Pulmonary Vein Isolation for Atrial Fibrillation: Comparison of a Very High-Power Very Short-Duration (vHPvSD) Ablation Protocol versus a Hybrid Ablation Approach-Procedural and Mid-Term Outcome Data.

Background: Pulmonary vein isolation (PVI) using radiofrequency ablation (RFA) is a standard-of-care treatment in the rhythm control strategy of symptomatic atrial fibrillation (AF). Ablation protocols, varying in the power and duration of energy delivery, have changed rapidly in recent years. Very high-power very short-duration ablation (vHPvSD) is expected to shorten procedural times compared to conventional ablation approaches. However, the existing data suggest that this might come at the cost of lower first-pass isolation rates, a predictor of poor ablation long-term outcomes. This study aims to compare a vHPvSD protocol to a hybrid strategy, in which the power and duration of the energy transfer are adapted depending on the anatomical location. Methods: We retrospectively analyzed procedural and outcome data from 93 patients (55 vHPvSD vs. 38 hybrid) scheduled for de novo pulmonary vein isolation. A vHPvSD ablation protocol (90 Watt (W), 4 s) was compared to a hybrid protocol using vHPvSD on the posterior wall and 50 W HPSD (high-power short-duration) ablation guided by the Ablation Index along the remaining spots. Results: Ablation times were significantly shorter in the vHPvSD cohort (5.4 min. vs. 14.2 min, p < 0.001), thus resulting in a significant reduction in the overall procedural duration (91 min vs. 106 min, p = 0.003). The non-significant slightly higher first-pass isolation rates in the vHPvSD cohort (85% vs. 76%, p = 0.262) did not affect freedom from AF 6 months after the procedure (83% vs. 87%, p = 0.622). Conclusions: vHPvSD helps in shortening the PVI procedural duration, thus neither affecting first-pass isolation rates nor freedom from atrial tachyarrhythmia recurrence at 6 months after the index procedure.

New Frontiers in Electrocardiography, Cardiac Arrhythmias, and Arrhythmogenic Disorders.

In recent decades, diagnosing, risk-stratifying, and treating patients with primary electrical diseases, as well as heart rhythm disorders, have improved substantially [...].

Single-cell analysis of MYD88L265P and MYD88WT Waldenström macroglobulinemia patients.

Waldenström macroglobulinemia (WM) is characterized by the expansion of clonal lymphoplasmacytic cells; the MYD88L265P somatic mutation is found in >90% of patients, but malignant B cells may still display intra-clonal heterogeneity. To assess clonal heterogeneity in WM, we generated and performed single-cell RNA sequencing of CD19+ sorted cells from five patients with MYD88 L265P and two patients with MYD88 WT genotype as well as two healthy donors. We identified distinct transcriptional patterns in the clonal subpopulations not only between the two genetically distinct WM subgroups but also among MYD88 L265P patients, which affected the B cell composition in the different subgroups. Comparison of clonal and normal/polyclonal B cells within each patient sample enabled the identification of patient-specific transcriptional changes. We identified gene signatures active in a subset of MYD88L265P patients, while other signatures were active in MYD88 WT patients. Finally, gene expression analysis showed common transcriptional features between patients compared to the healthy control but also differentially expressed genes between MYD88 L265P and MYD88 WT patients involved in distinct pathways, including NFκΒ, BCL2, and BTK. Overall, our data highlight the intra-tumor clonal heterogeneity in WM with potential prognostic and therapeutic implications.

Silent cerebral lesions following catheter ablation for atrial fibrillation: a state-of-the-art review.

Atrial fibrillation is associated with neurocognitive comorbidities such as stroke and dementia. Evidence suggests that rhythm control-especially if implemented early-may reduce the risk of cognitive decline. Catheter ablation is highly efficacious for restoring sinus rhythm in the setting of atrial fibrillation; however, ablation within the left atrium has been shown to result in MRI-detected silent cerebral lesions. In this state-of-the-art review article, we discuss the balance of risk between left atrial ablation and rhythm control. We highlight suggestions to lower the risk, as well as the evidence behind newer forms of ablation such as very high power short duration radiofrequency ablation and pulsed field ablation.

Geometric distortion assessment in 3T MR images used for treatment planning in cranial Stereotactic Radiosurgery and Radiotherapy.

