Pulmonary Artery Catheterization Effectiveness Research Articles

The importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial

AimsPrevious studies have suggested venous congestion as a stronger mediator of negative cardio-renal interactions than low cardiac output, with neither factor having a dominant role. While the influence of these parameters on glomerular filtration have been described, the impact on diuretic responsiveness is unclear. The goal of this analysis was to understand the hemodynamic correlates of diuretic response in hospitalized patients with heart failure. Methods and resultsWe analyzed patients from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) dataset. Diuretic efficiency (DE) was defined as the average daily net fluid output per doubling of the peak loop diuretic dose. We evaluated a pulmonary artery catheter hemodynamic-guided cohort (n = 190) and a transthoracic echocardiogram (TTE) cohort (n = 324) where DE was evaluated with hemodynamic and TTE parameters. Metrics of “forward flow” such as cardiac index, mean arterial pressure and left ventricular ejection fraction were not associated with DE (p > 0.2 for all). Worse baseline venous congestion was paradoxically associated with better DE as assessed by right atrial pressure (RAP), right atrial area (RAA), and right ventricular systolic and diastolic area (p < 0.05 for all). Renal perfusion pressure (capturing both congestion and forward flow) was not associated with diuretic response (p = 0.84). ConclusionsWorse venous congestion was weakly associated with better loop diuretic response. Metrics of “forward flow” did not demonstrate any correlation with diuretic response. These observations raise questions about the concept of central hemodynamic perturbations as the primary drivers of diuretic resistance on a population level in HF.

Decoupling of Hemodynamics and Congestive Symptoms in Obese Patients With Heart Failure

Prior studies indicate significant physiological differences between obese and nonobese patients with heart failure (HF), but none have evaluated differences in hemodynamic patterns in these patient populations during treatment for acute decompensated HF (ADHF). In this study, we assessed differences in hemodynamic trends between obese and nonobese patients during treatment for ADHF. Obese (body mass index (BMI) >30, n = 63) and nonobese (BMI < 25, n = 69) patients with ADHF in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) study who had pulmonary artery catheterization data available through the duration of treatment were evaluated. Hemodynamics were analyzed at baseline and optimal day. Changes in BNP levels, weight, creatinine, BUN, 6MWT, orthopnea and dyspnea scores were assessed. Despite similar baseline hemodynamics, obese patients had significantly less absolute and relative pulmonary arterial wedge pressure (PAWP) reduction (-16 ± 28 vs -32 ± 29%; P = 0.03) during treatment. Obese patients also had higher PAWPs (19.9 + 8 vs 15.5 + 6.8 mmHg; P = 0.01) and PA pressures at optimization compared with nonobese patients. Obese and nonobese patients had similar relative improvements in weight, BNP, 6-minute walk test distance, dyspnea and orthopnea scores, and similar changes in creatinine and BUN levels. Obese patients treated for ADHF display less reduction in invasively measured left heart filling pressures, despite similar improvements in symptoms, weight loss, and noninvasive surrogates of congestion. Our findings suggest a degree of decoupling between left heart filling pressures and congestive symptoms in obese patients undergoing treatment for ADHF.

Coronary perfusion pressure is associated with adverse outcomes in advanced heart failure.

Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) would be associated with adverse outcomes in heart failure. Myocardial perfusion impacts the contractile efficiency thus a low CPP would signal low myocardial perfusion in the face of increased cardiac demand as a result of volume overload. We analyzed patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial using Cox Proportional Hazards regression for the primary outcome of the composite risk of death, heart transplantation, or left ventricular assist device [(LVAD). DT × LVAD] and the secondary outcome of the composite risk of DT × LVAD and heart failure hospitalization (DT × LVADHF). CPP was calculated as the difference between diastolic blood pressure and pulmonary artery wedge pressure. Heart failure categories (ischemic vs non-ischemic) were also stratified based on CPP strata. The 158 patients (56.7 ± 13.6years, 28.5% female) studied had a median CPP of 40mmHg (IQR 35-52mmHg). During 6months of follow-up, 35 (22.2%) had the composite primary outcome and 109 (69.0%) had the composite secondary outcome. When these outcomes were then stratified based on the median, CPP was associated with these outcomes. Increasing CPP was associated with lower risk of both the primary outcome of DT × LVAD (HR 0.96, 95% CI 0.94-0.99 p = .002) and as well as the secondary outcome of DT × LVADHF (p = .0008) There was significant interaction between CPP and ischemic etiology (p = .04). A low coronary artery perfusion pressure below (median) 40mmHg in patients with advanced heart failure undergoing invasive hemodynamic monitoring with a pulmonary artery catheter was associated with adverse outcomes. CPP could useful in guiding risk stratification of advanced heart failure patients and timely evaluation of advanced heart failure therapies.

