Pulmonary Arterial Saturation Research Articles

Right Atrial Pressure Higher Than The Pulmonary Artery Saturation: An Ominous Finding At Right Heart Catheterization

Right Atrial Pressure Higher Than The Pulmonary Artery Saturation: An Ominous Finding At Right Heart Catheterization

Abstract 17520: Dynamic Intrapulmonary Shunting in the Setting of Amphetamine Use

Description of Case: A 35-year-old female non-smoker with ADHD on amphetamine for the past 3 months and family history of hereditary hemorrhagic telangiectasia (HHT) presented with significant exertional dyspnea for 1 week. She was hypoxic to 82% while walking, with normal oxygen saturation at rest. Transthoracic echocardiogram with agitated saline revealed extracardiac right-to-left shunting with exercise and Valsalva. This was confirmed by dobutamine stress echocardiogram with agitated saline (Figure 1A). Transesophageal echocardiogram with agitated saline (Figure 1B) revealed no shunt through the foramen ovale, but it demonstrated bubbles entering from the left upper pulmonary vein, suggestive of an extracardiac shunt from a pulmonary arteriovenous malformation (AVM). Right heart catheterization and pulmonary angiogram revealed normal pressures, and no pulmonary abnormalities with normal pulmonary venous return. Supine right heart catheterization with exercise revealed normal pressures, although the initial pulmonary artery (PA) saturation was 28%; repeat PA saturation one minute later was 48%. Arterial saturation was 95%. Pulmonary function testing, ventilation perfusion scan, high-resolution CT chest, and coronary CT angiogram were unremarkable. The patient was instructed to avoid all stimulants, and to take a non-hormonal contraceptive. At her 3-month follow-up, she reported significant improvement in her symptoms. She underwent a 6-minute walk test, and her lowest oxygen saturation was 88%. Discussion: This patient presented with exertional hypoxia, normal saturations at rest, evidence of an extracardiac shunt only with exertion and absence of clear sources of the shunt on imaging. With her family history of HHT, this is suggestive of a small pulmonary AVM that opened by elevated PA pressures, likely triggered by amphetamine use, and its discontinuation led to symptom resolution.

Novel Nebulized Milrinone Formulation for the Treatment of Acute Heart Failure Requiring Inotropic Therapy: A Phase 1 Study

Nonintravenous inotropic-delivery options are needed for patients with inotropic-dependent heart failure (HF) to reduce the costs, infections and thrombotic risks associated with chronic central venous catheters and home infusion services. We developed a novel, concentrated formulation of nebulized milrinone for inhalation and evaluated the feasibility, safety and pharmacokinetic profile in a prospective, single-arm, phase I clinical trial. We enrolled 10 patients with stage D HF requiring inotropic therapy during a hospital admission for acute HF. Milrinone 60 mg/4 mL was inhaled via nebulization 3 times daily for 48 hours. The coprimary outcomes were adverse events and pharmacokinetic profiles of inhaled milrinone. Acute changes in hemodynamic parameters were secondary outcomes. A concentrated nebulized milrinone formulation was well tolerated, without hypotensive events, arrhythmias or inhalation-related adverse events requiring discontinuation. Nebulized milrinone produced serum concentrations in the goal therapeutic range with a median plasma milrinone trough concentration of 39 (17-66) ng/mL and a median peak concentration of 207 (134-293) ng/mL. There were no serious adverse events. From baseline to 24 hours, mean pulmonary artery saturation increased (60% ± 7%-65 ± 5%; P = 0.001), and mean cardiac index increased (2.0 ± 0.5 mL/min/1.73m2-2.5 ± 0.1 mL/min/1.73m2; P = 0.001) with nebulized milrinone. In a proof-of-concept study, a concentrated, nebulized milrinone formulation for inhalation was safe and produced therapeutic serum milrinone concentrations. Nebulized milrinone was associated with improved hemodynamic parameters of cardiac output in a population with advanced HF. These promising results require further investigation in a longer-term trial in patients with inotrope-dependent advanced HF.

