Reduction In Right Atrial Pressure Research Articles

Experience with percutaneous right ventricular support in the early post-left ventricular assist device implantation period (clinical case report and literature reviews)

Implantable left ventricular assist device (LVAD) is a state-of-the-art treatment for adults and children with end-stage heart failure. The early and late period after LVAD implantation can be severely complicated. Right ventricular failure (RVF) still remains a common complication after LVAD implantation. RVF is the cause of reduced post-implant survival. We suggest that an additional temporary or permanent right ventricular assist device (RVAD) is an effective treatment for LVAD-associated RVF. In this clinical case report, we describe the medical history of a pediatric patient (14 years old) with severe heart failure (PediMACS Level 1) against a background of dilated cardiomyopathy. The patient required peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) prior to urgent LVAD (HM3) implantation. In the early post-LVAD implantation (1 POD) period, the patient presented with hemodynamic and echocardiographic events of acute RVF that was resistant to drug therapy (inotropic/vasopressor support, iNO) and required mechanical circulatory support (MCS) with a preoperatively implanted VA-ECMO. In the LVAD-associated RVF scenario, VA-ECMO as a means of total cardiac bypass is a non-physiological MCS method and, therefore, undesirable. In this clinical situation, our solution was to use a paracorporeal centrifugal blood pump for temporary right heart support. A RVAD was assembled using percutaneous cannulation in two sites and a modification of the pre-existing VA-ECMO circuit. For RVAD, we used an ECMO cannula previously installed through the femoral vein (26 F) and added a reverse venous cannula (22 F) through the right internal jugular vein into the pulmonary trunk. To facilitate the passage of the return cannula into the pulmonary artery, we used a contralateral sheath (6 F, 40 cm) and an Amplatz Super Stiff guidewire under radiological control. The oxygenator was removed from the circuit on day 2 of RVAD. Central hemodynamics (reduction in right atrial pressure (RAP) to 10 mm Hg, increase in pulmonary capillary wedge pressure (PCWP) to 14 mm Hg), as well as right ventricular (RV) and left ventricular (LV) volume characteristics all improved. These observations allowed us to optimize the performance of the implantable LVAD (increase in flow rate to 4.2 l/min or 2.1 l/min/m2). The duration of paracorporeal RVAD after LVAD implantation was 7 days with an average flow rate of 2.3 ± 0.2 l/min. Postoperative treatment in the intensive care unit (ICU) lasted for 15 days. The patient was discharged from the hospital on postoperative day 34.

Venous Congestion, Not Cardiac Index is Associated with Diuretic Resistance

Background Diuretic resistance is associated with worse outcomes in acute decompensated heart failure (ADHF). Traditional dogma has held that low cardiac index (CI) is a driver of diuretic resistance by reducing renal perfusion. Recently, accumulating evidence has shown that venous congestion has a more potent effect on cardiorenal interactions than low CI. However, venous congestion also likely identifies patients with increased volume overload and the potential for a greater diuretic response. Hypothesis Right atrial pressure (RAP) will be associated with diuretic response while CI will have little to no association. Methods We analyzed a subset of patients from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) dataset (n=190). Diuretic efficiency (DE) was defined as daily urine output (UOP) per doubling of loop diuretic dose, and compared with baseline, final (day of pulmonary artery catheter (PAC) removal) and change in PAC variables. Daily UOP was additionally examined with time-matched PAC measurements. Results DE was weakly positively correlated with baseline RAP (r=0.16, p=0.03) but negatively correlated with final RAP (r=-0.21, p=0.009) and change in RAP from baseline (r=-0.27, p=0.001). There was no correlation between DE and the remaining PAC variables, including CI. In high vs. low DE groups dichotomized by median value, the low DE group had significantly higher final RAPs (9.0, IQR 6.0-15.5 mmHg vs. 8.0, IQR 4.8-12.0 mmHg, p=0.04) and smaller reductions in RAP (-2.0 mmHg, IQR-5.0-2.0 mmHg vs. -5.0, IQR=-10.0-0.0 mmHg, p=0.03). There were no DE group differences for baseline CI (p=0.78), final CI (p=0.42), or change in CI (p=0.92). There were no significant differences in DE in subjects with CI 2.2 L/min/m2 (p=0.95). Time-matched PAC and UOP data showed a weak positive correlation between RAP and UOP adjusted for diuretic dose (r=0.13, p=0.03), but no correlation between UOP and CI (p=0.18). Conclusions We were unable to identify any association between CI and DE. Higher baseline RAP predicted better DE, but later in the hospital course higher RAP predicted worse DE, likely indicating that elevated RAP is a marker rather than a mediator of diuretic response. Overall, these results suggest that PACs provide limited value in the workup of diuretic resistance.