Magnetic Resonance images (MRIs) are employed in brain Stereotactic Radiosurgery and Radiotherapy (SRS/SRT) for target and/or critical organ localization and delineation. However, MRIs are inherently distorted, which also impacts the accuracy of the Magnetic Resonance Imaging/Computed Tomography (MRI/CT) co-registration process. In this phantom-based study, geometric distortion is assessed in 3T T2-weighted images (T2WIs), while the efficacy of an MRI distortion correction technique is also evaluated. A homogeneous polymer gel-filled phantom was CT-imaged before being irradiated with 26 4-mm Gamma Knife shots at predefined locations (reference control points). The irradiated phantom was MRI-scanned at 3T, implementing a T2-weighted protocol suitable for SRS/SRT treatment planning. The centers of mass of all shots were identified in the 3D image space by implementing an iterative localization algorithm and served as the evaluated control points for MRI distortion detection. MRIs and CT images were spatially co-registered using a mutual information algorithm. The inverse transformation matrix was applied to the reference control points and compared with the corresponding MRI-identified ones to evaluate the overall spatial accuracy of the MRI/CT dataset. The mean image distortion correction technique was implemented, and resulting MRI-corrected control points were compared against the corresponding reference ones. For the scanning parameters used, increased MRI distortion (>1mm) was detected at areas distant from the MRI isocenter (>5cm), while median radial distortion was 0.76mm. Detected offsets were slightly higher for the MRI/CT dataset (0.92mm median distortion). The mean image distortion correction improves geometric accuracy, but residual distortion cannot be considered negligible (0.51mm median distortion). For all three datasets studied, a statistically significant positive correlation between detected spatial offsets and their distance from the MRI isocenter was revealed. This work contributes towards the wider adoption of 3T imaging in SRS/SRT treatment planning. The presented methodology can be employed in commissioning and quality assurance programmes of corresponding treatment workflows.

Target localization accuracy in frame-based stereotactic radiosurgery: Comparison between MR-only and MR/CT co-registration approaches.

PURPOSE: In frame-based Gamma Knife (GK) stereotactic radiosurgery two treatment planning workflows are commonly employed; one based solely on magnetic resonance (MR) images and the other based on magnetic resonance/computed tomography (MR/CT) co-registered images. In both workflows, target localization accuracy (TLA) can be deteriorated due to MR-related geometric distortions and/or MR/CT co-registration uncertainties. In this study, the overall TLA following both clinical workflows is evaluated for cases of multiple brain metastases. METHODS: A polymer gel-filled head phantom, having the Leksell stereotactic headframe attached, was CT-imaged and irradiated by a GK Perfexion unit. A total of 26 4-mm shots were delivered at 26 locations directly defined in the Leksell stereotactic space (LSS), inducing adequate contrast in corresponding T2-weighted (T2w) MR images. Prescribed shot coordinates served as reference locations. An additional MR scan was acquired to implement the "mean image" distortion correction technique. The TLA for each workflow was assessed by comparing the radiation-induced target locations, identified in MR images, with corresponding reference locations. Using T1w MR and CT images of 15 patients (totaling 81 lesions), TLA in clinical cases was similarly assessed, considering MR-corrected data as reference. For the MR/CT workflow, both global and region of interest (ROI)-based MR/CT registration approaches were studied. RESULTS: In phantom measurements, the MR-corrected workflow demonstrated unsurpassed TLA (median offset of 0.2 mm) which deteriorated for MR-only and MR/CT workflows (median offsets of 0.8 and 0.6 mm, respectively). In real-patient cases, the MR-only workflow resulted in offsets that exhibit a significant positive correlation with the distance from the MR isocenter, reaching 1.1 mm (median 0.6 mm). Comparable results were obtained for the MR/CT-global workflow, although a maximum offset of 1.4 mm was detected. TLA was improved with the MR/CT-ROI workflow resulting in median/maximum offsets of 0.4 mm/1.1 mm. CONCLUSIONS: Subpixel TLA is achievable in all workflows. For the MR/CT workflow, a ROI-based MR/CT co-registration approach could considerably increase TLA and should be preferred instead of a global registration.