Prognostic Value of Respiratory Variation in Right Atrial Pressure in Patients With Precapillary Pulmonary Hypertension

Precapillary pulmonary hypertension (PH) is characterized by elevated mean pulmonary artery pressure from increased pulmonary vascular resistance (PVR). Lack of respiratory variation in right atrial pressure (RAP) can be viewed as a surrogate for severe PH and inability of the right ventricle (RV) to tolerate preload augmentation during inspiration. Is the lack of respiratory variation in RAP predictive of RV dysfunction and worse clinical outcomes in precapillary PH? We retrospectively reviewed RAP tracings of patients with precapillary PH who underwent right heart catheterization. Patients with respiratory variation in RAP (end expiratory - end inspiratory) ≤2 mmHg were considered to have effectively no meaningful variation in RAP. Lack of respiratory variation in RAP was associated with lower cardiac index by indirect Fick (2.34±0.09 vs. 2.76±0.1 L/min/m2, p=0.001), lower pulmonary artery saturation (60±1.02% vs 64±1.15%, p=0.007), higher PVR (8.9±0.44 vs 6.1±0.49 Wood units, p<0.0001), RV dysfunction on echocardiography (87.3% vs 38.8%, p<0.0001), higher proBNP (2163±2997 vs 633±402 ng/ml, p<0.0001), and more hospitalizations within 1 year for RV failure (65.4% vs 29.6%, p<0.0001). There was also a trend toward higher mortality at 1 year in patients with no respiratory variation in RAP (25.4% vs 11.1%, p=0.06). Lack of respiratory variation in RAP is associated with poor clinical outcomes, adverse hemodynamic parameters, and RV dysfunction in patients with precapillary PH. Larger studies are needed to further evaluate its utility in prognosis and potential risk stratification in patients with precapillary PH.

CORRELATION OF QUANTITATIVE BLOOD VOLUME ANALYSES FROM CT IMAGING WITH HEMODYNAMICS IN PATIENTS WITH PULMONARY HYPERTENSION

CORRELATION OF QUANTITATIVE BLOOD VOLUME ANALYSES FROM CT IMAGING WITH HEMODYNAMICS IN PATIENTS WITH PULMONARY HYPERTENSION

Riding The Storm: Utilizing VA-ECMO As A Bridge To Recovery In A Patient With Fulminant Necrotizing Eosinophilic Myocarditis

<h3>Background</h3> Fulminant necrotizing eosinophilic myocarditis (FNEM) is a rare form of eosinophilic myocarditis characterized by new onset heart failure often requiring inotropic and mechanical circulatory support (MCS). Early endomyocardial biopsy (EMB) and prompt immunosuppressive therapy can prevent further decompensation and death, especially in patients presenting with cardiogenic shock. <h3>Case presentation</h3> A 52-year-old female with prior history of mild asthma presented with dyspnea and chest tightness. Vital signs were significant for temperature of 100.9 F, pulse of 140 in sinus rhythm and blood pressure of 89/70. Physical exam was remarkable for crackles at the mid-lower lung fields bilaterally. Baseline EKG showed sinus tachycardia, septal Q waves with ST elevation in V1, V2 and diffuse subtle ST-depressions in the other leads (Figure 1A). Troponin T was elevated to 3.25 ng/ml, pro-BNP was 23,424 pg/ml, CRP was 26.2mg/dl and ESR to 116mm/hour . A 2D echo showed severely reduced left ventricular systolic function with left ventricular ejection fraction (LVEF) of 25-29%, normal left ventricular dimensions, and mildly reduced right ventricular systolic function. Emergent coronary angiography demonstrated no significant coronary artery disease. Right heart catheterization showed a pulmonary artery saturation of 55%, fick cardiac index 1.72, systemic vascular resistance (SVR) of 2128 dynes and elevated bi-ventricular filling pressure (mean right atrial pressure; 23, mean pulmonary capillary wedge pressure; 30mmHg). An endomyocardial biopsy was performed which was consistent with necrotizing eosinophilic myocarditis (Figure 1B). The patient was started on pulse dose steroids. During the first 24 hours she continued to be hemodynamically unstable and required two inotropes to maintain adequate end-organ perfusion. She was placed on VA-ECMO simultaneous with an IABP for left ventricular unloading. Eventually, after being on mechanical support for 7 days, her hemodynamic status improved and her biventricular function completely normalized by day 9. Mechanical and inotropic support was successfully weaned. Patient was discharged on day 23 with a goal to continue a long steroid taper for 6 months. <h3>Conclusion</h3> FNEM is an extremely rare and life threatening pathology that often presents with cardiogenic shock. It is eminently treatable if recognized early during its course. Early EMB should be performed to guide decisions for immunosuppressive therapy. We present a case of FNEM with extremis shock successfully managed with early MCS as bridge-to-recovery.

