Natriuretic Peptide Levels and Stages of Left Ventricular Dysfunction in Heart Failure with Preserved Ejection Fraction.

In heart failure with preserved ejection fraction (HFpEF), natriuretic peptide (NP) levels are frequently lower. In several trials, the outcome differed between patients with low and high NP levels. This suggests that NP could be used to identify distinct stages of left ventricular (LV) remodeling and myocardial tissue composition. This study investigated cardiac remodeling/dysfunction and myocardial tissue characteristics assessed by echocardiography and cardiac magnetic resonance (CMR) in HFpEF patients in relation to NP levels. Clinical and echocardiographic data of 152 HFpEF patients were derived from outpatient visits. A total of 71 HFpEF patients underwent CMR-derived T1-mapping. Multivariable regression analyses were performed to examine the association of NT-proBNP categories ( median) and NT-proBNP as continuous variable with echocardiography and CMR-derived T1-mapping. Mean age was 71 ± 9, 93% of patients were women and median NT-proBNP was 195 pg/mL, with 35% of patients below the diagnostic cut-off value (<125 pg/mL). Patients with high NT-proBNP had comparable LV systolic function and LV relaxation but significantly worse LV stiffness and left atrial function compared with patients with low NT-proBNP. Higher NT-proBNP was significantly associated with higher LV stiffness and extracellular volume fraction (ECV) (ß = 1.82, 95% CI: 0.19;3.44, p = 0.029). Higher NT-proBNP levels identify HFpEF patients with worse LV stiffness because of more severe myocardial extracellular matrix remodeling, representing an advanced stage of HFpEF.

The association between computed tomography angiography timing and workflow times in patients with acute ischemic stroke.

BACKGROUND: In most hospitals, computed tomography angiography (CTA) is nowadays routinely performed in patients with acute ischemic stroke. However, it is unclear whether CTA is best performed before or after start of intravenous thrombolysis (IVT), since acquisition of CTA before IVT may prolong door-to-needle times, while acquisition after IVT may prolong door-to-groin times in patients undergoing endovascular treatment. METHODS: We performed a before-versus-after study (CTA following IVT, period I and CTA prior to IVT, period II), consisting of two periods of one year each. This study is based on a prospective registry of consecutive patients treated with IVT in two collaborating high-volume stroke centers; one primary stroke center and one comprehensive stroke center. The primary outcome was door-to-needle times. Secondary outcomes included door-to-groin times. Quantile regression analyses were performed to evaluate the association between timing of CTA and workflow times, adjusted for prognostic factors. RESULTS: A total of 519 patients received IVT during the study period (246 in period I, 273 in period II). In the adjusted analysis, we found a nonsignificant 1.13 min median difference in door-to-needle times (95% confidence interval: 1.03-3.29). Door-to-groin times was significantly shorter in period II in both unadjusted and adjusted analysis with the latter showing a 19.16 min median difference (95% confidence interval: 3.08-35.24). CONCLUSIONS: CTA acquisition prior to start of IVT did not adversely affect door-to-needle times. However, a significantly shorter door-to-groin times was observed in endovascular treatment eligible patients. Performing CTA prior to start of IVT seems the preferred strategy.

Stratified Treatment of Heart Failure with preserved Ejection Fraction: rationale and design of the STADIA-HFpEF trial.