Decongestion Models and Metrics in Acute Heart Failure: ESCAPE Data in the Age of the Implantable Cardiac Pressure Monitor.

The United States Food and Drug Administration restricts the use of implantable cardiac pressure monitors to patients with New York Heart Association (NYHA) class III heart failure (HF). We investigated whether single-pressure monitoring could predict survival in HF patients as part of a model constructed using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial. We validated survival models in 204 patients, using all-cause 180-day mortality. Two levels of model complexity were tested: 1) a simplified 1-pressure model based on pulmonary artery mean pressure ([PAM]1P) (information obtainable from an implanted intracardiac monitor alone), and 2) a pair of 5-variable risk score models based on right atrial pressure (RAP) + pulmonary capillary wedge pressure (PCWP) ([RAP+PCWP]5V) and on RAP + PAM ([RAP+PAM]5V). The more complex models used 5 dichotomous variables: a congestion index above a certain threshold value, baseline systolic blood pressure of <100 mmHg, baseline blood urea nitrogen level of ≥ 34 mg/dL, need for cardiopulmonary resuscitation or mechanical ventilation, and posttreatment NYHA class IV status. The congestion index was defined as posttreatment RAP+PCWP or posttreatment RAP+PAM, with congestion thresholds of 34 and 42 mmHg, respectively (median pulmonary catheter indwelling time, 1.9 d). The 5-variable models predicted survival with areas under the curve of 0.868 for the (RAP+PCWP)5V model and 0.827 for the (RAP+PAM)5V model, whereas the 1-pressure model predicted survival with an area under the curve of 0.718. We conclude that decongestion as determined by hemodynamic assessment predicts survival in HF patients and that it may be the final pathway for treatment benefit despite improvements in pharmacologic intervention since the ESCAPE trial.

Systemic arterial pulsatility index (SAPi) predicts adverse outcomes in advanced heart failure patients.

Ventriculo-arterial (VA) coupling has been shown to have physiologic importance in heart failure (HF). We hypothesized that the systemic arterial pulsatility index (SAPi), a measure that integrates pulse pressure and a proxy for left ventricular end-diastolic pressure, would be associated with adverse outcomes in advanced HF. We evaluated the SAPi ([systemic systolic blood pressure-systemic diastolic blood pressure]/pulmonary artery wedge pressure) obtained from the final hemodynamic measurement in patients randomized to therapy guided by a pulmonary arterial catheter (PAC) and with complete data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Cox proportional hazards regression was performed for the outcomes of (a) death, transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and (b) DTxLVAD. Among 142 patients (mean age 56.8±13.3years, 30.3% female), the median SAPi was 2.57 (IQR 1.63-3.45). Increasing SAPi was associated with significant reductions in DTxLVAD (HR 0.60 per unit increase in SAPi, 95% CI 0.44-0.84) and DTxLVADHF (HR 0.81 per unit increase, 95% CI 0.70-0.95). Patients with a SAPi ≤ 2.57 had a marked increase in both outcomes, including more than twice the risk of DTxLVAD (HR 2.19, 95% CI 1.11-4.30) over 6months. Among advanced heart failure patients with invasive hemodynamic monitoring in the ESCAPE trial, SAPi was strongly associated with adverse clinical outcomes. These findings support further investigation of the SAPi to guide treatment and prognosis in HF undergoing invasive hemodynamic monitoring.

Inferior Vena Cava Diameter Measurement Provides Distinct and Complementary Information to Right Atrial Pressure in Acute Decompensated Heart Failure

Inferior vena cava (IVC) measurements correlate only modestly with right atrial pressure (RAP). Part of this inaccuracy is due to the high compliance of the venous system, where a large change in blood volume may result in only a small change in pressure. As such, the information provided by the IVC may be different rather than redundant. We analyzed patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial who had both pulmonary artery catheter and IVC measurements at baseline (n = 108). There was only a modest correlation between baseline RAP and IVC diameter (r = 0.41; P < 0.001). Hemoconcentration, defined as an increase in hemoglobin levels between admission and discharge, was correlated with decrease in IVC diameter (r = 0.35; P = 0.02) but not with a decrease in RAP (r = 0.01; P = 0.95). When patients had both IVC and RAP measurements that were below the median, survival rates were superior to the rates of those who had only 1 measurement below the median, and when both rates were above the median, patients fared the worst (P = 0.002). IVC and RAP have limited correlation with each another, and changes in intravascular volume appear to correlate better with IVC diameter rather than with RAP. Furthermore, complementary information is provided by pressure and volume assessments in acute decompensated heart failure.