Abstract 12078: Pre-Glenn Aorto-Pulmonary Collaterals and Its Impact on Outcomes in Single Ventricle Patients

Introduction: In single-ventricle patients undergoing bi-directional Glenn (BDG), 36-59% have angiographically detectable aorto-pulmonary collateral (APC) flow. However, predictors, hemodynamic and clinical outcomes are unknown. Hypothesis: We hypothesize that (a) shunt type, hemodynamic findings at the pre-Glenn catheterization predict pre-BDG APC burden and (b) APC burden at BDG catheterization may predict post BDG death/transplantation, pulmonary artery (PA) or APC intervention. Methods: Retrospective cohort study of patients following Norwood Procedure for single ventricle anatomy. Covariates included demographics; clinical and hemodynamic at Pre-BDG catheterization. APC burden at pre-BDG catheterization was assessed dichotomously by a single reader (moderate/severe vs. none/mild). Logistic regression was used to identify predictors of APC burden and Cox regression for time to clinical outcomes. Results: Among 104 patients, 89.4% (n=93/104) underwent pre-BDG catherization, of which 55% (n=51/93) had APC intervention and 91% (n=85/93) progressed to BDG. Post-BDG, 60% (n=51/85) had no/mild and 40% (n=34/85) had moderate/severe APC burden. Within 36 months, APC intervention occurred in 74% (n=69/63) with no difference between groups (84% vs. 79%, Logrank 0.75). Predictors of APC burden were male sex (OR 3.59; 95% CI 1.18-10.98), older age at BDG (1.02 per year; 1.01-1.04), PA saturations (1.80;1.18-2.75), and Qp:Qs ratio (OR 1.23 per 0.10 unit increase;1.08-1.41). APC burden is not predictive of death/transplantation or future APC intervention but may show a trend towards future PA intervention (HR 2.11, 95% CI 0.98-4.52, p=0.056)(Figure 1). Sano shunt is a predictor of APC intervention following BDG (HR 2.07, 95%CI 1.09-3.90, p=0.03). Conclusions: Moderate or severe APC burden was present in 40% after stage I Norwood and QP:QS is a strong predictor for APC burden; patients with moderate/severe APC’s may be at higher risk of PA interventions.

Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results.

Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656.

Pulmonary Artery Catheter Usage and Mortality in Cardiogenic Shock

Mortality in cardiogenic shock (CS) remains prohibitively high despite recent advances in treatment. The extent of clinical benefit of the use of pulmonary artery catheters (PACs) in CS patients is still unclear. We hypothesize that the comprehensive assessment of PAC data is associated with reduced risk of in-hospital mortality in CS patients. 1,414 all-cause CS patients from the Cardiogenic Shock Working Group Registry, a national multicenter retrospective CS registry, were classified according to the Society for Cardiovascular Angiography and Intervention (SCAI) CS stages and evaluated for PAC use. PAC use was quantified by the presence of pulmonary artery saturation, pulmonary artery pressures and wedge pressure. We compared patients without any of these measurements (No PAC data), patients with at least one (Some PAC data) and patients with all these parameters and right atrial pressure (Complete PAC data). PAC usage was analyzed for association with in-hospital mortality in a multivariate logistic regression model. Of the total cohort of 1414 patients, 267 (18.88%) had no recorded PAC data, 549 (38.83%) had partially recorded PAC data, and 598 (42.29%) had complete PAC data. The majority of SCAI stage B (n=43, 93.5%) and C (n=132, 50.19%) had complete PAC data while the majority of SCAI stages D (n=361, 47.63%) and E (n=90, 42.45%) had some PAC data. After adjusting for institution in the total cohort, patients with complete PAC data had almost half the risk of mortality compared to those with no PAC data (OR 95%CI: 0.586, 0.418-0.822) and those with partial PAC data (OR 95%CI: 0.602, 0.467-0.813). The differences in mortality by PAC usage in the overall and SCAI stage cohorts are summarized in the figure below. These data suggest that using a PAC in CS patients, especially those in more critical condition, may decrease their risk of in-hospital mortality. This benefit could potentially be explained by the information provided by the PAC in developing a more appropriate treatment plan.

