Aims To evaluate the safety and effectiveness of pulmonary vein isolation in paroxysmal atrial fibrillation (PAF) using a standardized workflow aiming to enclose the veins with contiguous and optimized radiofrequency lesions. Methods and results This multicentre, prospective, non-randomized study was conducted at 17 European sites. Pulmonary vein isolation was guided by VISITAG SURPOINT (VS target ≥550 on the anterior wall; ≥400 on the posterior wall) and intertag distance (≤6 mm). Atrial arrhythmia recurrence was stringently monitored with weekly and symptom-driven transtelephonic monitoring on top of standard-of-care monitoring (24-h Holter and 12-lead electrocardiogram at 3, 6, and 12 months follow-up). Three hundred and forty participants with drug refractory PAF were enrolled. Acute effectiveness (first-pass isolation proof to a 30-min wait period and adenosine challenge) was 82.4% [95% confidence interval (CI) 77.4–86.7%]. At 12-month follow-up, the rate of freedom from any documented atrial arrhythmia was 78.3% (95% CI 73.8–82.8%), while freedom from atrial arrhythmia by standard-of-care monitoring was 89.4% (95% CI 78.8–87.0%). Freedom fromrepeat ablations by the Kaplan–Meier analysis was 90.4% during 12 months of follow-up. Of the 34 patients with repeat ablations, 14 (41.2%) demonstrated full isolation of all pulmonary vein circles. Primary adverse event (PAE) rate was 3.6% (95% CI 1.9–6.3%). Conclusions The VISTAX trial demonstrated that a standardized PAF ablation workflow aiming for contiguous lesions leads to low rates of PAEs, high acute first-pass isolation rates, and 12-month freedom from arrhythmias approaching 80%. Further research is needed to improve the reproducibility of the outcomes across a wider range of centres. Clinical trial registration: ClinicalTrials.gov, number NCT03062046, https://clinicaltrials.gov/ct2/show/NCT03062046.

The relative importance of systemic volume, concentration, and pressure signals in sodium homeostasis was investigated by intravenous infusion of isotonic (IsoLoad) or hypertonic (HyperLoad) saline at a rate (1 micromol Na(+) x kg(-1) x s(-1)), similar to the rate of postprandial sodium absorption. IsoLoad decreased plasma vasopressin (-35%) and plasma ANG II (-77%) and increased renal sodium excretion (95-fold), arterial blood pressure (DeltaBP; +6 mmHg), and heart rate (HR; +36%). HyperLoad caused similar changes in plasma ANG II and sodium excretion, but augmented vasopressin (12-fold) and doubled DeltaBP (+12 mm Hg) without changing HR. IsoLoad during vasopressin clamping (constant vasopressin infusion) caused comparable natriuresis at augmented DeltaBP (+14 mm Hg), but constant HR. Thus vasopressin abolished the Bainbridge reflex. IsoLoad during normotensive angiotensin clamping (enalaprilate plus constant angiotensin infusion) caused marginal natriuresis (9% of unclamped response) despite augmented DeltaBP (+14 mm Hg). Cessation of angiotensin infusion during IsoLoad immediately decreased BP (-13 mm Hg) and increased glomerular filtration rate by 20% and sodium excretion by 45-fold. The results suggest that fading of ANG II is the cause of acute "volume-expansion" natriuresis, that physiological ANG II deviations override the effects of modest systemic blood pressure changes, and that endocrine rather than hemodynamic mechanisms are the pivot of normal sodium homeostasis.

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day _1 ) received isotonic saline intravenously (NaLoading: 20 mmol Na + kg _1 min _1 or ~11 ml min _1 for 240 min). NaLoading did not change MAP or GFR (by clearance of 51 Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 ± 3 to 13 ± 2 mmol min _1 ). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R = 0.997) as were ANGII and aldosterone (R = 0.999). The slopes were 0.40 pM ANGII (mi.u. renin activity) _1 and 22 pM aldosterone (pM ANGII) _1. Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO x ). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP-and NO x excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.

Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 micromol x kg(-1) x min(-1)) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively). Mean arterial blood pressure did not change with any infusion of 6 or 20 micromol x kg(-1) x min(-1). During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14+/-2 to 7+/-2 pg/ml and sodium excretion increased markedly (2.3+/-0.8 to 19+/-8 micromol/min), whereas glomerular filtration rate (GFR) remained constant. IsoLoad-20 decreased plasma ANG II similarly (13+/-3 to 7+/-1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9+/-1.0 to 11+/-6 micromol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mm Hg and decreased plasma ANG II to approximately 6 pg/ml, whereas sodium excretion increased to approximately 60 micromol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry.

Objective. Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction. Methods. In a cross-sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac Results. Compared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P 5 0.02) and longer QRS and QT intervals (P 5 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P 5 0.001), disease duration (P 5 0.004), presence of myositis-specific or -associated autoantibodies (P 5 0.05), and high cardiac 99m Tc-PYP uptake (P 5 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD. Conclusion. Patients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis-specific or -associated autoantibodies and high cardiac 99m Tc-PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin-angiotensin-aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species-specific.

We studied the effects of 3-h infusions of ANG III, ANG-(1-7), and ANG IV in doses equimolar to physiological amounts of ANG II (3 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), in six men on low-sodium diet (30 mmol/ day). The subjects were acutely pretreated with canrenoate and captopril to inhibit aldosterone actions and ANG II synthesis, respectively. ANG II infusion increased plasma angiotensin immunoreactivity to 53 Ϯ 6 pg/ml (ϩ490%), plasma aldosterone to 342 Ϯ 38 pg/ml (ϩ109%), and blood pressure by 27%. Glomerular filtration rate decreased by 16%. Concomitantly, clearance of endogenous lithium fell by 66%, and fractional proximal reabsorption of sodium increased from 77 to 92%; absolute proximal reabsorption rate of sodium remained constant. ANG II decreased sodium excretion by 70%, potassium excretion by 50%, and urine flow by 80%, whereas urine osmolality increased. ANG III also increased plasma aldosterone markedly (ϩ45%), however, without measurable changes in angiotensin immunoreactivity, glomerular filtration rate, or renal excretion rates. During vehicle infusion, plasma renin activity decreased markedly (ϳ700 to ϳ200 mIU/l); only ANG II enhanced this decrease. ANG-(1-7) and ANG IV did not change any of the measured variables persistently. It is concluded that 1) ANG III and ANG IV are cleared much faster from plasma than ANG II, 2) ANG II causes hypofiltration, urinary concentration, and sodium and potassium retention at constant plasma concentrations of vasopressin and atrial natriuretic peptide, and 3) a very small increase in the concentration of ANG III, undetectable by usual techniques, may increase aldosterone secretion substantially. healthy humans; angiotensin peptides; aldosterone secretion; sodium excretion THE RENIN-ANGIOTENSIN-ALDOSTERONE system (RAAS) is the single most important regulator of the sodium homeostasis. This specific role of the RAAS makes it a major determinant of extracellular fluid volume and arterial blood pressure. It has long been recognized that ANG II is the pivotal component of this system.

Wamberg, Christian, Ronni R. Plovsing, Niels C. F. Sandgaard, and Peter Bie. Effects of different angiotensins during acute, double blockade of the renin system in conscious dogs. Am J Physiol Regul Integr Comp Physiol 285: R971-R980, 2003. First published July 17, 2003 10.1152/ ajpregu.00262.2003.-Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 Ϯ 19 and 274 Ϯ 13 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , respectively) than for ANG II (107 Ϯ 13 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ). ANG II increased ANG IR by 60 Ϯ 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 Ϯ 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 Ϯ 2 to 33 Ϯ 2 ml/min), sodium excretion (50 Ϯ 7 to 16 Ϯ 4 mol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 Ϯ 8 to 19 Ϯ 3 mol/min) and aldosterone secretion (to 268 Ϯ 71 pg/ml) at much lower ANG IR increments (ϳ1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved. sodium excretion; antidiuresis; blood pressure; angiotensin peptides; metabolic clearance rate THE RENIN-ANGIOTENSIN-ALDOSTERONE system (RAAS) plays a major role in defense of extracellular fluid volume and cardiovascular function. ANG II induces sodium retention and decreases renal blood flow, glomerular filtration rate (GFR), general systemic vasoconstriction, secretion of aldosterone from the adrenal cortex, and possibly release of vasopressin from the pituitary gland (35).