Acute Volume Overload Research Articles

The natural matching of harmonic responses in the pulmonary circulation.

Key points The right ventricle of the mammal heart is highly sensitive to the afterload imposed by a combination of the pulmonary circulation and the retrograde contribution of the left heart.Right ventricular afterload can be analysed in terms of pulmonary artery input impedance, which we were able to decompose as the result of the harmonic frequency responses of the pulmonary vessels and the left heart attached in series.Using spectral methods, we found a natural matching between the pulmonary vasculature and the left chambers of the heart. This coupling implies that the upstream transmission of the left heart frequency‐response has favourable effects on the pulmonary tree.This physiological mechanism protects the right ventricle against acute changes in preload, and its impairment may be a relevant contribution to right ventricle dysfunction in pulmonary hypertension. The right ventricle (RV) of the mammal heart is highly sensitive to the afterload imposed by the pulmonary circulation, and the left heart (LH) retrogradely contributes significantly to this vascular load. Transmission‐line theory anticipates that the degree of matching between the frequency responses of the pulmonary vasculature and the LH should modulate the global right haemodynamic burden. We measured simultaneous high‐fidelity flow (pulmonary artery) and pressure (pulmonary artery and left atrium) in 18 healthy minipigs under acute haemodynamic interventions. From these data, we decomposed the impedance spectra of the total right‐circulation system into the impedance of the pulmonary vessels and the harmonic response of the LH. For frequencies above the first harmonic, total impedance was below the pulmonary impedance during all phases (P < 0.001; pooled phases), demonstrating a favourable effect of the LH harmonic response on RV pulsatile load: the LH harmonic response was responsible for a 20% reduction of pulse pulmonary artery pressure (P < 0.001 vs. a theoretical purely‐resistive response) and a 15% increase of pulmonary compliance (P = 0.009). This effect on compliance was highest during acute volume overload. In the normal right circulation, the longitudinal impedance of the pulmonary vasculature is matched to the harmonic response of the LH in a way that efficiently reduces the pulmonary pulsatile vascular load. This source of interaction between the right and left circulations of mammals protects the RV against excessive afterload during acute volume transients and its disruption may be an important contributor to pulmonary hypertension.

Effect of acute volume overload on echocardiographic indices of right ventricular function and dyssynchrony assessed by use of speckle tracking echocardiography in healthy dogs.

OBJECTIVE To determine the relationship between acute volume overload and echocardiographic indices of right ventricular (RV) function and dyssynchrony in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES Right heart catheterization and echocardiography were performed in 7 healthy anesthetized Beagles at baseline and after induction of volume overload. Volume overload was induced by IV infusion of lactated Ringer solution (150 mL/kg/h for 90 minutes). Echocardiographic indices of RV function, including peak velocity of systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, fractional area change, RV Tei index, RV longitudinal strain (RVLS), and systolic RV longitudinal strain rate (RVLSR), were obtained by use of speckle tracking echocardiography (STE). In addition, SD of the systolic shortening time of the right ventricle for the 6 segments (RV-SD6) was determined with STE. RESULTS Volume overload significantly increased the RV end-diastolic pressure, compared with the baseline value. Echocardiographic indices of RV function, except for septal RVLSR, were significantly enhanced by volume overload. In contrast, RV-SD6 did not change with volume overload. Although echocardiographic indices of RV function, except for septal RVLSR, were correlated with RV end-diastolic pressure, RV-SD6 was not correlated. CONCLUSIONS AND CLINICAL RELEVANCE Echocardiographic indices of RV function, including RVLS and RVLSR, were affected by acute short-term volume overload. Therefore, results for assessment of RV function by use of STE in dogs with clinical conditions associated with right-sided chronic volume overload, such as tricuspid and pulmonic regurgitation, should be interpreted with caution.