Precapillary pulmonary gas exchange is similar for oxygen and inert gases.

Precapillary gas exchange for oxygen has been documented in both humans and animals. It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET). We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1cm proximal to the wedge position) and systemic artery. Some 12-19% of pulmonary gas exchange occurred within small (1.7mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane. Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1cm proximal to the wedge position (using a 5-F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F=(P-D)/(P-A). The lowest solubility inert gases, sulphur hexafluoride (SF6 ) and ethane were used because, with higher solubility gases, the P-A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n=12) with oxygen (O2 ) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P=88.6±18.1%; P=0.03) and ethane (D/P=90.6±16.0%; P=0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1±6.8% vs. 69.0±4.9%; P=0.03). Fractional precapillary gas exchange was similar for SF6 , ethane and O2 (0.12±0.19, 0.12±0.20 and 0.19±0.26, respectively; P=0.54). Under these experimental conditions, 12-19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases.

Cardiovascular Parameters in a Swine Model of Normobaric Hypoxia Treated With 5-Hydroxymethyl-2-Furfural (5-HMF).

Introduction:The consequences of low partial pressure of O2 include low arterial O2 saturations (SaO2), low blood O2 content (CaO2), elevated mean pulmonary artery pressure (PAP), and decreased O2 consumption VO2. 5-hydroxymethyl-2-furfural (5-HMF) binds to the N-terminal valine of hemoglobin (HgB) and increases its affinity to O2. We used an instrumented, sedated swine model to study the effect of 5-HMF on cardiovascular parameters during exposure to acute normobaric hypoxia (NH).MethodsTwenty-three sedated and instrumented swine were randomly assigned to one of three treatment groups and received equal volume of normal saline (VEH), 20 mg/kg 5-HMF (5-HMF-20) or 40 mg/kg 5-HMF (5-HMF-40). Animals then breathed 10% FiO2 for 120 min. Parameters recorded were Cardiac Output (CO), Mean Arterial Blood Pressure (MAP), Heart Rate (HR), Mean Pulmonary Artery Pressure (PAP), SaO2 and saturation of mixed venous blood (SvO2). The P50 was measured at fixed time intervals prior to and during NH.Results5-HMF decreased P50. In the first 30 min of NH, treatment with 5-HMF-20 and 5-HMF-40 resulted in a (1) significantly smaller decrement in SaO2 and SvO2, (2) significantly lower HR and CO, and (3) smaller increase in PAP compared to VEH. In the 120 min of NH there was a trend toward improved mortality with 5-HMF treatment.Conclusion5-HMF treatment decreased P50, improved SaO2, and mitigated increases in PAP in this swine model of NH.

Sildenafil for This Heart Failure With a Preserved Ejection Fraction? Diastolic Dysfunction and Gerbode Defect Induced Combined Precapillary and Postcapillary Pulmonary Hypertension