Molecular Epidemiology of SARS-CoV-2 in Greece Reveals Low Rates of Onward Virus Transmission after Lifting of Travel Restrictions Based on Risk Assessment during Summer 2020.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly during the first months of 2020 and continues to expand in multiple areas across the globe. Molecular epidemiology has provided an added value to traditional public health tools by identifying SARS-CoV-2 clusters or providing evidence that clusters based on virus sequences and contact tracing are highly concordant. Our aim was to infer the levels of virus importation and to estimate the impact of public health measures related to travel restrictions to local transmission in Greece. Our phylogenetic and phylogeographic analyses included 389 full-genome SARS-CoV-2 sequences collected during the first 7 months of the pandemic in Greece and a random collection in five replicates of 3,000 sequences sampled globally, as well as the best hits to our data set identified by BLAST. Phylogenetic trees were reconstructed by the maximum likelihood method, and the putative source of SARS-CoV-2 infections was inferred by phylogeographic analysis. Phylogenetic analyses revealed the presence of 89 genetically distinct viruses identified as independent introductions into Greece. The proportion of imported strains was 41%, 11.5%, and 8.8% during the three periods of sampling, namely, March (no travel restrictions), April to June (strict travel restrictions), and July to September (lifting of travel restrictions based on thorough risk assessment), respectively. The results of phylogeographic analysis were confirmed by a Bayesian approach. Our findings reveal low levels of onward transmission from imported cases during summer and underscore the importance of targeted public health measures that can increase the safety of international travel during a pandemic. IMPORTANCE Our study based on current state-of-the-art molecular epidemiology methods suggests that virus screening and public health measures after the lifting of travel restrictions prevented SARS-CoV-2 onward transmission from imported cases during summer 2020 in Greece. These findings provide important data on the efficacy of targeted public health measures and have important implications regarding the safety of international travel during a pandemic. Our results can provide a roadmap about prevention policy in the future regarding the reopening of borders in the presence of differences in vaccination coverage, the circulation of the virus, and the presence of newly emergent variants across the globe.

Cerebral thromboembolic risk in atrial fibrillation ablation: a direct comparison of vitamin K antagonists versus non-vitamin K-dependent oral anticoagulants.

PURPOSE: Cerebral thromboembolic events are well-known complications of pulmonary vein isolation (PVI) and can manifest as stroke or silent cerebral embolic lesions. The aim of this study was to compare the incidence of cerebral embolic lesions (including silent cerebral embolism and stroke) after AF ablation in patients on vitamin K antagonists versus patients on non-vitamin K-dependent oral anticoagulants, and to identify corresponding clinical and procedural risk factors. METHODS: A total of 421 patients undergoing PVI were prospectively included into the study. Of these, 43.7% were on VKA and 56.3% on NOAC treatment (dabigatran, rivaroxaban, apixaban, and edoxaban). In the NOAC group, 38% of patients had an interruption of anticoagulation for 24-36 h. All patients underwent pre- and postprocedural cerebral magnetic resonance imaging. RESULTS: Periprocedural cerebral lesions occurred in 13.1% overall. Of these, three (0.7%) resulted in symptomatic cerebrovascular accidents and 52 (12.4%) in silent cerebral embolic lesions. Incidence of cerebral lesions was significantly higher in patients on NOAC compared with VKA (16% vs. 9.2%, respectively, p = 0.04), and in patients who had intraprocedural cardioversions compared with no cardivoersions (19.5% vs. 10.4%, respectively, p = 0.03). In multivariate analysis, both parameters were found to be independent risk factors for cerebral embolism. No significant difference between interrupted and uninterrupted NOAC administration could be detected. CONCLUSIONS: In patients undergoing AF ablation, we identified the use of NOAC and intraprocedural cardioversion as independent risk factors for the occurrence of periprocedural cerebral embolic lesions.

Successful ablation of bifocal premature ventricular complexes from both left bundle branches triggering polymorphic ventricular tachycardia in long QT syndrome 2: a case report.

BACKGROUND: A 19-year-old woman with an established diagnosis of long QT syndrome (LQTS) 2 and underlying KCNH2-mutation was referred to our centre for recurrent polymorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) refractory to medical therapy and bilateral thoracic sympathectomy. CASE SUMMARY: Holter monitoring revealed a relevant premature ventricular complex (PVC) burden of two different morphologies. One PVC was originating from the left anterior fascicle, the other from the left posterior fascicle. Radiofrequency ablation resulted in complete suppression of both spontaneous PVC morphologies with a favourable clinical course over the next 2 years. DISCUSSION: This case presents two interesting insights: firstly, the consistent bigeminal pattern of the torsade de pointes triggering PVC. These were retrieved from the device interrogation and correlated with the pattern that was seen at the time of the procedure. Secondly, PVC morphologies suggested an origin from both the left ventricular (posterior and anterior) fascicles, which have not been described so far. This was confirmed by the preceding Purkinje potentials seen at the successful ablation sites in sinus rhythm and during PVC. Ablation of triggering PVCs causing recurrent VT/VF in LQTS 2 is feasible and effective over a mid-term follow-up.