Échographie pulmonaire en dialyse

Profound deficit of the body fluid composition regulation system is present at the end stage kidney disease, leading to the increase the risk of acute or chronic volume overload, which impacts the morbidity and mortality in these patients. Pulmonary ultrasound by its ability to estimate extrapulmonary water at an infraclinical stage has helped to make progress in this area. Line B is the element of fundamental semiology that reflects the presence of water in the pulmonary alveoli. The alteration of left ventricular function and the increase of pulmonary capillary permeability are the determining factors in the genesis of subclinical pulmonary congestion and are positively correlated with B-lines. Because of its non-invasive nature, its ease of use, its intra- and interoperability reproducibility and its ease of learning, nephrologists can be efficiently and quickly trained to use it to measure pulmonary congestion. Recent data have shown an epidemiological association between B-lines and mortality in end stage kidney disease patients. The causal role of subclinical pulmonary congestion assessed by these B lines in the genesis of detrimental events is being evaluated by a randomized, multicentre, open-label European clinical trial (Lung water by ultra-sound guided treatment [LUST] trial). The clinical usefulness of pulmonary ultrasound in the management of subclinical pulmonary congestion in patients with end stage kidney disease remains to be determined, but it could be considered from now as an additional tool to improve the management of this congestion, possibly by complementing bioimpedancemetry data.

Arterial stiffness in end-stage renal disease—pathogenesis, clinical epidemiology, and therapeutic potentials

Arterial stiffness is an important risk factor for cardiovascular morbidity and mortality in patients with end-stage renal disease (ESRD). Arterial stiffness aggravates cardiovascular risk via multiple pathways, such as augmentation of aortic systolic pressure, subendocardial hypoperfusion, and excess pulsatile energy transmission from macro- to microcirculation. Pathogenesis of the arteriosclerotic process in ESRD is complex and not yet fully understood. Several factors unique to ESRD, such as mineral metabolism disturbances, vascular calcifications, formation of advanced glycation end-products, and acute and chronic volume overload, are proposed to play a particular role in the progression of arteriosclerosis in ESRD. As these and other mechanistic pathways of arterial stiffening in ESRD are elucidated, there is hope that this knowledge will be translated into novel therapeutic interventions targeting arterial stiffness. In the meantime, blood pressure (BP) lowering via strict volume control and appropriate use of antihypertensive drugs is a fundamental step in reversing accelerated arterial stiffening and modifying the cardiovascular risk profile of ESRD patients. In this article, we review the pathogenesis, clinical epidemiology, and therapies targeting arterial stiffness in ESRD, discussing recent advances and high-priority goals of future research in these important areas.

Abstract TP192: Change in Cerebral Blood Flow Velocities Before and After Diuresis in an Outpatient Heart Failure Clinic

Background: Cognitive deficits have been described in individuals with heart failure (HF), with worsening at the time of acute decompensation and volume overload. We evaluated transcranial doppler cerebral blood flow velocities (CBFVs), as an index of cerebral perfusion, before and after IV diuresis, in an outpatient HF clinic, to explore mechanisms of cognitive dysfunction during HF decompensation, and to test if velocities improved after diuresis. Methods: In an ongoing study of cognitive evaluation in an outpatient HF diuresis clinic, patients had CBFVs measured before diuresis, and again after completion of daily dosing of IV diuresis (1-7 days later, whenever they were considered to be euvolemic and no longer needing diuresis). Clinical signs and symptoms of volume overload including pulmonary edema, peripheral edema, and ascites were tracked by clinic staff. CBFVs (cm/sec) in several intracranial vessels were compared within individuals, with paired t-tests, before and after completion of the IV diuresis treatment. In linear regression models, we evaluated improvement in volume status in association with change in CBFVs. Results: A total of 21 individuals completed CBFVs before and after diuresis. In all vessels tested (table), CBFVs decreased after diuresis, and in many cases, went from a high to a normal value. Although numbers were small, those individuals with the most improvement in their volume status had more improvement in CBFVs in several but not all vessels. For several vessels, improvement in CBFV was significantly associated with improvement on some cognitive tests. Conclusions: CBFVs are frequently elevated in individuals with decompensated heart failure, with return to a normal range after diuresis. Further evaluation of CBFV as a potential mediator of cognitive dysfunction in HF is warranted.