Identification of physiologic treatment targets with favourable haemodynamic consequences in heart failure with preserved ejection fraction.

AimsHeart failure with preserved ejection fraction (HFpEF) is characterized by complex pathophysiology including an impaired diastolic reserve. We recently showed that milrinone favourably modifies filling pressures at rest and during exertion in HFpEF patients; however, the responsible mechanism is uncertain. The objective of this study was to develop a clearer understanding of the acutely modifiable physiologic parameters that may be targeted in HFpEF.Methods and resultsWe conducted computer modelling simulations based on invasive haemodynamic assessments, by right heart catheterization, in HFpEF patients at baseline and in response to milrinone. Our aim was to develop a detailed understanding of the physiologic mechanisms, which accounted for the observed actions. The resultant circulatory model of HFpEF encompassed the left ventricular (LV) end‐systolic and end‐diastolic pressure–volume relations, together with stressed blood volume, heart rate, and arterial mechanics. To support the modelled action of milrinone, we conducted complementary LV conductance catheter and echocardiography studies in sheep to evaluate LV end‐systolic and end‐diastolic pressure–volume relations. In HFpEF patients, the acute haemodynamic effects of intravenous milrinone (n = 10) administration compared with placebo (n = 10) included significant reductions in right atrial pressure (7 ± 1 to 3 ± 1 mmHg, P < 0.001) and pulmonary capillary wedge pressure (13 ± 1 to 8 ± 1 mmHg, P < 0.001), while cardiac index increased (2.77 ± 0.19 to 3.15 ± 0.14 L/min/m2, P < 0.05), and mean arterial pressure remained unchanged (95 ± 2 to 93 ± 3 mmHg, P = not significant). Computer simulations showed that these haemodynamic effects were explained by a concomitant 31% reduction in stressed blood volume together with 44% increase in LV end‐systolic elastance (LV E es). Individually, changes in these parameters were not sufficient to explain the haemodynamic effects of milrinone. In vivo studies conducted in sheep (n = 5) showed that milrinone reduced LV filling pressure (8.0 ± 0.8 to 2.7 ± 0.6 mmHg, P < 0.01) and increased LV E es (0.96 ± 0.07 to 2.07 ± 0.49, P < 0.05), while no significant effect on LV stiffness was observed (0.038 ± 0.003 to 0.034 ± 0.008, P = not significant).ConclusionsThese data demonstrate that stressed blood volume in HFpEF represents a relevant physiologic target in HFpEF; however, concomitant modulation of other cardiovascular parameters including LV contractility may be required to achieve desirable haemodynamic effects.

Use of Balloon Atrial Septostomy in Patients With Advanced Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

Despite the use and purported benefits of balloon atrial septostomy (BAS), its safety, efficacy, and therapeutic role in the setting of advanced pulmonary arterial hypertension (PAH) are not well defined. The goal of this study was to conduct a systematic review and meta-analysis to better determine the evidence supporting the use of BAS in PAH. MEDLINE, Scopus, Cochrane Library, and Clinicaltrials.gov were searched from inception through May 2018 for original studies reporting outcomes with PAH prior to and following BAS. Studies comparing BAS vsother septostomy procedures were excluded. Weighted mean differences and 95%CIs were pooled by using a random effects model. Sixteen studies comprising 204 patients (mean age, 35.8 years; 73.1%women) were included. Meta-analysis revealed significant reductions in right atrial pressure (-2.77mmHg [95% CI, -3.50, -2.04]; P< .001) and increases in cardiac index (0.62 L/min/m2 [95% CI, 0.48, 0.75]; P< .001) and left atrial pressure (1.86mmHg [95% CI, 1.24, 2.49]; P< .001) following BAS, along with a significant reduction in arterial oxygen saturation (-8.45%[95% CI, -9.93, -6.97]; P< .001). The pooled incidence of procedure-related (48 h), short-term (≤ 30day), and long-term (> 30days up to a mean follow-up of 46.5months) mortality was 4.8%(95% CI, 1.7%, 9.0%), 14.6%(95% CI, 8.6%, 21.5%), and 37.7%(95% CI, 27.9%, 47.9%), respectively. The present analysis suggests that BAS is relatively safe in advanced PAH, with beneficial hemodynamic effects. The relatively high postprocedural and short-term survival with less impressive long-term survival suggest a bridging role for BAS; its contribution to this change needs to be verified by using a comparator group.