Pulmonary artery catheterization in acute myocardial infarction complicated by cardiogenic shock: A review of contemporary literature.

Acute myocardial infarction (AMI) with left ventricular (LV) dysfunction patients, the most common cause of cardiogenic shock (CS), have acutely deteriorating hemodynamic status. The frequent use of vasopressor and inotropic pharmacologic interventions along with mechanical circulatory support (MCS) in these patients necessitates invasive hemodynamic monitoring. After the pivotal Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial failed to show a significant improvement in clinical outcomes in shock patients managed with a pulmonary artery catheter (PAC), the use of PAC has become less popular in clinical practice. In this review, we summarize currently available literature to summarize the indications, clinical relevance, and recommendations for use of PAC in the setting of AMI-CS.

Combined Hemodynamic Measures of Left and Right Ventricular Function Predict Clinical Outcomes the ESCAPE Trial

<h3>Purpose</h3> We evaluated the utility of combined assessment of left and right ventricular function for prediction of clinical outcomes in hospitalized heart failure patients. <h3>Methods</h3> The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. Aortic pulsatility index (API), (systolic - diastolic blood pressure)/pulmonary capillary wedge pressure, and pulmonary artery pulsatility index (PAPI), (systolic pulmonary arterial pressure - diastolic pulmonary arterial pressure)/right atrial pressure, were computed from the final hemodynamic measurements. Participants were grouped as: Low API/Low PAPI, Low API/High PAPI, High API/Low PAPI, and High API/High PAPI based on cut-points of 2.9 and 2.6 for API and PAPI, respectively, which were previously determined by our group using receiver operator characteristic analysis. The primary outcome was need for left ventricular assist device or heart transplant, or death at six-months post-hospital discharge. Secondary outcomes included any rehospitalization and cardiac rehospitalization. <h3>Results</h3> Of 433 participants enrolled in the ESCAPE trial, 142 had complete final hemodynamic data with which to calculate API and PAPI. Low API/Low PAPI was associated with the primary outcome when compared to the 3 other groups, HR 3.58 (95%CI 1.95-6.57), p<0.0001). Kaplan-Meier analysis indicated more participants with Low API/Low PAPI achieved the primary outcome (56.4% vs 19.4%, p<0.0001). Low API/Low PAPI was associated with higher risk of any rehospitalization (HR 1.64, 95%CI 1.05-2.57, p=0.031) or cardiac rehospitalization (HR 2.43, 95%CI 1.08-2.99, p=0.023) when compared to the 3 other groups. <h3>Conclusion</h3> Combined measurements of left and right ventricular function using API and PAPI is associated with significant clinical outcomes in patients hospitalized with acute decompensated heart failure, and may be useful for prognostic risk stratification.

Aortic pulsatility index predicts clinical outcomes in heart failure: a sub-analysis of the ESCAPE trial.

AimsAortic pulsatility index (API), calculated as (systolic–diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel haemodynamic measurement representing both cardiac filling pressures and contractility. We hypothesized that API would better predict clinical outcomes than traditional haemodynamic metrics of cardiac function.Methods and resultsThe Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual‐level data were used. Routine haemodynamic measurements, including Fick cardiac index (CI), and the advanced haemodynamic metrics of API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated after final haemodynamic‐monitored optimization. The primary outcome was a composite endpoint of death or need for orthotopic heart transplant (OHT) or left ventricular assist device (LVAD) at 6 months. A total of 433 participants were enrolled in the ESCAPE trial of which 145 had final haemodynamic data. Final API measurements predicted the primary outcome, OR 0.47 (95% CI 0.32–0.70, P < 0.001), while CI, CPO, and PAPI did not. Receiver operator characteristic analyses of final advanced haemodynamic measurements indicated API best predicted the primary outcome with a cutoff of 2.9 (sensitivity 76.2%, specificity 55.3%, correctly classified 61.4%, area‐under‐the‐curve 0.71), compared with CPO, CI, and PAPI. Kaplan–Meier analyses indicated API ≥ 2.9 was associated with greater freedom from the primary outcome (83.5%), compared with API < 2.9 (58.4%), P = 0.001. While PAPI was also significantly associated, CI and CPO were not.ConclusionsThe novel haemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared with traditional invasive haemodynamic metrics of cardiac function.