Monoamine oxidase A inhibition protects the myocardium after experimental acute volume overload.

Objective:The molecular pathway leading to myocardial cellular destruction after acute volume overload (AVO) may include monoamine oxidases. The aim of the present study was to investigate whether moclobemide (Mo), a monoamine oxidase inhibitor, protects the myocardium after AVO.Methods:Sixty syngeneic Fischer rats underwent surgical abdominal aortocaval fistula to induce AVO. Eighteen rats were treated with Mo 10 mg/kg/day and were compared with 42 untreated rats with AVO without treatment. Myocardial recovery was analyzed using quantitative reverse transcription polymerase chain reaction for hypoxia-inducible factor 1-alpha, inducible nitric oxide synthase, interleukin 6, E-selectin, atrial natriuretic peptide (ANP), brain natriuretic peptide, vascular endothelial growth factor-alpha, matrix metalloproteinase 9, chitinase 3-like protein (YKL-40), and transforming growth factor-beta.Results:After 3 days, the relative number of ischemic intramyocardial arteries in the left ventricle was lower in AVO treated with Mo than in without [0.04 (0.02–0.07) vs. 0.09 (0.07–0.14), point score unit]. After 1 day, ANP was lower in AVO treated with Mo than in without [0.95 (0.37–1.84) vs. 2.40 (1.33–3.09), fold changes from the baseline (FC), p=0.044], whereas after 1 and 3 days, YKL-40 was higher in AVO treated with Mo than in without [22.66 (14.05–28.83) vs. 10.06 (6.23–15.02), FC, p=0.006 and 6.03 (4.72–7.18) vs. 3.70 (2.62–5.35), FC, p=0.025].Conclusion:Mo decreases intramyocardial arterial ischemia of the left ventricle after AVO while increases YKL-40, reflecting cellular protection during early cardiac remodeling. In the future, adding Mo may be a simple means for myocardial protection after AVO. (Anatol J Cardiol 2019; 21: 39-45)

Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

Surgical Acute Volume-Overload Impacts Early on Myocardium - An Experimental Study.

Acute volume-overload (AVO) predisposes to cardiac failure. Global cardiac injury may ensue after acute right-sided distension of the heart due to AVO. We experimentally investigated whether surgical AVO impacts early on the myocardium and some markers of injury. Thirty-four syngeneic Fisher rats underwent surgical abdominal aortocaval fistula to induce AVO. The hearts were procured for regional and quantitative histology after one and three days. Gene expressions for atrial natriuretic peptide (ANP), matrix metalloprotease 9 (MMP9), transforming growth factor β (TGFβ) and YKL40 were investigated for myocardial injury. The relative number of ischemic intramyocardial arteries were abundant in the septum of the hearts with AVO compared with controls at day 1 and 3 [0.16 ± 0.02 vs. 0.02 ± 0.01, point score unit (PSU), p = 0.002 and 0.14 ± 0.02 vs. 0.02 ± 0.01, PSU, p = 0.009, respectively] followed by similar changes in the left ventricle at day 3 (0.11 ± 0.02 vs. 0.04 ± 0.01, PSU, p = 0.007). Indicating early myocardial injury, ANP (p = 0.019) was increased in AVO hearts as compared with controls at day 1, as expected. More interestingly, MMP9 (p = 0.003 and p = 0.006), TGFβ (p = 0.002 and p = 0.004) and YKL40 (p = 0.001 and p = 0.003) expressions were significantly increased at day 1 and 3, along with macrophage infiltration into the myocardium supporting the role of factors produced by alternatively activated macrophages in the pathogenesis of AVO-induced pathophysiology in the heart. Surgical AVO induces an early ischemic myocardial response observed in the intramyocardial arteries. Early expression of key parameters of cardiac remodeling suggest for the onset of early cardiac failure after AVO.