How Dynamic are Hemodynamics?: Short-Term Changes in Hemodynamic Measures and Indices among Heart Failure Patients

Purpose Pulmonary arterial catheters (PAC) are valuable tools for guiding heart failure management and evaluating patients for advanced therapies. Although several hemodynamically-derived indices have prognostic value in patients with advanced heart failure, the short-term variance that can be seen in these measurements has not been well described. This study aimed to determine short-term variations in hemodynamic measurements and associated indices among heart failure patients. Methods Patients undergoing clinically-indicated PAC placement at our institution from April 2018 with serial hemodynamic measurements were prospectively recruited. Hemodynamics and clinical variables were collected at the time 0 and again at 24 hours. Hemodynamic indices frequently used to assess the right ventricle, including pulmonary artery pulsatility index (PAPi), right atrial pressure (RAP) to pulmonary capillary wedge pressure (PCWP) ratio, and transpulmonary gradient were also calculated for both time points. Results Data was available for 57 patients with an average of age 58.3 years. Compared to baseline measurements, 24-hour data revealed a significant reduction in RAP (-1.6 mmHg; p= Conclusion Our single-center experience with short-term hemodynamic measurements revealed improvement in filling pressures over 24 hours. Notably, in patients with initially elevated RAP, PAPi significantly improved. Such findings demonstrate that PAPi's utility as a risk prediction index must be considered in the context of its variability based on loading conditions, rather than as a static value.

UP-FRONT TRIPLE COMBINATION THERAPY FOR PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH SYSTEMIC SCLEROSIS: A CASE REPORT

Pulmonary arterial hypertension (PAH) is a progressive and irreversible disease characterized by a steady increase in pulmonary vascular resistance (PVR) and death. Introduction of current PAH-specific drugs has not solved the problem of follow-up of critical patients with PAH associated with systemic sclerosis (SSc). Clinical trials have shown that 1-, 2- and 3-year survival rates are 77, 46, and 33%, respectively. Arguments in favor of starting triple PAH-specific therapy that substantially improves the prognosis of this critical group of patients are being accumulated. The paper describes Russia’s first clinical case of successful up-front triple combination therapy (iloprost, bosentan and sildenafil) in a 40 year old female with SSc and diagnosed functional class (FC) IV PAH. There were clinical, laboratory, and hemodynamic improvements already at 2 weeks after therapy initiation. Thirty-month therapy resulted in a reversal of FC from IV to II, relieved the signs of right ventricular failure, complete right ventricular reverse remodeling and subnormalization of hemodynamic parameters. Hemodynamic improvement including reductions in right atrial pressure to 4 mm Hg, mean pulmonary arterial pressure to 26 mm Hg, and PVR to 2.2 Wood units and an increase in cardiac output up to 7.4 l/min, despite preserved elevated uric acid levels (432 μmol/l). The intriguing feature of this case is critically low values of % predicted/carbon monoxide lung diffusion capacity, which rose from 17% to only 22%, in the presence of positive changes. This clinical case demonstrates the predictive capabilities of up-front triple combination therapy for severe PAH associated with SSc.

The Striking Interplay of Hiccup and Patent Foramen Ovale

Previous studies have shown that reducing intrathoracic pressure during inspiration significantly increases right atrial volume (through an increase in venous return) with a slight reduction of right atrial pressure [(1)][1]. In patients with an atrial septal defect, the same phasic, inspiration-

The effect of left ventricular assist device therapy in patients with heart failure and mixed pulmonary hypertension.