SESSION TITLE: Pulmonary Vascular Disease SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Tuesday, October 31, 2017 at 04:30 PM - 05:30 PM INTRODUCTION: A Gerbode defect is a ventricular septal defect (VSD) communicating directly between the left ventricle (LV) and right atrium (RA). The shunt can be either congenital or acquired. Acquired cases are secondary to cardiothoracic surgeries. CASE PRESENTATION: A 66 year-old woman was hospitalized with acute on chronic diastolic heart failure. She had a history of mitral valve papillary muscle rupture replaced with a bioprosthesis and bypass for coronary artery disease. BP was 99/69 (MAP 70), HR 70 bpm, with normoxia at rest and with exertion. Exam showed an internal jugular vein with prominent v-wave, loud holosystolic murmur, right sided heave and 3+ edema. Lab results showed a hemoglobin of 17 mg/dL, creatinine 1.6 mg/dL and BNP 2584 pg/mL. Surface echocardiogram revealed preserved LV function, markedly dilated right ventricle with flattening of the intraventricular septum, severe tricuspid regurgitation (TR), tricuspid annular plane systolic excursion of 1.6 cm, TR peak velocity jet of 3.3 m/sec and a negative bubble study. A transesophageal echocardiogram showed a large left to right communication in the posterior area of the atria with a high velocity systolic flow. Several right heart catherizations showed persistent oxygen step up at the level of the right atrium. DISCUSSION: The presence of the shunt complicated hemodynamic interpretation. This elevated the pulmonary artery saturation falsely increasing the estimated Fick cardiac output (CO). The low CO by thermodilution and renal insufficiency were consistent with a hemodynamic shock state, and improved with furosemide, sildenafil and midodrine. LV-RA shunt correction was not possible in this patient due to severe RV dysfunction and high peri-operative risk. CONCLUSIONS: Gerbode defect is a VSD communicating directly between the LV and RA. Sildenafil has been shown to reduce pulmonary pressures and improve hemodynamics in patients with combined PH. Longstanding hydrostatic pressure within the pulmonary capillaries with persistent high flow produced venulae damage and vascular remodeling similar to other causes of pulmonary artery hypertension. We describe a patient with combined pre and post-capillary PH with progressive right heart failure successfully treated with medical therapy. Reference #1: Opitz CF, Hoeper MM, Gibbs SR, et al. Pre-capillary, combined, and post-capillary pulmonary hypertension: a pathophysiological continuum. J Am Coll Cardiol 2016 Reference #2: Yuan Shi-Min. A systematic review of acquired left ventricle to right atrium shunt. Hellenic J Cardiol 2015 DISCLOSURE: The following authors have nothing to disclose: Domingo Franco-Palacios, Patrick Kicker, Oksana Shlobin, Qiong Zhao, Mardi Gomberg-Maitland No Product/Research Disclosure Information

Rest and exercise hemodynamic and metabolic findings in active duty soldiers referred for cardiac catheterization to exclude heart disease: Insights from past invasive cardiopulmonary exercise testing using multisensor high fidelity catheters.

This study describes results of iCPET from the past, which used submaximal stress and multisensor high-fidelity catheters to exclude heart disease in a unique population of young adults. There has been resurgence in comprehensive hemodynamic evaluation of complex cardiovascular patients. Although dynamic assessments during cardiac catheterization have become commonplace, there remains limited information regarding left and right heart hemodynamic changes during supine exercise in young adults. The study population was derived from a retrospective review of catheterization records at Brooke Army Medical Center for active duty patients (ages: 19-40 years) in whom hemodynamic waveforms were obtained with multisensor high-fidelity catheters and supine exercise testing (53.1 ± 12.6 watts) and angiography performed to exclude heart disease. We report findings from 41 males and 1 female (ages: 19-40 years) found free of heart disease. Submaximal exercise was associated with ≈ fourfold (P < 0.001) increase in minute ventilation (VE), O2 consumption (VO2 ) and carbon dioxide production (VCO2 ). VE/VCO2 ratio decreased (-16.8 ± 13.9%, P < 0.001) and VE/VCO2 slope was 22.6 ± 0.6 (±SE). Cardiac index (CI) increased with VO2 (ΔCI/ΔVO2 slope = 7.6 ± 2.2). Heart rate increased nearly 10 bpm per 100 mL O2 /min/M2 , whereas, changes in stroke volume were more variable. Pulmonary artery (PA) saturations fell from 77 to 55% (P < 0.001). No change was noted in mean right atrial pressures; PA pressures increased ≈10 mm Hg (P < 0.001). Pulmonary capillary wedge and left ventricular end-diastolic pressures increased ≈2 mm Hg (P < 0.001) but variability noted between individuals. This study provides insight into past practices of invasive cardiopulmonary testing and furthers the understanding of metabolic and hemodynamic changes in a young population during supine submaximal exercise. © 2017 Wiley Periodicals, Inc.

Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes

Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients. Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed. Median survival was 7.8 years in IPAH and 3 years in SSc-PAH (P< .001). Patients with SSc-PAH were older with less severe hemodynamics but lower gas transfer (diffusing capacity for carbon monoxide [Dlco]). Independent prognostic factors were age, SSc, Dlco, pulmonary artery saturation, and stroke volume. After excluding patients with normal or only mildly elevated resistance, there was no difference in the relationship between pulmonary vascular resistance (PVR) and compliance in IPAH and SSc-PAH. The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP= 0.61 sPAP+ 2mmHg). The relationship in SSc-PAH was similar: mPAP= 0.58 sPAP+ 2mmHg (P value for difference with IPAH= 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH. The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.

Acute Effects of Inspiratory Muscle Training on Pulmonary Arterial Pressure,Cardiac Output and Pulmonary Arterial Saturation Derived Oxygen Cost of Breathing

Respiration and respiratory maneuvers affect cardiac output. Inspiratory muscle training (IMT) increases the negative thoracic pressure, which could have an impact on intra-thoracic hemodynamics and thereby influence the cardiac output (CO). The objective of our study was to determine changes in pulmonary arterial (PA) hemodynamics and the CO during IMT in patients with suspected pulmonary hypertension. A new method for measuring the oxygen cost of breathing during IMT was also developed. 22 patients were included in this prospective study. They performed IMT during right heart catheterization. Mixed-venous blood gas analysis was performed before and at the end of IMT to calculate the oxygen cost of breathing. The baseline PA pressure was systolic/diastolic/mean (s/d/m) 41 ± 20/13 ± 20/25 ± 11 mmHg. The CO was 5.3 ± 1.5 l/min. The IMT was set to 2.3 ± 0.6 kPa (23.7 ± 5.7 cmH2O). The PA pressure at the end of IMT was s/d/m 44/10/22 mmHg s/d/m. Though there was a trend towards a lower diastolic pressure, this change was not statistically significant (p=0.06). CO (6.2 ± 1.1 l/min) did not change due to IMT. The mixed-venous hemoglobin oxygen saturation was 71.8 ± 2.3% before IMT, with a significant reduction to 65.8 ± 5.9% (p=0.027) at the end of IMT. IMT as performed in our study neither changed the mean PA pressure nor the CO. Measuring the oxygen cost of breathing is feasible by the method described in our paper.

Features of cutaneous microcirculatory blood flow in patients with pulmonary hypertension of different etiology

Aim: to evaluate features of the functional state of microvascular bed of the skin in patients with pulmonary arterial hypertension associated to congenital cardiac disease (PAH-CCD) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods. In study included 25 patients (41.6±15.8) with PAH-CCD, 25 patients (48.8±14.2) with CTEPH and 25 healthy volunteers (39.3±10.1 years). All the patients underwent a six-minute walking test (6-MWT), transthoracic echocardiography, thorax organs radiography, right heart catheterization (RHC) and Laser Doppler flowmetry (LDF) with amplitude and frequency wavelet analysis of blood flow oscillations and evaluation of constrictory and dilatatoryskin resistive microvesselsfunctions. Results. In the PAH-CCD in relation to the CTEPH groupaccording to the RHC were noted significantly higher values of systolic pressure in pulmonary artery (93.2 and 77.8 mm Hg respectively) and venous mixted blood saturation(63 and 57% Hg respectively). On this background 6- MWT distance was 356 and 325 m, the Borg dyspnea scale index was on average 3.12 and 3.76 respectively. According to the LDF pulseoximetry PAH-CCD and CTEPH patients had 90.1 and 94.7% respectively. According to the LDF with amplitude and frequency wavelet analysis the PAH-CCD patients had sig-nificantly higher values of the amplitude of myogenic, respiratory and pulse sectionof blood flow modulation, and also increased constrictory activity smooth muscle cells of skin precapillary arterioles in response to the stretching at venous occlusion and decreased dilatatory reserve at post-occlusi-ve reactive hyperemia. According to the LDF the CTEPH patients had elongationof time development of microvessel constriction in response to acti-vation of sympathetic nervous systemin respiratory and cold tests. Conclusion. According to the LDF functional state of skin microvessels in systemic circulation of the CTEPH patients was comparable with control groupexcept for elongation of time development of microvessel reactions for sympathetic vasoconstrictor stimulations. The PAH-CCD patients demonstrated basal tonus decreasing of smooth muscle cells of skin precapillary arterioles in systemic circulation, which can be regarded as a manifestation of autoregulatory response to systemic hypoxia.