The Impact of Hemodynamic Transesophageal Echocardiography on the Use of Continuous Renal Replacement Therapy in Trauma

Post-traumatic fluid management is a widely debated topic. No best-practice consensus exists. Adverse outcomes such as acute kidney injury or volume overload are common. Continuous renal replacement therapy (CRRT) is an adjunct therapy for severe acute renal failure and volume overload, but is costly and not without risk. Hemodynamic transesophageal echocardiography (hTEE) is widely accepted as a reliable way to monitor volume status of intensive care unit (ICU) patients. Although data exist evaluating hTEE and CRRT independently, there is a lack of research mutually inclusive of the two. We hypothesized that the use of hTEE is associated with less need for CRRT. Retrospective review of a level I trauma center from 2009 to 2015 identified patients that required CRRT. In 2013, we implemented a protocol using hTEE in trauma patients with significant resuscitation needs. We compared CRRT use before and after implementation of the protocol (pre- and post-hTEE). Multivariate analysis using two sample t tests and χ2 test of the odds ratio (O.R.) was completed on variables such as injury severity score (ISS), acute kidney injury network (AKIN), days of CRRT, ICU length of stay (LOS), and hospital LOS. A total of 5037 and 6699 trauma patients were evaluated in the pre- and post-hTEE groups, respectively. Mean ISS was 22 and 28 for pre- and post-hTEE, respectively (P value 0.19). Mean AKIN was 2.7 for both groups. Mean days on CRRT was eight before hTEE and seven after hTEE (P value 0.7); 23 patients required CRRT pre-hTEE, and 15 required CRRT post-hTEE (P value 0.01 O.R. 2.4). Given, the odds of CRRT pre-hTEE are more than twice that of CRRT post-hTEE; we conclude that the use of hTEE is associated with a reduction of CRRT.

Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction

ObjectivesIn this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BackgroundLimited data are available on biomarker profiles in acute HFmrEF. MethodsA panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). ResultsHemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction <0.05). ConclusionsBiomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

New Parameter Derived from Three-Dimensional Speckle-Tracking Echocardiography for the Estimation of Left Ventricular Filling Pressure in Nondilated Hearts

E/e' is clinically useful for the noninvasive assessment of left ventricular (LV) filling pressure. However, its use in some conditions is controversial, and angle dependence of the Doppler measurement and preload dependence of mitral e' in nondilated hearts represent major problems. The ratio of early filling rate derived from the time derivative of LV volume to early diastolic strain rate (FRe/SRe), similar to E/e', by three-dimensional (3D) speckle-tracking echocardiography has the potential to address such limitations. This study investigated whether FRe/SRe could estimate acute changes in LV filling pressure using the models of volume overload and myocardial ischemia in the nondilated heart. In 25 dogs, hemodynamic conditions were varied by acute volume overload and coronary occlusion. FRe and SRe were obtained from the same beat and automatically analyzed by the 3D speckle-tracking method, and global SRe was measured from longitudinal (L-SRe), circumferential (C-SRe), and area strain rate (A-SRe). E/e' was measured by two-dimensional echocardiography. LV pressure was derived from a micromanometer catheter and recorded simultaneously with the acquisition of the 3D images. Mitral e' and L-SRe varied by changes in preload, whereas C-SRe and A-SRe did not. C-SRe and A-SRe were more strongly correlated with the time constant of LV relaxation than mitral e' and L-SRe. FRe/C-SRe and FRe/A-SRe had relatively high correlations with LV preatrial contraction (pre-A) pressure and end-diastolic pressure, but E/e' and FRe/L-SRe did not. Receiver operating characteristics curve analysis showed that FRe/C-SRe and FRe/A-SRe had larger areas under the curve for the estimation of increased LVfilling pressure. The novel parameter FRe/SRe has potential as a surrogate marker of LV filling pressure. Especially in nondilated hearts, FRe/C-SRe and FRe/A-SRe may be useful to more accurately predict LV filling pressure than E/e', although their applicability in dilated hearts requires further investigation.