Diastolic pressure gradient (DPG) of ≥7 mmHg has been proposed to distinguish mixed pulmonary hypertension from isolated post-capillary pulmonary hypertension in heart failure (HF). We evaluated the changes in pulmonary hemodynamics with left ventricular assist devices (LVADs) in patients with DPG of ≥7 or <7 mmHg, and effects on peak oxygen uptake (VO2) in patients with advanced HF. Pre- and post-LVAD implant pulmonary hemodynamics (including right atrial (RA) pressures, DPG, pulmonary vascular resistance (PVR), pulmonary capacitance (PCap) and cardiac output), echocardiography, cardiopulmonary exercise test were measured in 38 consecutive patients. Ten of 38 patients had baseline DPG ≥7 mmHg. There were no significant difference in baseline characteristics, peak VO2 and ventilation slope, but PVR were higher, and PCap lower in patients with DPG ≥7 mmHg. Pulmonary artery pressures improved in all patients, but PVR and DPG remained higher and PCap lower in patients with baseline DPG ≥7 mmHg after a median follow-up of 181 (IQR 153-193) days. Peak VO2 increased and ventilation slope reduced post-LVAD, and these improvements were comparable between groups. Only RA pressure reduction and exercise increase in heart rate were significant predictors of peak VO2 increase on multivariate analysis. Baseline DPG of ≥7 mmHg compared to DPG <7 mmHg have persistently lower PCap and higher PVR post-LVAD, but the increase in peak VO2 was comparable despite these residual pulmonary vascular abnormalities. The improvement in peak VO2 was related to reduction in right atrial pressure and exercise increase in heart rate.

Serial semi-invasive hemodynamic assessment following pericardiectomy for chronic constrictive pericarditis

Objectives:This study was designed to prospectively investigate the effects of pericardiectomy via median sternotomy on intra- and postoperative hemodynamics by a new semi-invasive device (Flotrac/VigileoTM monitor) using arterial pressure waveform analysis.Patients and Methods:Thirty consecutive patients aged 15 to 55 years (mean+SD, 31.73 + 13.53 years), who had undergone total pericardiectomy via median sternotomy underwent serial hemodynamic evaluation. FlotracTM Sensor – derived stroke volume, stroke volume variation, systemic vascular resistance index (SVRI), cardiac index and right atrial pressure were measured just before and after pericardiectomy, at 12 hours, 24 hours, 48 hours, 72 hours and at discharge postoperatively.Results:Majority of patients (73.33%) exhibited statistically significant reduction of right atrial pressure and SVRI along with improvement in cardiac index and oxygen delivery in the immediate and late postoperative period. However, the stroke volume and stroke volume variation did not increase proportionately on completion of surgery. Patients with low cardiac output syndrome exhibited persistently high central venous pressure with reduced cardiac index and echocardiographically abnormal diastolic filling characteristics.Conclusions:We conclude that there is early normalization of hemodynamics following pericardiectomy via median sternotomy and the adequacy of pericardiectomy can be accurately assessed by the new semi-invasive arterial pressure waveform analysis device. Stroke volume variation is a non-predictor of fluid requirement during and after pericardiectomy.