Accelerating Physics-Based Simulations Using End-to-End Neural Network Proxies: An Application in Oil Reservoir Modeling.

We develop a proxy model based on deep learning methods to accelerate the simulations of oil reservoirs-by three orders of magnitude-compared to industry-strength physics-based PDE solvers. This paper describes a new architectural approach to this task modeling a simulator as an end-to-end black box, accompanied by a thorough experimental evaluation on a publicly available reservoir model. We demonstrate that in a practical setting a speedup of more than 2000X can be achieved with an average sequence error of about 10% relative to the simulator. The task involves varying well locations and varying geological realizations. The end-to-end proxy model is contrasted with several baselines, including upscaling, and is shown to outperform these by two orders of magnitude. We believe the outcomes presented here are extremely promising and offer a valuable benchmark for continuing research in oil field development optimization. Due to its domain-agnostic architecture, the presented approach can be extended to many applications beyond the field of oil and gas exploration.

Assessment of sequence dependent geometric distortion in contrast-enhanced MR images employed in stereotactic radiosurgery treatment planning.

This work focuses on MR-related sequence dependent geometric distortions, which are associated with B 0 inhomogeneity and patient-induced distortion (susceptibility differences and chemical shift effects), in MR images used in stereotactic radiosurgery (SRS) applications. Emphasis is put on characterizing distortion at target brain areas identified by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) paramagnetic contrast agent uptake. A custom-made phantom for distortion detection was modified to accommodate two small cylindrical inserts, simulating small brain targets. The inserts were filled with Gd-DTPA solutions of various concentrations (0-20 mM). The phantom was scanned at 1.5 T unit using both the reversed read gradient polarity (to determine the overall distortion as reflected by the inserts centroid offset) and the field mapping (to determine B 0 inhomogeneity related distortion in the vicinity of the inserts) techniques. Post-Gd patient images involving a total of 10 brain metastases/targets were also studied using a similar methodology. For the specific imaging conditions, contrast agent presence was found to evidently affect phantom insert position, with centroid offset extending up to 0.068 mm mM-1 (0.208 ppm mM-1). The Gd-DTPA induced distortion in patient images was of the order of 0.5 mm for the MRI protocol used, in agreement with the phantom results. Total localization uncertainty of metastases-targets in patient images ranged from 0.35 mm to 0.87 mm, depending on target location, with an average value of 0.54 mm (2.24 ppm). This relative wide range of target localization uncertainty results from the fact that the B 0 inhomogeneity distortion vector in a specific location may add to or partly counterbalance Gd-DTPA induced distortion, thus increasing or decreasing, respectively, the total sequence dependent distortion. Although relatively small, the sequence dependent distortion in Gd-DTPA enhanced brain images can be easily taken into account for SRS treatment planning and target definition purposes by carefully inspecting both the forward and reversed polarity series.

Feasibility of catheter ablation renal denervation in "mild" resistant hypertension.

Renal denervation (RDN) has been proposed as a novel interventional antihypertensive technique. However, existing evidence was mainly from patients with severe resistant hypertension. The authors aimed to evaluate the efficacy of RDN in patients with resistant hypertension with mildly elevated blood pressure (BP). Studies of RDN in patients with mild resistant hypertension (systolic office BP 140-160 mm Hg despite treatment with three antihypertensive drugs including one diuretic, or mean systolic BP by 24-hour ambulatory BP measurement [ABPM] 135-150 mm Hg) were included. Two observational and one randomized cohort were identified (109 patients in the RDN group and 36 patients in the control group). Overall, the mean age of patients was 62±10 years, and 69.7% were male. Before-after comparison showed that RDN significantly reduced ABPM as compared with the baseline systolic ABPM, from 146.3±13 mm Hg at baseline to 134.6±14.7 mm Hg at 6-month follow-up and diastolic ABPM from 80.8±9.4 mm Hg at baseline to 75.5±9.8 mm Hg at 6-month follow up (both P<.001). This significant effect was not observed in the control group. Between-group comparison showed a greater change in ABPM in the RDN group as compared with that in the control group (change in systolic ABPM: -11.7±9.9 mm Hg in RDN vs -3.5±9.6 mm Hg in controls [P<.001]; change in diastolic ABPM: -5.3±6.3 mm Hg in RDN vs -2.1±5.5 mm Hg in control [P=.007]). RDN was also associated with a significantly decreased office systolic/diastolic BP and reduced number of antihypertensive medications. No severe adverse events were found during follow-up. RDN seems feasible to treat patients with mild resistant hypertension.