AIMS: High myocardial stiffness in heart failure with preserved ejection fraction (HFpEF) is attributed to comorbidity-induced structural and functional remodelling through inflammation and oxidative stress affecting coronary microvascular endothelial cells and cardiomyocytes, which augments interstitial fibrosis and cardiomyocyte stiffness. In murine and human HFpEF myocardium, sodium glucose co-transporter 2 (SGLT2) inhibition ameliorates cardiac microvascular endothelial cell and cardiomyocyte oxidative stress, while enhancing myocardial protein kinase G activity and lowering titin-based cardiomyocyte stiffness. Failure of previous HFpEF outcome trials refocuses attention to improving pathophysiological insight and trial design with better phenotyping of patients and matching of therapeutic targets to prevailing pathogenetic mechanisms. SGLT2 inhibition could represent a viable therapeutic option especially in HFpEF patients in whom high diastolic left ventricular (LV) stiffness is predominantly caused by elevated cardiomyocyte stiffness and associated endothelial dysfunction, whereas HFpEF patients with extensive myocardial fibrosis might be less responsive. This study aims to investigate a stratified treatment approach, using dapagliflozin in heart failure patients with preserved ejection fraction without evidence of significant myocardial fibrosis. METHODS AND RESULTS: The Stratified Treatment to Ameliorate DIAstolic left ventricular stiffness in early Heart Failure with preserved Ejection Fraction (STADIA-HFpEF) is a Phase II, randomized, 2 × 2 crossover trial, evaluating the efficacy of 13 weeks of treatment with dapagliflozin 10 mg od in 26 patients with HFpEF, with normal cardiac magnetic resonance imaging-derived extracellular volume. The co-primary endpoint is echocardiographically derived change in E/e'/LV end-diastolic volume index and change in mean LV e'. CONCLUSIONS: The STADIA-HFpEF trial will be the first study to evaluate the direct effects of dapagliflozin on amelioration of LV stiffness, using histological phenotyping to discern early HFpEF.

Minimal invasive aortic valve replacement: associations of radiological assessments with procedure complexity.

OBJECTIVES: Limited aortic annulus exposure during minimal invasive aortic valve replacement (mini-AVR) proves to be challenging and contributes to procedure complexity, resulting in longer procedure times. New innovations like sutureless valves have been introduced to reduce procedure complexity. Additionally, preoperative imaging could also contribute to reducing procedure times. Therefore, we hypothesize that Computed Tomography (CT)-image based measurements are associated with mini-AVR complexity. METHODS: One hundred patients who underwent a mini-sternotomy and had a preoperative CT scan were included. With a CT-based mini-AVR planning tool, we measured access distance, access angle, annulus dimensions, and calcium volume. The associations of these measurements with cardiopulmonary bypass (CPB) time and aortic cross-clamp (AoX) time were assessed using univariable and multivariable regression models. In the multivariable models, these measurements were adjusted for age and suture technique. RESULTS: In the univariable regression models, calcium volume and annulus dimensions were associated with longer CPB and AoX time. After adjusting for age and suture technique, increasing calcium volume was still associated with longer CPB (adjusted ß-coefficient 0.002, 95%-CI (0.005, 0.019), p-value = 0.002) and AoX time (adjusted ß-coefficient 0.010, 95%-CI (0.004, 0.016), p-value = 0.002). However, after adjusting for these confounders, the association between annulus dimensions and procedure times lost statistical significance. CONCLUSION: Increase in calcium volume are associated with longer CPB and AoX times, with age and sutureless valve implantation as independent confounders. In contrast to previous studies, access angle was not associated with procedure complexity.

CT measurement of changes in cerebral perfusion in patients with asymptomatic carotid artery stenosis undergoing carotid stenting prior to cardiac surgery: "proof of principle".

AIMS: To identify asymptomatic patients with impaired cerebral perfusion using CT perfusion (CTP) technique during staged carotid stenting (CAS) and cardiac surgery. METHODS AND RESULTS: This is a prospective, non-randomised study in 16 neurologically asymptomatic patients designed to analyse cerebral perfusion using CTP before and after CAS. Mean transit time (MTT) was significant lower and cerebral blood flow (CBF) was significantly higher in the non-target hemisphere compared to the target hemisphere before treatment (4.64 ± 1.08 s vs. 5.67 ± 1.29 and 57.37 ± 24.90 s vs. 48.19 ± 13.02, respectively). Mean dMTT (absolute difference in MTT values between treated and untreated hemisphere) decreased from 0.92 ± 1.08 s before to 0.04 ± 0.30 s after carotid revascularisation (p<0.05) and mean relative CBF (ratios of the treated to the untreated hemisphere) increased from 0.92 ± 0.12 to 1.04 ± 0.12 after revascularisation (p<0.05). Subgroup analysis based on pre-treatment dMTT showed significant changes in 50% of the patients with larger dMTT. There was one transient ischaemic attack reported 30 days after combined procedure. CONCLUSIONS: A significant improvement of cerebral perfusion after carotid stenting is shown in about 50% of the asymptomatic patients in this study. This suggests the potential presence of a compromised cerebral circulation in asymptomatic patients with severe carotid artery disease scheduled for cardiac surgery.