Hemodynamic challenge to early mobilization after cardiac surgery: A pilot study

Background:Active mobilization is a key component in fast-track surgical strategies. Following major surgery, clinicians are often reluctant to mobilize patients arguing that circulatory homeostasis would be impaired as a result of myocardial stunning, fluid shift, and autonomic dysfunction.Aims:We examined the feasibility and safety of a mobilization protocol 12–24 h after elective cardiac surgery.Setting and Design:This observational study was performed in a tertiary nonacademic cardiovascular Intensive Care Unit.Materials and Methods:Over a 6-month period, we prospectively evaluated the hemodynamic response to a two-staged mobilization procedure in 53 consecutive patients. Before, during, and after the mobilization, hemodynamics parameters were recorded, including the central venous oxygen saturation (ScvO2), lactate concentrations, mean arterial pressure (MAP), heart rate (HR), right atrial pressure (RAP), and arterial oxygen saturation (SpO2). Any adverse events were documented.Results:All patients successfully completed the mobilization procedure. Compared with the supine position, mobilization induced significant increases in arterial lactate (34.6% [31.6%, 47.6%], P = 0.0022) along with reduction in RAP (−33% [−21%, −45%], P < 0.0001) and ScvO2 (−7.4% [−5.9%, −9.9%], P = 0.0002), whereas HR and SpO2 were unchanged. Eighteen patients (34%) presented a decrease in MAP > 10% and nine of them (17%) required treatment. Hypotensive patients experienced a greater decrease in ScvO2 (−18 ± 5% vs. −9 ± 4%, P = 0.004) with similar changes in RAP and HR. All hemodynamic parameters, but arterial lactate, recovered baseline values after resuming the horizontal position.Conclusions:Early mobilization after cardiac surgery appears to be a safe procedure as far as it is performed under close hemodynamic and clinical monitoring in an intensive care setting.

First-in-Human Transcatheter Tricuspid Valve Repair in a Patient With Severely Regurgitant Tricuspid Valve

BackgroundSevere tricuspid regurgitation is associated with poor prognosis; however, there are limited Class I indications for intervention, and high–surgical risk patients may go untreated. We report the first-in-human successful transcatheter tricuspid valve repair for severe tricuspid regurgitation. ObjectivesThe objective of this study was to show the feasibility of a transcatheter tricuspid annular repair. MethodsCompassionate-use approval for the procedure was obtained from the regulatory organization in Germany. To perform the transcatheter bicuspidization of the tricuspid valve, the Mitralign system was used to place pledgeted sutures by means of a trans-jugular venous approach. Insulated radiofrequency wires were positioned 2 to 5 mm from the base of the posterior leaflet, 2.6 cm apart. The sutures were drawn together and locked, plicating the posterior annulus. ResultsReconstruction of the 3-dimensional transesophageal echocardiographic dataset at baseline revealed a tricuspid valve annular area of 14.1 cm2, and effective regurgitant orifice area was 1.35 cm2. There was a significant reduction in annular area (57%) and effective regurgitant orifice area (53%) measured with 3-dimensional transesophageal echocardiography, at 6.05 cm2 and 0.63 cm2, respectively. Hemodynamic parameters also improved with a reduction in right atrial pressure from 22 mm Hg at baseline, to 9 mm Hg and an increase in left ventricular stroke volume from 42 ml at baseline to 72 ml. ConclusionsTranscatheter tricuspid valve repair could become an effective treatment for high–surgical risk patients who are non-responsive to optimal medical therapy.

Fluid loss, venous congestion, and worsening renal function in acute decompensated heart failure

To investigate the relationship between decongestion, central venous pressure, and risk of worsening renal function (WRF) in patients with acute decompensated heart failure (ADHF). We studied 475 patients with ADHF, of whom 238 underwent right heart catheterization. Right atrial pressure (RAP) was measured at baseline and at 24 h. Net fluid loss was recorded in the first 24 h. WRF was defined as a >0.3 mg/dL increase in serum creatinine above baseline. WRF occurred in 84 catheterized patients (35.3%). There was a weak correlation between baseline RAP and baseline estimated glomerular filtration rate (r = -0.17, P = 0.009). The amount of fluid removed during the first 24 h did not correlate with the magnitude of RAP reduction (r = 0.06, P = 0.35). No association was observed between WRF and baseline RAP [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.80-1.41, P = 0.68 per 6.6 mmHg] or the decrease in RAP (adjusted OR 1.13, 95% CI 0.85-1.49, P = 0.40 per 5.3 mmHg reduction in RAP). In contrast, smaller net fluid loss was strongly associated with increased WRF risk. Compared with the first net fluid loss tertile, the adjusted OR was 1.85 (95% CI 0.90-3.80, P = 0.10) and 2.58 (95% CI 1.27-5.25; P = 0.009) for the second and third tertile, respectively (P for trend <0.0001). Smaller early net fluid loss is associated with increased risk for WRF. RAP is not a reliable surrogate of the magnitude of decongestion and risk of WRF. Future research is necessary to determine if targeting congestion may help prevent WRF.