Optimizing radiofrequency ablation of paroxysmal and persistent atrial fibrillation by direct catheter force measurement-a case-matched comparison in 198 patients.

BACKGROUND: Sufficient electrode-tissue contact is crucial for adequate lesion formation in radiofrequency catheter ablation (RFCA). OBJECTIVE: We assessed the impact of direct catheter force measurement on acute procedural parameters and outcome of RFCA for paroxysmal and persistent atrial fibrillation (AF). METHODS: Ninety-nine consecutive patients (70% men) with paroxysmal (63.6%) or persistent AF underwent left atrial RFCA using a 3.5-mm open-irrigated-tip (OIT) catheter with contact force measurement capabilities (group 1). For comparison a case-matched cohort with standard OIT catheters was used (99 patients; group 2). Case matching included gender, type of AF, number or RFCA procedures, and type of procedure. RESULTS: Procedural data showed a significant decline in radiofrequency ablation time from 52 ± 20 to 44 ± 16 minutes (P = 0.003) with a remarkable mean reduction in overall procedure time of 34 minutes (P = 0.0001; 225.8 ± 53.1 vs 191.9 ± 53.3 minutes). In parallel, the total fluoroscopy time could be significantly reduced from 28.5 ± 11.0 to 19.9 ± 9.3 minutes (P = 0.0001) as well as fluoroscopy dose from 74.1 ± 58.0 to 56.7 ± 38.9 Gy/cm(2) (P = 0.016). Periprocedural complications were similar in both groups. CONCLUSIONS: The use of contact force sensing technology is able to significantly reduce ablation, procedure, and fluoroscopy times as well as dose in RFCA of AF in a mixed case-matched group of paroxysmal and persistent AF. Energy delivery is substantially reduced by avoiding radiofrequency ablation in positions with insufficient surface contact. Additionally 12-month outcome data showed increased efficacy. Such time saving and equally safe technology may have a relevant impact on laboratory management and increased cost effectiveness.

Left-ventricular hypertrophy is associated better with 24-h aortic pressure than 24-h brachial pressure in hypertensive patients: the SAFAR study.

OBJECTIVE: To test the hypothesis that left-ventricular hypertrophy (LVH) is better associated with aortic, than brachial, 24-h average blood pressure (BP) in individuals with hypertension. BACKGROUND: The office aortic BP is associated better with organ damage, such as LVH, than the office brachial BP; whether the 24-h average aortic BP associates better with LVH, than the 24-h average brachial BP, has never been tested. METHODS: Aortic ambulatory BP monitoring (ABPM) was performed with a novel validated oscillometric cuff-based BP recording device, also used for simultaneous brachial ABPM, and the application of pulse wave analysis method. Office brachial and aortic BP were assessed with validated oscillometric recording device and pulse wave analysis, respectively; left-ventricular mass was measured by ultrasound. RESULTS: Regression analysis performed in 229 individuals (aged 54.3 ±â€Š14.6 years; 56% men; 75% hypertensive patients) showed that the 24-h average aortic SBP was significantly better associated with left-ventricular mass index and LVH than the 24-h average brachial, as well as, office (brachial or aortic) SBP, independently of age, sex, obesity or treatment. Receiver operator characteristics curve analysis showed a higher discriminatory ability of 24-h average aortic than brachial SBP to detect the presence of LVH (area under the curve: 0.73 versus 0.69; P = 0.007). A high degree of interindividual overlap regarding aortic 24-h average SBP level was found in individuals in whom the corresponding brachial measurements denoted different hypertension levels. CONCLUSION: These data suggest that aortic ABPM, when compared to brachial ABPM, improves the individualized assessment of the BP-associated heart damage.

Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion.

CONTEXT: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. OBJECTIVE: Our objective was to investigate CVR in patients with NFAI. DESIGN AND SETTING: This case-control study was performed in a tertiary general hospital. SUBJECTS: SUBJECTS included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. MAIN OUTCOME MEASURES: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. RESULTS: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. CONCLUSIONS: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.

Long-Term BMI changes since adolescence and markers of early and advanced subclinical atherosclerosis.