Abstract 14388: Aortic Pulsatility Index Strongly Predicts Clinical Outcomes in Heart Failure Patients: A Sub-analysis of the Escape Trial

Introduction: Aortic pulsatility index (API), calculated as (systolic - diastolic blood pressure)/pulmonary capillary wedge pressure, is a novel hemodynamic measurement representing cardiac filling pressures and contractility. Hypothesis: API would better predict clinical outcomes than traditional hemodynamic metrics of cardiac function in decompensated heart failure patients. Methods: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. API, cardiac power output (CPO), Fick cardiac index (CI), and pulmonary artery pulsatility index (PAPI) were calculated after final hemodynamic-monitored optimization. The primary outcome, assessed by univariable analysis, was combined death or need for heart transplant or left ventricular assist device at six months. Receiver operator characteristic (ROC) analyses were used to determine the cutoff value, from which Kaplan-Meier (KM) curves were constructed. Results: A total of 433 patients were enrolled in the ESCAPE trial, of which 155 had accurate final hemodynamic data. Of these, 45 (29%) experienced the primary outcome. Final API measurements predicted the primary outcome, OR 0.45 (95% CI 0.30-0.70, p&lt;0.001), while CI, CPO, and PAPI did not. ROC analyses of final advanced hemodynamic measurements indicated API best predicted the primary outcome with a cutoff (sensitivity, specificity, correctly classified, AUC) of 2.9 (76.2%, 55.3%, 61.4%, 0.71), compared to CPO 0.69 (57.8%, 57.8%, 57.4%, 0.57), CI 2.2 (50.0%, 48.2%, 48.7%, 0.52), and PAPI 2.6 (60.5%, 64.5%, 63.3%, 0.64). KM analyses indicated API (83.5% vs 58.4%, p=0.001) and PAPI (78.3% vs 59.0%, p=0.03) were predictive of freedom from the primary outcome, but not CPO or CI. Conclusions: The novel hemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared to traditional invasive hemodynamic metrics of cardiac function.

Abstract 15111: Aortic Pulsatility Index Predicts Heart Failure Rehospitalization: A Sub-analysis of the Escape Trial

Introduction: Aortic pulsatility index (API), calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel hemodynamic measurement representing cardiac filling pressures and contractility. Hypothesis: API would predict heart failure hospitalizations in acutely decompensated heart failure participants in the Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness (ESCAPE) trial. Methods: From the ESCAPE trial individual-level data API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated, as well as reported routine invasive hemodynamics at baseline and after final hemodynamic-monitored optimization. Outcomes assessed were need for any rehospitalization and time to any first rehospitalization. Univariable analysis was conducted to assess rehospitalization. Negative binomial regression was used to analyze duration of time from discharge to first rehospitalization. Results: A total of 433 patients were enrolled in the ESCAPE trial. 189 patients had complete, accurate baseline hemodynamic data and were included in this analysis. No baseline hemodynamic measurements were associated with either outcome, except pulmonary artery (PA) diastolic pressure which predicted rehospitalization (OR 1.05 (95% CI 1.00-1.05, p= 0.02). Final API, OR 0.75 (95% CI 0.60-1.00, p= 0.03) and PAPI, OR 0.90 (95% CI 0.80-1.00, p= 0.03) predicted the need for any rehospitalization. Final API, OR 0.84 (95% CI 0.73-0.97, p= 0.02), and PA diastolic pressure, OR 1.03 (95% CI 1.01-1.06, p= 0.02), were associated with duration of time from discharge to any first hospitalization. Conclusions: The novel hemodynamic measurement API better predicted rehospitalization and time to rehospitalization in the ESCAPE trial when compared to routine, and other advanced invasive hemodynamic measurements.

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.