Concomitant Tricuspid Valve Repair or Replacement During Left Ventricular Assist Device Implant Demonstrates Comparable Outcomes in the Long Term

Severe tricuspid regurgitation (TR) is present in nearly half the patients undergoing implant of a left ventricular assist device (LVAD) and its correction confers better long-term outcome. To compare the early and late results of tricuspid valve repair (TVrpr) or replacement (TVR) with LVAD implant. Sixty-four from a cohort of 126 patients had a concomitant tricuspid valve procedure; 48 (75%) underwent a TVrpr whereas 16 (25%) had TVR. All preoperative hemodynamic parameters including the mean TR grade (TVrpr; 3.6 vs. TVR; 3.7) were comparable (p = 0.7). The mean TR grade was 1.6 ± 1.5 for the remaining 62 patients who did not have a concomitant tricuspid valve procedure, with 4/62 (6%) having severe TR (p < 0.0001). Cardiopulmonary bypass time was longer for patients undergoing TVR (p = 0.01). There was a significant reduction in right atrial pressure for the entire cohort (p < 0.01) and the postoperative right atrial pressure was not statistically different between TVrpr (13.6 ± 4.6) and TVR (11.6 ± 4.3; p = 0.6. Postoperative intensive care unit stay was comparable as was the duration of inotropic support (p = 0.5) or need for temporary right ventricular mechanical support. In-hospital mortality (12%) was not different between groups. The mean time for LVAD support was 12.3 ± 9.71 months and the last transthoracic echocardiographic examination was performed at mean intervals of 13.8 ± 10.8 months (TVrpr) and 11.8 ± 7.6 months (TVR; p = 0.47). Reduction in TR grade was similar between groups (p = 0.27). Late mortality (p = 1.00) was comparable in both groups. Using log-rank analysis, there was no significant difference in the estimated survival between TVrpr and TVR (p = 0.88). TVrpr repair at the time of LVAD implant is effective in correcting TR even at the end of one year of follow-up. The choice to repair or replace does not affect the clinical outcome.

Effects of the HeartMate II continuous-flow left ventricular assist device on right ventricular function

Continuous-flow devices have become the standard of care for mechanical circulatory support for end-stage heart failure patients because of improved survival and durability. The effects of these devices, such as the HeartMate II (HMII) left ventricular assist device (LVAD), on right ventricular (RV) function have not been evaluated in detail. This study evaluated the incidence of RV failure, alterations in RV function, severity of tricuspid regurgitation (TR), and cardiac hemodynamics after HMII implantation. Echocardiograms (n = 22) and right heart catheterizations (n = 40) were performed before and after 4 to 6 months of HMII support in 40 bridge-to-transplant patients. Right heart failure was defined as the requirement for inotropes and/or nitric oxide requirement after LVAD implantation for >14 days or the need for right-sided mechanical circulatory support. Overall, RV failure after HMII implantation occurred in 2 of 40 patients (5%). Significant improvements occurred in cardiac index, with reductions in right atrial pressure, RV stroke work index, tricuspid annular motion, mean pulmonary artery pressure, and pulmonary vascular resistance after HMII support. There was a trend towards reduction in TR after LVAD support (p = 0.075). The incidence of RV failure after support with continuous-flow devices such as the HMII is low. The favorable effects of the HMII on cardiac hemodynamics result in improved RV function, improved right- and left-sided hemodynamic profiles, and a reduction in TR severity. These findings may have important implications for LVAD patients needing longer-term support.

Noninvasive Assisted Ventilation in Pulmonary Gas Exchange Dysfunctions in Cardiac Surgical Patients