Concomitant insertion of peritoneal dialysis catheter and ventriculoperitoneal shunt in children: a report of two cases

The aim of this study was to know and validate whether the use of ventriculoperitoneal shunt (VPS) and peritoneal dialysis catheter (PDC) is a safe and acceptable option in children requiring PD and VPS. A case of myelomeningocele with accompanied paraplegia and hydrocephalus was treated surgically in the neonatal period with placement of VPS. Later the child developed a neurogenic bladder with recurrent cystitis, which culminated into severe bilateral ureterohydronephrosis and progressive chronic renal disease. In a second case, a boy with an immaculate past history, admitted in a local hospital for meningitis complicated by hydrocephalus, necessitating the insertion of VPS, was treated. During the course of his illness, the child developed acute renal failure, volume overload, and severe hypertension and ended up in our pediatric ICU. We experienced two cases in our artificial kidney unit with concomitant insertion of VPS and PDC with an excellent outcome. On the basis of the outcomes of our patients as well as results from other centers, we conclude that the concurrent use of a VPS and PDC is a safe and acceptable option in child requiring PD and VPS.

The Electrophysiologic Effects of Acute Mitral Regurgitation in a Canine Model

Atrial fibrillation (AF) occurs in 30% of patients with mitral regurgitation referred for surgical intervention. However, the underlying mechanisms in this population are poorly understood. This study examined the effects of acute left atrial volume overload on atrial electrophysiology and the inducibility of AF. Ten canines underwent insertion of an atrioventricular shunt between the left ventricle and left atrium. Shunt and aortic flows were calculated, and the shunt was titrated to a shunt fraction to 40% to 50% of cardiac output. An epicardial plaque with 250 bipolar electrodes was used to determine activation and refractory periods. Biatrial pressures and volumes, conduction times, and atrial fibrillation inducibility were recorded. Data were collected at baseline and 20 minutes after shunt opening and closure. Mean shunt flow was 1.3 ± 0.5 L/min with a shunt fraction of 43% ± 6% simulating moderate to severe mitral regurgitation. Compared with baseline, left atrial volumes and maximum pressures increased by 27% and 29%, respectively, after shunt opening. Biatrial effective refractory periods did not change significantly after shunt opening or closure. Conduction times increased by 9% with shunt opening and returned to baseline after closure. AF duration or inducibility did not change with shunt opening. This canine model of mitral regurgitation demonstrated that acute left atrial volume overload did not increase the inducibility of atrial arrhythmias in contrast with experimental and clinical findings of chronic left atrial volume overload. This suggests that the substrates for AF in patients with mitral regurgitation are a result of chronic remodeling.

Serum Potassium Levels and Outcome in Acute Heart Failure (Data from the PROTECT and COACH Trials)

Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (<3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (>5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 ± 11years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 ± 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p= 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p= 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment.

Congestive Adenopathy

Endosonography has improved our ability to reach thoracic lymph nodes and to diagnose pathologic conditions with nodal involvement and has lowered the threshold for biopsy. The purpose of this study was to avoid unnecessary procedures, it is important to recognize benign adenopathy. Congestive heart failure (CHF) is both common and a common cause of adenopathy. The purpose of this study was to study the association between CHF and adenopathy and to describe the typical presentation of congestive adenopathy. We performed a retrospective correlation of computed tomographic (CT) and laboratory findings for patients admitted to hospital with a diagnosis of CHF. Of 500 patients admitted with a diagnosis of CHF, 215 appeared to have CT scans of the chest, and not to have a potentially confounding etiology of adenopathy. The incidence of adenopathy in this study group was 68%. Pulmonary edema on CT and pleural effusion were both significantly associated with adenopathy (P<0.01 for both). The pattern of congestive adenopathy was one of enlargement of several mediastinal nodes and less likely to involve hilar nodes and single stations in isolation. Congestive adenopathy is common in patients with evidence for acute volume overload. The pattern of presentation should allow clinicians to recognize congestive adenopathy and to separate it from other adenopathy for which biopsy might be appropriate.

Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs.

OBJECTIVE To elucidate the relationship between acute volume overload and left atrial phasic function in healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized. A Swan-Ganz catheter was placed to measure mean pulmonary capillary wedge pressure (PCWP). Cardiac preload was increased by IV infusion with lactated Ringer solution at 150 mL/kg/h for 90 minutes. Transthoracic echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after volume loading began. At each echocardiographic assessment point, apical 4-chamber images were recorded and analyzed to derive time-left atrial area curves. Left atrial total (for reservoir function), passive (for conduit function), and active (for booster-pump function) fractional area changes were calculated from the curves. RESULTS Volume overload resulted in a significant increase from baseline in PCWP from 15 to 90 minutes after volume loading began. All fractional area changes at 15 to 90 minutes were significantly increased from baseline. In multiple regression analysis, quadratic regression models were better fitted to the relationships between PCWP and each of the total and active fractional area changes than were linear regression models. A linear regression model was better fitted to the relationship between PCWP and passive fractional area change. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that left atrial phasic function assessed on the basis of left atrial phasic areas was enhanced during experimental cardiac volume loading in healthy dogs. The effect of volume load should be considered when evaluating left atrial phasic function by indices derived from left atrial phasic sizes.

Anesthesia for pregnant women with pulmonary hypertension.

Purpose of review is to summarize and highlight recent advances in the management of pregnant patients with pulmonary hypertension. Despite recent advances in the therapy of pulmonary hypertension, prognosis for pregnant patients with pulmonary hypertension remains poor with high maternal mortality. Pregnancy is still considered contraindicated in these patients. If pregnancy occurs, referral to a tertiary hospital and a multidisciplinary approach ensure the best possible outcome. All pregnant patients with pulmonary hypertension should be counseled for a termination of pregnancy. If the patient wants to continue the pregnancy despite strong recommendations for therapeutic interruption, specific pulmonary hypertension therapy has to be initiated, adjusted, and/or augmented. A close clinical follow-up of the mother throughout the entire pregnancy is of utmost importance. Elective caesarean section in week 34-36 is recommended as preferred mode of delivery, preferentially under epidural or low-dose combined spinal-epidural anesthesia. Because of an acute increase in pulmonary vascular resistance and delivery-associated acute volume overload, the immediate postpartum period carries the highest risk for acute right ventricular failure necessitating close monitoring and treatment on an ICU. Anesthesiologists involved in the management of pregnant patients with pulmonary hypertension must have detailed knowledge of pathophysiological alterations in pregnancy and during birth, cardiac (patho)physiology, cardiovascular and obstetric pharmacology, hemodynamic monitoring, and echocardiography. Both regional and general anesthesia have typical adverse effects that can severely jeopardize the cardiovascular system in patients with pulmonary hypertension, and should therefore be anticipated/prevented/rapidly treated by the attending anesthesiologist.

Transcatheter Mitral Valve Repair, MitraClip, in a Nonagenarian Patient with Acute Regurgitation

Acute volume overload on the left ventricle causes pulmonary congestion and low cardiac output. If this volume overload is not tolerated, despite full drug treatment, emergency surgery should be performed1. These patients, however, face high surgical risk inherent in the procedure, which can become prohibitive in the presence of old age and comorbidities2. In such circumstances, non-surgical treatment options, such as transcatheter mitral repair, appear as less invasive and lower risk treatment alternatives2. This report describes the case of a nonagenarian patient with acute MR and high surgical risk who underwent successful MitraClip transcatheter implant.

