliminate T(1)-enhancement. The arterial input curve was measured in a separate slice in the neck to minimize partial volume effects. Data analysis was performed using a maximum likelihood expectation maximization method to be less sensitive to noise or contrast arrival time differences. From the contrast response curves obtained, the cerebral blood volume (CBV) and flow (CBF) and the timing parameters mean transit time (MTT), time of appearance (TA), and time-to-bolus peak (TBP) were obtained. Adjacent slices were measured to permit discrimination between intra- and inter-subject variance. The group investigated consisted of 41 subjects without cerebral pathology on anatomical MRI. Perfusion parameters for gray (GM) and white matter (WM) were obtained: CBV (GM) = 6.78 +/- 0.99 ml/100 ml, CBV (WM) = 3.78 +/- 0. 96 ml/100 ml, CBF (GM) = 68.7 +/- 21.2 ml/100 ml/min, CBF (WM) = 35. 8 +/- 12.7 ml/100 ml/min, and average GM/WM ratio for CBV (GM/WM) = 1.87 +/- 0.42 and CBF (GM/WM) = 1.99 +/- 0.48. Measured temporal aspects of perfusion were: mean transit time (MTT) (GM) = 6.4 +/- 1. 8 seconds, MTT (WM) = 6.9 +/- 2.3 seconds, time of appearance (TA) (GM) = 1.4 +/- 0.9 seconds, TA (WM) = 2.0 +/- 1.0 seconds, and time-to-bolus peak (TBP) (GM) = 2.4 +/- 1.4 seconds, TBP (WM) = 3.0 +/- 1.5 seconds. The average values were in agreement with those from the literature. Inter- and intra-person variances were estimated using an ANOVA test, and the sources of variance in the parameters, such as image noise, biological variability, and measurement errors of the arterial input curve were found to be of the same order of magnitude. J. Magn. Reson. Imaging 1999;10:109-117.