Background. Postextubation pulmonary gas exchange dysfunctions are a potential complication in the activation of cardio-surgical patients in the early periods after surgical intervention. Objective: to evaluate the efficiency of noninvasive assisted ventilation (NIAV) as a method for correcting the pulmonary gas exchange disturbances developing after early activation of cardiosurgical patients. Subjects and methods. The study included 64 patients (36 males and 28 females) aged 21 to 72 (54±2) years who had been operated on under extracorporeal circulation (EC). The duration of EC and myocardial ischemia was 104±6 and 73±4 min, respectively. The indications for NIAV were the clinical manifestations of acute respiratory failure (ARF) and/or PaCO2>50 mm Hg and/or PaO2/FiO2Results. During NIAV, there was improvement (p 50 mm Hg) an hour after initiation of NIAV. During and after NIAV, there were reductions in right atrial pressure, mean pulmonary pressure, indexed total pulmonary vascular resistance (ITPVR) (p<0.05). Prior to, during, and following NIAV, mean blood pressure, cardiac index, and indexed total pulmonary vascular resstance did not change greatly. In hypercapnia, the duration of NIAV was significantly less than that in lung oxygenizing function (2.8±0.2 hours versus 4.7±0.5 hours). That of ICU treatment was 23±4 hours. Fifty-two (81%) patients were transferred from ICUs to cardiosurgical units on the following day after surgery. Conclusion. In most cases, NIAV promotes a rapid and effective correction of postextubation lung ventilatory and oxygenizing dysfunctions occurring after early activation of cardiosurgical patients. Key words: non-invasive assisted ventilation, early activation of cardiosurgical patients.

Nesiritide in infants and children with congestive heart failure*

Nesiritide (synthetic B-type natriuretic peptide) has been shown to be effective in the management of acute decompensated heart failure in adults. The role of nesiritide in pediatric heart failure has not been examined. In the present study, we reviewed our initial experience with nesiritide in children with primary heart failure or low cardiac output after heart surgery. Nesiritide was administered in an open-label fashion to patients with heart failure who were already receiving inotropic and diuretic therapy. Between July 2003 and August 2004, 30 patients aged 5 days to 16.7 yrs (median age, 4.6 months) received nesiritide therapy. Diagnoses included single-ventricle congenital defect (n = 5), two-ventricle congenital defect (n = 13), heart transplant (n = 5), and dilated cardiomyopathy (n = 7). Sixteen patients were started on nesiritide within 2 wks of corrective or palliative heart surgery. The majority of subjects (n = 24) received an initial bolus dose. Continuous infusion dosage ranged between 0.005 and 0.02 microg.kg.min. Nesiritide was discontinued for possible side effects in two patients (arrhythmia and hypotension). Duration of therapy ranged from 1 to 24 days (median, 4 days). Administration of nesiritide was associated with improvement in fluid balance from positive 0.8 +/- 1.9 mL.kg.hr at baseline to negative 0.3 +/- 1.8 mL.kg.hr after 24 hrs of therapy (p = .02). There was a nonsignificant trend toward a reduction in right atrial pressure (9.2 +/- 3.9 vs. 11.2 +/- 4.1, p = .08). Nesiritide is well tolerated in children with heart failure and is associated with improved diuresis. Further prospective studies will be needed to compare nesiritide with other vasoactive agents and examine the cost-efficacy of this therapy.

Acute NEP/ACE inhibition by omapatrilat is superior to ace inhibition alone in mediating favorable cardiorenal and humoral actions in mild heart failure

Mild heart failure (HF) is characterized by increases in the cardiac peptides ANP and BNP without activation of the renin-angiotensin-aldosterone system (RAAS). Both ANP and BNP, which possess natriuretic, vasodilating and renin inhibiting properties, are degraded by neutral endopeptidase 24.11 (NEP). Omapatrilat (OMA) is the first of a novel class of cardiovascular agents that inhibit both NEP and angiotensin-converting enzyme (ACE). As the RAAS is not activated in mild HF, we hypothesized that dual NEP-ACE inhibition will result in greater cardiorenal and humoral actions as compared to ACE inhibition alone. We compared the cardiorenaI and humoral actions of OMA (1 txmol/kg iv bolus) (n-6), to ACE inhibition(ACEI) with Fosinoprilat (1 /~mol/kg iv bolus) (n 5), in anaesthetized dogs with mild HF produced by rapid ventricular pacing at 180 beats/min for 10 days. OMA resulted in a greater natriuretic response as compared with ACEI (78+15 vs 3229/xEq/min, p<0.05). This OMA mediated natriuresis was associated with increased plasma cGMP (18+3 to 25292 pmol/mI*), ANP (144---15 to 259+ 14 pg/ml*) and BNP (100-+ 18 to 152233 pg/ml*) levels, urinary cGMP (13842250 to 2408-+514 pmol/min*) and urinary ANP (33210 to 125--40 pg/min*) excretion and glomerular filtration rate (30-+4 to 4725 ml/min*) (* p<0.05 vs baseline). Pulmonary capillary wedge pressure (1522 to 11-+1 mmHg, p<0.05) decreased only in the OMA group while the reduction in right atrial pressure was more sustained with OMA as compared ACEI. Plasma renin and aldosterone levels were increased only in the ACEI group (p<0.05 vs baseline). This study reports for the first time that acute OMA administration in mild HF results in a greater natriurefic response as compared to ACEI and is associated with reductions in cardiac filling pressures. These favorable actions occur secondary to the potentiation of the natriuretic peptides as evident by the increase in plasma and urinary excretion of both the natriuretic peptides and their second messenger cGMP. Furthermore, unlike ACEI, there is no activation of renin and aldosterone with OMA. This study provides new insight into a unique new compound that has beneficial actions in mild heart failure beyond those observed with ACE inhibition alone. The Third Annual Scientific Meeting • HFSA 13