New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS).

BACKGROUND: The International Carotid Stenting Study (ICSS) of stenting and endarterectomy for symptomatic carotid stenosis found a higher incidence of stroke within 30 days of stenting compared with endarterectomy. We aimed to compare the rate of ischaemic brain injury detectable on MRI between the two groups. METHODS: Patients with recently symptomatic carotid artery stenosis enrolled in ICSS were randomly assigned in a 1:1 ratio to receive carotid artery stenting or endarterectomy. Of 50 centres in ICSS, seven took part in the MRI substudy. The protocol specified that MRI was done 1-7 days before treatment, 1-3 days after treatment (post-treatment scan), and 27-33 days after treatment. Scans were analysed by two or three investigators who were masked to treatment. The primary endpoint was the presence of at least one new ischaemic brain lesion on diffusion-weighted imaging (DWI) on the post-treatment scan. Analysis was per protocol. This is a substudy of a registered trial, ISRCTN 25337470. FINDINGS: 231 patients (124 in the stenting group and 107 in the endarterectomy group) had MRI before and after treatment. 62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new DWI lesion detected on post-treatment scans done a median of 1 day after treatment (adjusted odds ratio [OR] 5.21, 95% CI 2.78-9.79; p<0.0001). At 1 month, there were changes on fluid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5.93, 95% CI 2.25-15.62; p=0.0003). In patients treated at a centre with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12.20, 95% CI 4.53-32.84), whereas in those treated at a centre with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy group had new lesions on DWI (adjusted OR 2.70, 1.16-6.24; interaction p=0.019). INTERPRETATION: About three times more patients in the stenting group than in the endarterectomy group had new ischaemic lesions on DWI on post-treatment scans. The difference in clinical stroke risk in ICSS is therefore unlikely to have been caused by ascertainment bias. Protection devices did not seem to be effective in preventing cerebral ischaemia during stenting. DWI might serve as a surrogate outcome measure in future trials of carotid interventions. FUNDING: UK Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union, Netherlands Heart Foundation, and Mach-Gaensslen Foundation.

Grading of carotid artery stenosis with multidetector-row CT angiography: visual estimation or caliper measurements?

To assess the optimal method for grading carotid artery stenosis with computed tomographic angiography (CTA), we compared visual estimation to caliper measurements, and determined inter-observer variability and agreement relative to digital subtraction angiography (DSA). We included 46 patients with symptomatic carotid stenosis for whom CTA and DSA of 55 carotids was available. Stenosis quantification by CTA using visual estimation (CTA(VE)) (method 1) was compared with caliper measurements using subjectively optimized wide window settings (method 2) or predefined contrast-dependent narrow window settings (method 3). Measurements were independently performed by two radiologists and two residents. To determine accuracy and inter-observer variability, we calculated linear weighted kappa, performed a Bland-Altman analysis and calculated mean difference (bias) and standard deviation of differences (SDD). For inter-observer variability, kappa analysis was "very good" (0.85) for expert observers using CTA(VE) compared with "good" (0.61) for experts using DSA. Compared with DSA, method 1 led to overestimation (bias 5.8-8.0%, SDD 10.6-14.4), method 3 led to underestimation (bias -6.3 to -3.0%, SDD 13.0-18.1). Measurement variability between DSA and visual estimation on CTA (SDD 11.5) is close to the inter-observer variability of repeated measurements on DSA that we found in this study (SDD 11.6). For CTA of carotids, stenosis grading based on visual estimation provides better agreement to grading by DSA compared with stenosis grading based on caliper measurements.

Frequency and consequences of early in-stent lesions after carotid artery stent placement.