Higher Diuretic Requirements in Acute Heart Failure With Admission Hyponatraemia Versus Normonatraemia

BackgroundDiuretic requirements in patients with acute decompensated heart failure (ADHF) and hyponatraemia versus normonatraemia on admission has not been previously explored. MethodsThe Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial dataset was utilised to examine the characteristics and diuretic requirements of patients with ADHF with hyponatraemia or normonatraemia on admission. ResultsPatients with ADHF and admission hyponatraemia (n = 103, average Na 130.2 meq/L) had a higher degree of congestion evident in higher frequency of jugular venous distension (JVD) >12 cmH2O (p = 0.007), 2+ lower extremity oedema (p = 0.001), and higher right atrial pressure (p = 0.007), compared with normonatraemic patients (n = 327, average Na 138.6 meq/L). Despite a similar baseline furosemide dose in both groups (median 200 mg), the hyponatraemia group received higher in-hospital furosemide (280 vs. 200 mg, in both groups, respectively, p < 0.001) which represented a higher percentage of furosemide utilisation relative to baseline, compared with the normonatraemia group (33% vs 0%, in both groups respectively, p = 0.007). With in-hospital diuresis, the Na level of hyponatraemic subjects started significantly increasing at discharge and up to 6 months after randomisation—all relative to baseline. Hyponatraemic patients had significantly lower systolic blood pressure (SBP) longitudinally at multiple time points compared with normonataremic patients, but it did not further decrease despite the higher furosemide dose in the former group. ConclusionPatients with ADHF and hyponatraemia on admission had a higher degree of congestion and required higher doses of furosemide, compared with normonatraemic subjects. The lower Na and SBP in this instance should not lead to withholding or minimising diuretic dosage which should rather be dictated by volume status.

Abstract 16789: Pulmonary-Systemic Effective Arterial Elastance Ratio is Associated With Increased Adverse Outcomes in Advanced Heart Failure

Introduction: Advanced heart failure (HF) is characterized by ventricular arterial (VA) uncoupling and inefficient myocardial contractile mechanics. Effective arterial elastance (Ea) is a marker of total arterial load on the ventricle. There is paucity of data on the interaction between pulmonary-systemic effective arterial elastance (PSEa) [(Pulmonary systolic pressure/Stroke volume)/ (systolic blood pressure x 0.9)/Stroke volume)] with clinical outcomes in HF. Hypothesis: We hypothesized that increasing PSEa would be associated with higher adverse outcomes in patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Methods: Cox proportional hazards analysis and Kaplan Meier survival curves were used to assess associations between PSEa at end of pulmonary artery catheter (PAC) monitored therapy with clinical outcomes of time to death, transplant or LVAD (DTxLVAD) and time to death, transplant, LVAD or heart failure re-hospitalization (DTxLVADHF) over 6 months. Results: Among 165 patients (age 56.6 +/- 13.7 years, 29.1% female), the median PSEa ratio at the last PAC measurement was 0.48 (IQR 0.38 to 0.62). During 6 months of follow-up, PSEa ratio was significantly associated with the outcome of DTxLVAD in a Cox proportional hazards model (HR 2.18 per 0.25 increase in PSEa; 95% CI 1.41-3.37; P=0.0004), as well as the outcome of DTxLVADHF (HR 1.39 per 0.25 increase in PSEa; 95% CI 1.04-1.86; P=0.026); Kaplan-Meier curves demonstrated an increased rate of DTxLVAD in PSEa among patient in the highest quartile of PSEa (≥0.62) during follow- up period (Figure). Conclusion: PSEa is a novel marker of interventricular arterial coupling, that is associated with increased adverse events in advanced HF. These findings support further investigation of PSEa to guide risk stratification and prognosis in HF.

Abstract 17033: Comparative Effectiveness of Pulmonary Vascular Resistance, Capacitance, and Resistance-Capacitance Time in the ESCAPE Trial