Abstract 17940: PDEV Inhibition + BNP Administration Enhanced the Cardiac but not the Renal Response to Acute Volume Overload in Human Preclinical Diastolic Dysfunction as Compared to PDEV Inhibition Alone

Background: Preclinical diastolic dysfunction (PDD) is defined as subjects with normal systolic function, moderate or severe diastolic dysfunction determined by Doppler criteria but with no symptoms of heart failure (HF). We have previously demonstrated that an impaired cardiorenal endocrine response to stress by acute volume loading (AVL) exists in PDD and that is corrected by acute administration of sq B-type natriuretic peptide (BNP). Type V phosphodiesterase (PDEV) metabolizes cGMP, second messenger of BNP. The objective of the current study is to determine if the combination of PDEV inhibitor (PDEVI) and BNP will result in a greater enhancement of the cardiorenal response to AVL as compared to PDEVI alone in PDD. Methods: Randomized double-blind single placebo-controlled cross-over study in 20 PSD subjects. We determined cardiorenal effects of PDEVI with Tadalafil (T) 5 mg alone and in combination with acute sq BNP (Nesiritide 10 μg/Kg), in response to AVL (normal saline 0.25 ml/kg/min for 1 hour). Each subject had 2 study visits, separated by at least 1 week. At each visit, echocardiogram and renal clearance studies with iothalmate and PAH to measure GFR and renal plasma flow (RPF) were done before and after AVL. Each patient was randomized to receive T at both visits and either placebo or sq-BNP one visit and crossover to the other on the next visit. Results: T+BNP resulted in smaller LA volume index (-4±10 vs 3±7 ml/m 2 , p&lt; 0.05) and lower right ventricular systolic pressure (-4±3 vs 2±6 mmHg, p&lt; 0.05) in response to AVL as compared to T alone. Moreover, T+ BNP resulted in a significant reduction of plasma ANP and LV end-systolic volume in response to AVL while T alone did not. However, the combination to T+BNP did not enhance the renal response to AVL as compared to T alone. Both the change in urine flow (1.7±5 vs 2.4±5 ml/min, p&gt; 0.05) and sodium excretion (129±200 vs 124±270 mEq/min, p&gt;0.05) in response to AVL were similar between T+BNP and T alone. Conclusion: In PDD, the combination of PDEVI and BNP reduced LV filling pressure in response to AVL as compared to PDEVI alone. However, it did not enhance the renal response to AVL. This suggests a differential cardiac versus renal response to the maximization of cGMP system with PDEVI and BNP.

Hypertension in African Americans with heart failure: progression from hypertrophy to dilatation; perhaps not.

Concentric hypertrophy is thought to transition to left ventricular (LV) dilatation and systolic failure in the presence of long standing hypertension (HTN). Whether or not this transition routinely occurs in humans is unknown. We consecutively enrolled African American patients hospitalized for acute decompensated volume overload heart failure (HF) in this retrospective study. All patients had a history of HTN and absence of obstructive coronary disease. Patients were divided into those with normal left ventricular ejection fraction (LVEF) and reduced LVEF. LV dimensions were measured according to standard ASE recommendations. LV mass was calculated using the ASE formula with Devereux correction. Patients with normal LVEF HF were significantly older, female and had a longer duration of HTN with higher systolic blood pressure on admission. LV wall thickness was similarly elevated in both groups. LV mass was elevated in both groups however was significantly greater in the reduced LVEF HF group compared to the normal LVEF HF group. Furthermore, gender was an independent predictor for LV wall thickness in normal LVEF HF group. In African American patients with HF our study questions the paradigm that concentric hypertrophy transitions to LV dilatation and systolic failure in the presence of HTN. Genetics and gender likely play a role in an individual's response to long standing hypertension.