PURPOSE: To examine the prevalence of in-stent lesions 1 month after carotid artery stent placement with multidetector computed tomography (CT) angiography and to evaluate their possible causes and their consequences during 1-year follow-up. MATERIALS AND METHODS: Sixty-nine patients with symptomatic carotid artery stenosis underwent multidetector CT angiography of the carotid arteries 1 month after carotid artery stent placement. Patients were followed-up until 1 year after stent placement, when duplex ultrasonography (US) was performed. In-stent lesions were defined as hypo- or hyperattenuating lesions at the stent wall found with multidetector CT. Significant restenosis (70%) at 1 year was defined as a peak systolic velocity of more than 300 cm/sec at duplex US. The Fisher exact test was used to assess the relationship between early in-stent lesions and ischemic events and restenosis. RESULTS: At 1 month, 14 of the 69 patients (20%) were found to have in-stent lesions. In one patient, the stent was occluded. The other 13 in-stent lesions did not result in significant lumen reduction. In the year following stent placement, no difference in ischemic events was found between patients with (14%) and those without (13%) early in-stent lesions (P = .99). There was no difference in the occurrence of restenosis at 1 year (7% vs 4%, P = .59). CONCLUSIONS: At 1 month after carotid artery stent placement, in-stent lesions are found in about one-fifth of patients. These lesions do not appear to be related to recurrent ischemic events or to restenosis at 1 year.

Changes in cerebral perfusion after revascularization of symptomatic carotid artery stenosis: CT measurement.

PURPOSE: To prospectively evaluate changes in brain perfusion computed tomographic (CT) parameters after revascularization of unilateral symptomatic carotid artery stenosis and to determine whether pretreatment perfusion CT parameters can be used to predict changes in cerebral hemodynamics after treatment. MATERIALS AND METHODS: This study was medical ethics committee approved, and written informed consent was obtained from all patients. Thirty-six patients (23 men, 13 women; mean age, 67 years) with unilateral symptomatic carotid artery stenosis underwent multi-detector row perfusion CT before and after revascularization. Mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were calculated, and relative values based on the comparison between symptomatic and asymptomatic hemispheres-specifically, relative CBV, relative CBF, and difference in MTT-were derived. The absolute and relative perfusion values before treatment were assessed and compared with posttreatment values. These analyses were performed for the group as a whole by using the t test and after subdividing patients into three tertiles according to the difference in MTT by using the Wilcoxon signed rank test. RESULTS: Among the absolute perfusion values, only the MTT in the symptomatic hemisphere improved significantly after treatment (P < .01). All relative values (difference in MTT, relative CBV, and relative CBF) changed significantly after treatment (P < .05). When the patients were subdivided into three tertiles according to difference in MTT, no significant change in any relative perfusion value could be demonstrated in the lowest tertile, only the difference in MTT improved significantly (P = .004) in the middle tertile, and all relative perfusion values changed significantly (P = .002) in the highest tertile. CONCLUSION: Compared with relative CT perfusion values based on interhemispheric comparison, absolute perfusion CT values are less suited for demonstrating changes in cerebral perfusion after revascularization in patients with unilateral symptomatic carotid artery stenosis.

Circle of Willis at CT angiography: dose reduction and image quality--reducing tube voltage and increasing tube current settings.