Introduction: Right ventricular (RV) function portends adverse outcomes in heart failure (HF). Markers of RV load include pulmonary vascular resistance (PVR), pulmonary capacitance (PC), and the Resistance-Capacitance Time (RCT), a product of PVR and PC. The impact of changes in these indices during hemodynamic optimization is unknown. Hypothesis: PVR, PC and RCT after therapy and changes in these indices during therapy would be differentially associated with outcomes in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization (PAC) Effectiveness (ESCAPE) trial. Methods: Using Cox proportional hazards regression and Kaplan Meier survival analysis, we analyzed associations of PVR, PC, and RCT indices with the outcomes of death, transplantation, and left ventricular assist device (DTxLVAD) and a combined rehospitalization outcome (DTxLVADH) during 6 months follow-up. Results: Among 138 patients (age 56.9 ± 13.6 years, 30.4% female), PVR at the end of therapy was associated with increased DTxLVAD (HR 1.28 per 1 W.U. increase; 95% CI 1.11-1.47; P=0.0007), and final PC was associated with a decreased DTxLVAD (HR 0.60 per unit PC increase; 95% CI 0.41-0.87; P=0.0007). The final RCT was not associated with DTxLVAD (HR 0.70; CI 0.48-1.03; P=0.07). Changes in PVR during therapy (median -0.38 W.U.; IQR -1.57 to 0.62 W.U.) were associated with increased rehospitalization (DTxLVADH) during follow-up (HR 1.13; 95% CI 1.02-1.25; P=0.02). In a binary analysis, patients with an increase in PVR &gt; 0.1 W.U. during therapy had a trend for more DTxLVADH events (log-rank P=0.058; Figure). Changes in PVR and PC during therapy were not associated with survival. Conclusions: Final PVR and PAC measurements but not changes in these parameters during therapy were associated with survival, although changes in PVR during therapy were associated with rehospitalization. More studies are needed to understand the utility of RV load parameters in HF therapy.

Worsening renal function during decongestion among patients hospitalized for heart failure: Findings from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial

Worsening renal function (WRF) can occur throughout a hospitalization for acute heart failure (HF). However, decongestion can be measured in different ways and the prognostic implications of WRF in the setting of different measures of decongestion are unclear. Patients (N = 433) from the ESCAPE were classified by measures of decongestion during hospitalization: hemodynamic (right atrial pressure ≤8 mmHg and/or wedge pressure ≤15 mmHg at discharge), clinical (≤1 sign of congestion at discharge), hemoconcentration (any increase in hemoglobin) and estimated plasma volume using the Hakim formula (5% reduction in plasma volume). WRF was defined as creatinine increase ≥0.3 mg/dl during hospitalization. The association between WRF and 180-day all-cause death was assessed. Successful decongestion was observed in 124 (60%) patients by hemodynamics, 204 (49%) by clinical exam, 173 (47%) by hemoconcentration, and 165 (45%) by plasma volume. There was no agreement between the hemodynamic assessment and other decongestion measures in up to 43% of cases. Persistent congestion with concomitant WRF at discharge was associated with worse outcomes compared to patients without congestion and WRF. Among patients decongested at discharge, in-hospital WRF was not significantly associated with 180-day all-cause death, when using hemodynamic, clinical or estimated plasma volume as measures of decongestion (P > .05 for all markers). In patients hospitalized for HF, although there was disagreement across common measures of decongestion, in-hospital WRF was not associated with increased hazard of all-cause mortality among patients successfully decongested at discharge.

Prognostic Impact of Pulmonary Artery Pulsatility Index (PAPi) in Patients With Advanced Heart Failure: Insights From the ESCAPE Trial

BackgroundThe pulmonary artery pulsatility index (PAPi), defined as the ratio of pulmonary artery pulse pressure to right atrial pressure, emerged as a powerful predictor of right ventricular (RV) failure in patients with acute inferior myocardial infarction and those undergoing left ventricular assist device placement; however, its prognostic utility in the advanced heart failure population remains largely unknown. Methods and ResultsWe comparatively analyzed PAPi with traditional indices of RV function including RV stroke work index and right atrial/pulmonary capillary wedge pressure ratio (RAP/PCWP) in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. Median PAPi score was 2.35 in 190 patients. PAPi was significantly associated with clinical (jugular venous distention, ascites, edema), echocardiographic (right atrial size, vena cava size, tricuspid regurgitation velocity), and hemodynamic signs of RV failure (RAP, PCWP); all P < .05. In addition, PAPi was associated with the measures of left ventricular function, including ejection fraction, cardiac index, and PCWP (all P < .05). In Cox regression analysis, PAPi was an independent predictor of primary endpoint of death or hospitalization at 6 months (hazard ratio 0.91 [95% confidence interval 0.84–0.99], P = .022), whereas RA pressure, RV stroke work index, or RA/PCWP were not. ConclusionsPAPi serves as a marker of RV dysfunction and strongly predicts adverse clinical events in patients with advanced heart failure. Incorporating PAPi into existing risk models can substantially improve patient selection for advanced therapies and clinical outcomes in this population.

Post-discharge rise in BNP and rehospitalization for heart failure.