Особенности микроциркуляторного кровотока в коже у больных легочной гипертензией разной этиологии

Aim: to evaluate features of the functional state of microvascular bed of the skin in patients with pulmonary arterial hypertension associated to congenital cardiac disease (PAH-CCD) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods. In study included 25 patients (41.6±15.8) with PAH-CCD, 25 patients (48.8±14.2) with CTEPH and 25 healthy volunteers (39.3±10.1 years). All the patients underwent a six-minute walking test (6-MWT), transthoracic echocardiography, thorax organs radiography, right heart catheterization (RHC) and Laser Doppler flowmetry (LDF) with amplitude and frequency wavelet analysis of blood flow oscillations and evaluation of constrictory and dilatatoryskin resistive microvesselsfunctions. Results. In the PAH-CCD in relation to the CTEPH groupaccording to the RHC were noted significantly higher values of systolic pressure in pulmonary artery (93.2 and 77.8 mm Hg respectively) and venous mixted blood saturation(63 and 57% Hg respectively). On this background 6- MWT distance was 356 and 325 m, the Borg dyspnea scale index was on average 3.12 and 3.76 respectively. According to the LDF pulseoximetry PAH-CCD and CTEPH patients had 90.1 and 94.7% respectively. According to the LDF with amplitude and frequency wavelet analysis the PAH-CCD patients had sig-nificantly higher values of the amplitude of myogenic, respiratory and pulse sectionof blood flow modulation, and also increased constrictory activity smooth muscle cells of skin precapillary arterioles in response to the stretching at venous occlusion and decreased dilatatory reserve at post-occlusi-ve reactive hyperemia. According to the LDF the CTEPH patients had elongationof time development of microvessel constriction in response to acti-vation of sympathetic nervous systemin respiratory and cold tests. Conclusion. According to the LDF functional state of skin microvessels in systemic circulation of the CTEPH patients was comparable with control groupexcept for elongation of time development of microvessel reactions for sympathetic vasoconstrictor stimulations. The PAH-CCD patients demonstrated basal tonus decreasing of smooth muscle cells of skin precapillary arterioles in systemic circulation, which can be regarded as a manifestation of autoregulatory response to systemic hypoxia.

Clinical Utility of Central Venous Saturation for the Calculation of Cardiac Index in Cardiac Patients

BackgroundMixed venous saturation (MVS) obtained from the distal pulmonary artery (PA) during Swan-Ganz catheterization is the criterion standard for calculating cardiac output (CO) and cardiac index (CI) with the use of the Fick method. We think that calculating CI with the use of central venous saturation (CVS) instead of PA-MVS is both feasible and accurate. Earlier studies were small, enrolled heterogeneous patient populations, and resulted in inconsistent findings. MethodsAll patients undergoing right heart catheterization from January 2011 to January 2012 in our catheterization lab with simultaneous measurements of MVS obtained from the distal PA and CVS obtained from the superior vena cava (SVC) or right atrium (RA) were included. Out of the 902 patients enrolled, we excluded patients (n = 50) who had known cardiac shunt or dialysis fistula, had duplicate medical records, or were septic. We calculated the CI with the use of the assumed Fick method using both MVS (criterion standard) and CVS (SVC or RA saturations) in the remaining 852 patients. We measured the correlation and the agreement between the 2 methods with the use of the Pearson correlation coefficient and Bland-Altman analysis. ResultsTotals of 112 patients with simultaneous PA and RA saturation measurements (group I) and 740 patients with simultaneous PA and SVC saturation measurements (group II) were included. We found an excellent linear correlation between SVC and PA saturation (r = 0.928) and between RA and PA saturation (r = 0.95). There was also an excellent correlation between CI calculated with the use of PA saturation and CI calculated with the use of SVC (r = 0.87) or RA (r = 0.93) saturation. The mean bias of CVS-derived CI compared with MVS-derived CI (criterion standard) was −0.1 (95% limits of agreement [LOA] −1 to +0.77) in the SVC group and −0.006 (LOA −0.68 to +0.69) in the RA group. Patients with low CI had stronger correlation and smaller bias between the 2 methods compared with those with normal or high CI. The presence of baseline hypoxemia, valvular heart disease, or acute coronary syndrome had no significant effect on the correlation or the bias between the 2 methods. ConclusionsIn cardiac patients, CVS can be used as a surrogate to true MVS in the calculation of CI. This method is readily available in patients who have central venous access, and may aid in early goal-directed treatment when cardiogenic shock is suspected.