PURPOSE: To prospectively assess the effects of lower tube voltage and various effective tube currents on image quality for computed tomographic (CT) angiography of the circle of Willis. MATERIALS AND METHODS: Institutional review board approval was obtained. Patients or family provided written informed consent. Signal-to-noise ratios (SNRs) were determined in a head phantom for various effective tube currents with tube voltages of 90, 120, and 140 kVp. Patients were referred for CT angiography because of acute subarachnoid hemorrhage (n = 20) or family history of cerebral aneurysms (n = 20). In each group, 10 patients were scanned with 120 kVp and 200 mAs(eff) and 10 were scanned with 90 kVp and 330 mAs(eff) (CT dose index volumes, 27.2 mGy and 20.6 mGy, respectively). CT numbers were measured in the internal carotid artery at the T junction and compared with a t test. Two radiologists used a five-point scale to subjectively score arterial enhancement, depiction of small arterial detail, image noise, venous contamination, and interference of subarachnoid blood. Mann-Whitney U test was used for statistical analysis. RESULTS: In the phantom, SNR(2) was proportional to effective tube current and CT dose index volume. With an identical effective tube current, SNR(2) was lower at 90 kVp than at 120 or 140 kVp. With identical CT dose index volume, tube voltage of 90 kVp resulted in a 45%-52% increase of SNR(2) compared with SNR(2) at 120 kVp. In patients, mean attenuation in the internal carotid artery T junction was higher with 90 kVp (340 HU) than with 120 kVp (252 HU, P < .001). Although dose at 90 kVp was 30% lower than dose at 120 kVp, scores for arterial enhancement and depiction of small arterial detail were higher at 90 kVp than at 120 kVp (4.0 vs 3.2 and 3.6 vs 3.1, respectively; P < .005). CONCLUSION: In head phantoms, lower tube voltage improved SNR at equal radiation doses. For CT angiography of the circle of Willis, this translated into superior image quality at 90 kVp.

Perfusion-CT assessment of infarct core and penumbra: receiver operating characteristic curve analysis in 130 patients suspected of acute hemispheric stroke.

BACKGROUND AND PURPOSE: Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra. METHODS: One hundred and thirty patients with symptoms suggesting hemispheric stroke < or =12 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard. RESULTS: The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of 145%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 ml x 100 g(-1). CONCLUSIONS: In a large series of 130 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

Size and complexity of social networks among substance abusers: childhood and current correlates.

The objective of this study was to identify parental, childhood, demographic, and social function factors associated with social network size and complexity among substance abusers using retrospective data regarding family and childhood history and current data regarding demographic characteristics and psychosocial function. The authors interviewed 505 voluntary patients with substance abuse at two university medical centers in Minnesota and Oklahoma with alcohol-drug programs located within departments of psychiatry. Data collection instruments included a childhood questionnaire, a demographic checklist, and two psychiatric rating scales of psychosocial function. The authors found that years of education, current residence with others, being actively occupied at work or school, and higher psychosocial function on two psychiatrist-rated scales were associated with increased social network size and complexity. Loss of mother, out-of-home placement, and runaway before age 18 were associated with smaller social networks in adulthood. Age, gender, and current marital status were not associated with social network. Regression analysis indicated that network size (i.e., the number of individuals in the network) was associated with higher psychosocial function over the last year but not over the last two weeks, whereas network complexity (ie, the number of subgroups in the network) was related to psychosocial function over both the last year and the last two weeks. These data indicate that in addicted persons, both childhood factors and current social factors affect network size and complexity. Network complexity may be amenable to short-term change, whereas network size may be more related to longer-term coping.

Waiting times for radiotherapy: consequences of volume increase for the TCP in oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: Waiting lists for radiotherapy have become longer over the past years. Apart from the psychological distress for the patient we are concerned about tumour growth during this waiting time, which may worsen prognosis. The purpose of this pilot study was to investigate tumour growth in the waiting time and to obtain an indication of its clinical consequences for patients with oropharyngeal carcinoma. A tumour control probability (TCP) model was applied to evaluate consequences for outcome. METHODS AND MATERIALS: Increase in tumour volume was measured for 13 patients with oropharyngeal carcinoma by outlining the tumour on the diagnostic as well as on the treatment planning CT scan. Waiting time was defined as time between histopathological diagnosis and start of radiotherapy. For each tumour we calculated the increase in tumour volume and the tumour doubling time. The potential increase in TCP was calculated for each tumour for the situation without treatment delay. RESULTS: The mean increase in tumour volume was 70%. The mean waiting time was 56 days. Expected TCP with incorporation of delay was 47%, without delay it might have been 63-66%. CONCLUSION: This study shows tumour progression during the time between the diagnostic CT scan and the treatment planning CT scan in oropharyngeal cancer. As a consequence of waiting time, which allows tumour volume increase, there may be an average control loss of 16-19 % for these tumours during the total waiting time before radiotherapy.