Effect of furosemide and subsequent intravenous fluid administration on right atrial pressure of splenectomized horses

Abstract Objective To investigate the effect of IV administration of fluids on the furosemide-induced reduction in right atrial pressure (RAP) and relative change in blood volume (BV) of splenectomized mares. Animals 5 splenectomized mares. Procedure RAP was measured by use of a micromanometer placed in the right atrium. Jugular venous blood was collected for measurement of hematocrit, plasma total protein concentration, and hemoglobin concentration. Right atrial pressure was recorded and blood samples were collected immediately before furosemide (1 mg/kg of body weight, IV) administration, then every 15 minutes for 240 minutes. Beginning 120 minutes after furosemide administration, polyionic fluids (lactated Ringer's solution) were administered (2 L q 15 min) for 120 minutes. Results Furosemide induced a significant (P &lt; 0.05) decrease in mean RAP (7.6 ± 1.5 and 3.2 ± 1.2 mm of Hg before and 15 minutes after furosemide administration, respectively), and BV (8.4 ± 1.1 % by 15 minutes). Polyionic fluid administration restored RAP and BV The volume of polyionic fluids administered (32 ± 2 ml/kg) was not significantly different from the volume of urine produced (38 ± 7.8 ml/kg). Difference was not apparent in the relation between change in BV and RAP before or after fluid administration. Conclusions The effect of furosemide on RAP of horses is mediated in large part by furosemide-induced reduction in BV. However, an effect of furosemide on venous compliance cannot be excluded as contributing to the reduction in RAP. (Am J Vet Res 1997;58:632–635)

Inhaled Nitric Oxide Improves Hepatic Tissue Oxygenation in Right Ventricular Failure

Inhaled Nitric Oxide Improves Hepatic Tissue Oxygenation in Right Ventricular Failure

Haemodynamic effects of glyceryl trinitrate during continuous 24 hour infusion in patients with heart failure.

To investigate whether the susceptibility to tolerance to glyceryl trinitrate is similar in different vascular beds in patients with chronic heart failure. Twenty patients with heart failure underwent a continuous infusion of glyceryl trinitrate over 24 hours followed by administration of N-acetylcysteine (5 g intravenously) in a bolus. Haemodynamic measurements under control conditions, at peak titration of glyceryl trinitrate at 24 hours, and after N-acetylcysteine; plasma renin activity and packed cell volume. After 24 hours of infusion the acute reduction in right atrial pressure had largely waned, while pulmonary vascular resistance remained improved and systemic resistance, which was not reduced at peak titration, significantly decreased with respect to control conditions. The effects of N-acetylcysteine and hormonal responses were different in patients who did and did not develop tolerance to glyceryl trinitrate. The haemodynamic profile of glyceryl trinitrate changed substantially during the study from a predominantly venodilator action at peak titration to a predominantly arteriolar dilatation after 24 hours of infusion. The different effects of N-acetylcysteine and the different hormonal responses confirm the multifactorial pathogenesis of tolerance to glyceryl trinitrate.