Although long-term weight gain has been associated with cardiovascular risk and intima-media thickening (IMT), no sufficient data exist on possible associations of such weight changes with more advanced stages of subclinical atherosclerosis. Moreover, the value of self-reported weight changes, a more practical approach to assess long-term history in adiposity status, is still a matter of debate. In this longitudinal study, long-term changes in BMI and overweight status were assessed in 106 healthy young adults (age 40.5 ± 1.1 years, 60 males). These were a subgroup of adolescent school students who had originally been examined in 1983 initially aiming to assess cardiovascular risk factor prevalence. Markers of early (carotid IMT) and advanced (presence of plaques in the carotid and femoral arteries and ankle-brachial index, ABI) subclinical atherosclerosis were measured in all individuals. By multivariate analysis, among other risk factors, IMT and the presence of plaques were independently determined by BMI change, while a low ABI was also determined by changes in overweight status. An adverse long term adiposity profile change (≥ +4 kg/m(2) and/or change into overweight/obese status from normal weight since adolescence) incrementally determined a low ABI over current risk factors. Self-reported and actual BMI changes were correlated (r = 0.587) but their means significantly differed, while the former significantly correlated with IMT only (P = 0.032). In conclusion, an adverse long term adiposity status change was more prominently associated with advanced subclinical atherosclerosis and particularly low ABI. These results also suggest that the utility of self-reported weight changes may be limited in primary prevention practice.

Pilot study of circulating prolactin levels and endothelial function in men with hypertension.

BACKGROUND: Hyperprolactinemia has been recently associated with hypertension and endothelial dysfunction in humans, confirming animal studies performed in the 1970s that showed high prolactin levels to exert positive chronotropic and vasoconstrictive effects. Whether prolactin affects endothelial function, in the absence of hyperprolactinemia, remains unknown. Considering that secretion of prolactin presents circadian rhythmicity, we tested the hypothesis that in patients with hypertension, who present diurnal variation in their endothelial function as well, prolactin levels correlate with endothelial function and/or blood pressure. METHODS: Endothelial function, assessed by flow-mediated dilatation (FMD) and serum prolactin were examined successively at 12 PM, 9 PM, and 7 AM in 27 nonhyperprolactinemic men with newly diagnosed, untreated essential hypertension. RESULTS: Both FMD and prolactin presented 24-h variation (P < 0.01). FMD reached its lowest values at 7 AM (2.1 ± 1.8%, mean ± s.d.); concurrently prolactin levels peaked (7.18 ng/ml, median). Across the three time points, prolactin changes inversely interacted with FMD changes (P = 0.002). Systolic and diastolic blood pressure also varied significantly but no interaction with prolactin changes was evident. CONCLUSIONS: Diurnal fluctuations of prolactin levels are associated with decreased endothelial function that occurs early in the morning in men with hypertension, although this study did not assess causality. Additional studies are required to determine whether these responses differ from normotensive individuals.

Time rate of blood pressure variation is superior to central hemodynamics as an associate of carotid intima-media thickness.

OBJECTIVE: The extent of target organ damage has been associated with both central hemodynamics and arterial stiffening, and the time rate of blood pressure (BP) changes in essential hypertension. However, the relative significance of these parameters has not been examined. METHODS: We recruited 232 consecutive uncomplicated newly diagnosed hypertensive patients and 241 normotensive individuals. Twenty-four-hour ambulatory BP monitoring was performed in all individuals. The time rate of SBP variation was computed as the first derivative of the SBP values against time. Aortic central SBP and central DBP, central pulse pressure, central augmentation index and central augmentation pressure were assessed noninvasively by pulse wave analysis. Common carotid artery intima-media thickness was measured by high-resolution ultrasonography. RESULTS: Median 24-h time rate of BP changes was 0.571 +/- 0.114 mmHg/min. Traditional risk factors, office SBP, several ambulatory BP monitoring parameters (24-h SBP, 24-h pulse pressure, 24-h heart rate and BP dipping), 24-h time rate of BP changes, time rate of BP changes at different time intervals, and central SBP, central pulse pressure, central augmentation index and central augmentation pressure significantly correlated with intima-media thickness. Age, sex, BMI, 24-h time rate of BP changes, time rate of BP changes measured at 0100-0600 h and 24-h heart rate remained significant associates of intima-media thickness after adjustment for confounding factors. By multivariate stepwise linear regression, 24-h time rate of BP changes and time rate of BP changes at 0100-0600 h had incremental value over traditional risk factors, other ambulatory BP monitoring parameters and central hemodynamics. CONCLUSION: These findings indicate that time rate of BP variation is superior to central hemodynamics as an associate of carotid intima-media thickness in hypertensive and normotensive individuals.