The B‑type natriuretic peptide (BNP) level on discharge of patients hospitalized with decompensated heart failure (HF) is widely considered as the "baseline" value, and treatment should be targeted to maintain this level. The prognostic value of an increase in BNP level from discharge to the 1‑month follow-up in predicting rehospitalization has not been previously explored. The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial data were utilized to determine whether an increase in BNP level from discharge to the 1‑month follow-up is associated with ahigher risk of rehospitalization. The study endpoints were all-cause rehospitalization up to 6months following randomization. Among 44patients (mean age, 56years, 71% men) who had their BNP levels checked on discharge and at the 1‑month follow-up, the average BNP level on discharge of the whole cohort was 467 pg/ml, which increased to 919 pg/ml at 1month (p = 0.001). The median and interquartile range of the magnitude of rise in BNP level from discharge to 1‑month follow-up was higher in rehospitalized compared with non-rehospitalized patients (329 [11, 956] vs. 44 [-90, 316]pg/ml, p = 0.039, in both groups, respectively). Receiver operator characteristic curves showed that the magnitude of the rise in BNP from discharge to the 1‑month follow-up had an area under the curve of 0.686 (p = 0.0255) in predicting all-cause rehospitalization. Rehospitalized and non-rehospitalized patients had similar degree of clinical congestion and comparable BNP level on hospital discharge. The magnitude of the rise in BNP level from discharge to the 1‑month follow-up is auseful prognostic factor that predicts rehospitalization in patients with HF.

Plasma Volume and Renal Function Predict Six-Month Survival after Hospitalization for Acute Decompensated Heart Failure

Background: Plasma volume (PV) is contracted in stable patients with heart failure (HF) due to decongestion strategies. On the other hand, increased PV can adversely affect the trajectory of HF. We therefore examined the effects of increased percentage change in PV (%ΔPV), blood urea nitrogen (BUN), and %ΔPV stratified by BUN and glomerular filtration rate (GFR) on survival after discharge in patients hospitalized for acute decompensated HF (ADHF). Methods: We used the Strauss-Davis-Rosenbaum formula to calculate the %ΔPV between baseline and hospital discharge in a cohort from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial (ESCAPE). Kaplan-Meier curves were constructed for survival over 6 months. Cox proportional hazards regression was used to obtain adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between survival after discharge and %ΔPV, BUN, and %ΔPV stratified by BUN and GFR. Results: Of the 324 patients included in our study (age 56.1 ± 13.6 years, 26.5% female), those with increased or no %ΔPV at discharge were less likely to survive at 6 months compared with those having reduced %ΔPV (log rank, p = 0.0093). Increased %ΔPV (HR 1.08 per 10% increase; 95% CI: 1.02-1.14) and increased BUN at discharge (HR 1.02 per mg/dL; 95% CI: 1.01-1.03) were independently associated with worse survival. Decreasing %ΔPV had a greater association with improved survival in patients with discharge BUN <31 mg/dL (p = 0.02) and discharge GFR >40 mL/min/1.73 m² (p = 0.047). Conclusions: Increased %ΔPV and BUN at discharge predicted worse 6-month survival in patients with ADHF. Decreased %ΔPV with low BUN or high GFR at discharge was associated with improved survival.

Clinical Impact of Changes in Hemodynamic Indices of Contractile Function During Treatment of Acute Decompensated Heart Failure

BackgroundThe objective of this work was to determine the impact of improving right ventricular versus left ventricular stroke work indexes (RVSWI vs LVSWI) during therapy for acute decompensated heart failure (ADHF). Methods and ResultsCox proportional hazards regression and logistic regression were used to analyze key factors associated with outcomes in 175 patients (mean age 56.7 ± 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplantation, or ventricular assist device implantatation (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (ΔRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (hazard ratio [HR] 0.923, 95% confidence interval [CI] 0.871–0.979) per 0.1 mm Hg⋅L⋅m−2 increase); however, increasing LVSWI (ΔLVSWI) had only a nonsignificant association with decreased DVADTXHF (P = .11) In a multivariable model, patients with ΔRVSWI ≤1.07 mm Hg⋅L⋅m−2 and ΔLVSWI ≤4.57 mm Hg⋅L⋅m−2 had a >2-fold risk of DVADTXHF (HR 2.05, 95% CI 1.23–3.41; P = .006). ConclusionCompared with left ventricular stroke work, increasing right ventricular stroke work during treatment of ADHF was associated with better outcomes. The results promise to inform optimal hemodynamic targets for ADHF.