The prognostic significance of central hemodynamics in patients with cardiac amyloidosis

Background: The diagnosis of cardiac amyloidosis often requires a right heart catheterization with an endomyocardial biopsy. Although the central hemodynamics of the three main types of cardiac amyloidosis (AL, ATTRm, ATTRwt) have previously been described, the prognostic significance of these variables have not been fully explored.Objective: To compare the right heart catheterization variables between the three sub-groups of AL, ATTRm and ATTRwt, and describe if any of these variables are of prognostic significance.Methods: We conducted a retrospective cohort analysis of patients with biopsy confirmed cardiac amyloidosis between 1997 and 2011. Central hemodynamics as well as baseline clinical and laboratory characteristics were collected at the time of diagnosis. The prognostic significance of the central hemodynamics was evaluated. The internal review board of our institution approved the study.Results: Patients with ATTR and AL cardiac amyloidosis had similar central hemodynamic profiles of high filling pressures and low cardiac output with the exception of ATTR having higher pulmonary artery systolic pressure and pulmonary vascular resistance. Right atrial pressure (RAP), pulmonary artery diastolic pressure, pulmonary capillary wedge pressure and pulmonary artery saturation were individual predictors of death or heart transplantation (p < 0.05). However, when each was added to RAP they did not increase the predictive value compared to RAP alone.Conclusion: The central hemodynamics of ATTR and AL amyloidosis were found to be similar and RAP emerged as the main predictor of transplant-free survival.

Dissociation Between Severity of Takotsubo Cardiomyopathy and Presentation With Shock or Hypotension

Takotsubo cardiomyopathy (TTC) is increasingly well-recognized as a cause of chest-pain syndromes, especially in aging females. The most common complications of TTC occur in the first 24 hours post onset of symptoms and include shock and/or arrhythmias. We tested the hypothesis that the severity of early hypotension in TTC reflects the extent of myocardial involvement and dysfunction. In 80 consecutive TTC patients, correlates of blood pressure on the day of admission were sought via univariate followed by multivariate analysis. Mean systolic blood pressure (SBP) on day 1 was 120 ± 24 (SD) mm Hg. During the first 3 days of admission, 39% of patients had SBP <90 mm Hg, and 9% died and/or required intra-aortic balloon pump insertion. The extent of release of N-terminal pro-brain natriuretic peptide, with its potential correlate of associated vasodilator activity, varied inversely with pulmonary-artery saturation, a measure of cardiac output. However, there was no significant relationship between normetanephrine release and SBP. On multivariate analyses there was no significant relationship between SBP and (1) wall-motion score index (as an index of left-ventricular systolic dysfunction) or (2) T2 enhancement on cardiac magnetic resonance imaging and peak N-terminal pro-brain natriuretic peptide (as indices of myocardial inflammation). Although severe hypotension and shock occur commonly during acute stages of TTC, these complications are multifactorial in origin, probably representing a combination of impaired inotropic state and vasodilatation. Importantly, initial hypotension does not imply severe left ventricular inflammation or systolic dysfunction.