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Original Research: Pulmonary Vascular Disease |

Prognostic Relevance of Pulmonary Arterial Compliance in Patients With Chronic Heart FailurePulmonary Arterial Compliance in Heart Failure FREE TO VIEW

Paolo Pellegrini, MD; Andrea Rossi, MD; Michele Pasotti, MD; Claudia Raineri, MD; Mariantonietta Cicoira, MD; Stefano Bonapace, MD; Frank Lloyd Dini, MD; Pier Luigi Temporelli, MD; Corrado Vassanelli, MD; Rebecca Vanderpool, PhD; Robert Naeije, MD; Stefano Ghio, MD
Author and Funding Information

From the Department of Medicine (Drs Pellegrini, Rossi, Cicoira, Bonapace, and Vassanelli), Section of Cardiology, University of Verona, Verona, Italy; the Division of Cardiology (Drs Pasotti, Raineri, and Ghio), Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy; the Cardiac, Thoracic, and Vascular Department (Dr Dini), University of Pisa, Pisa, Italy; the Division of Cardiology (Dr Temporelli), Fondazione Salvatore Maugeri, IRCCS, Veruno, Italy; and the Department of Physiology (Drs Vanderpool and Naeije), Erasme Campus of the Free University of Brussels, Brussels, Belgium.

Correspondence to: Stefano Ghio, MD, Divisione di Cardiologia, Policlinico S. Matteo, Piazza Golgi 1, 27100 Pavia, Italy; e-mail: s.ghio@smatteo.pv.it


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(5):1064-1070. doi:10.1378/chest.13-1510
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Background:  Reduced pulmonary arterial compliance (Ca) is a marker of poor prognosis in idiopathic pulmonary arterial hypertension. We tested the hypothesis that pulmonary arterial Ca could be a predictor of outcome in patients with chronic heart failure (CHF).

Methods:  We enrolled 306 patients with CHF due to systolic left ventricular dysfunction (sLVD) who underwent a clinically driven right-sided heart catheterization. Pulmonary arterial Ca was measured by the ratio between stroke volume and pulse pressure (SV/PP). The primary end point was cardiovascular death; secondary end point was the composite of cardiovascular death, urgent heart transplantation, and appropriately detected and treated episode of ventricular fibrillation.

Results:  An inverse relationship was observed between SV/PP and pulmonary vascular resistance, the mean resistance-compliance product (RC-time) being 0.30 ± 0.2 s. In patients with pulmonary capillary wedge pressure (PCWP) < 15 mm Hg, the mean RC-time was 0.34 ± 0.14 s, and in patients with PCWP ≥ 15 mm Hg it was 0.28 ± 0.22 s. Eighty-seven patients died in a follow-up period of 50 ± 32 months. At receiver operating characteristic curve analysis, the optimal prognostic cutoff point of SV/PP was 2.15 mL/mm Hg. An elevated (> 2.15) SV/PP was more strongly associated with survival than any other hemodynamic variable; it was associated with poor prognosis both in patients with high (P = .003) and in patients with normal pulmonary vascular resistance (P = .005).

Conclusions:  Pulmonary arterial Ca is a strong prognostic indicator in patients with CHF with sLVD. Most importantly, its prognostic role is retained in patients with normal pulmonary vascular resistance.

Figures in this Article

In patients with chronic heart failure (CHF), the negative impact of pulmonary hypertension (PH) on prognosis seems modulated by right ventricular (RV) function.13 The most plausible explanation to these observations is that RV afterload and RV function are strictly related: PH is one of the main determinants of RV dysfunction, since the right ventricle, because of its specific anatomic characteristics, cannot easily tolerate pressure overload.4,5 The poor prognosis seems, therefore, related to the unfavorable coupling between the right ventricle and the pulmonary circulation, ultimately leading to RV failure.

From a pathophysiologic point of view, it has to be emphasized that the precise definition of RV afterload is not only difficult to derive but also complex to interpret. Afterload can be defined by an arterial elastance measured as a ratio of end-systolic pressure and stroke volume (SV) on a ventricular pressure-volume loop.6 This would be estimated by pulmonary vascular resistance (PVR) divided by heart rate, based on the assumption that mean pulmonary artery pressure is equal to RV end-systolic pressure. A more practical and equally valid definition of afterload is hydraulic load calculated from instantaneous pulmonary artery pressure and flow waves.7 A few decades ago, Reuben8 noted an inverse relationship between PVR and pulmonary arterial compliance (Ca) in the normal or diseased pulmonary circulation. This was revisited in a series of studies that showed that the product of PVR and pulmonary arterial Ca, or the time constant (resistance-compliance product [RC-time]) of the pulmonary circulation, remains constant over a wide range of severities, causes, and treatments of PH.911 This remarkable property of the pulmonary circulation has two consequences. The first is that pulmonary arterial Ca becomes a more important determinant of RV afterload than PVR when mean pulmonary artery pressure and PVR are only modestly elevated.12 The second is that RV oscillatory hydraulic load, or power, remains a constant fraction of total power, irrespective of mean pulmonary artery pressure.13 The only noticeable exception to the constancy of RC-time is PH secondary to left ventricular failure.14 In these patients, RC-time is decreased because of a stiffer pulmonary arterial tree caused by increased pulmonary venous pressure.15,16 A shortened RC-time implies an increased oscillatory component of hydraulic load.

Since in left ventricular failure PVR is usually only modestly elevated and the RC-time is shorter, one would expect pulmonary arterial Ca to be a major determinant of RV afterload. Therefore, we hypothesized that pulmonary arterial Ca would be a major determinant of survival in these patients. Accordingly, we analyzed the prognostic value of pulmonary arterial Ca in comparison with standard right-sided heart hemodynamic variables in a population of patients with CHF due to advanced systolic left ventricular dysfunction (sLVD). In addition, we sought to investigate whether pulmonary arterial Ca had a predictive role both in patients with normal and in patients with elevated PVR.

Study Patients

The study included 306 consecutive patients with CHF with sLVD, referred for heart failure management, heart transplantation evaluation, or both. The inclusion criteria were left ventricular ejection fraction ≤ 35% and etiology due to ischemic or hypertensive heart disease or idiopathic dilated cardiomyopathy. Exclusion criteria were organic valvular heart disease, previous surgery for valvular heart disease, other cardiomyopathies (such as restrictive or hypertrophic cardiomyopathy and arrhythmogenic RV cardiomyopathy), hospitalization due to heart failure in the previous 3 months, implant of a cardiac resynchronization device in the previous 6 months, diagnosis of severe COPD, and history of pulmonary embolism. All patients underwent right-sided heart catheterization as part of the diagnostic protocol for heart failure evaluation and transplantation eligibility assessment. Patients signed an informed consent agreement approved by the Institutional Review Board of Fondazione IRCCS Policlinico S.Matteo for observational, nonpharmacologic, nonsponsored studies, which complies with the Italian legislation on the privacy (Codex on the Privacy, D. Lgs. 30 giugno 2003, n. 196).

Hemodynamic Parameters

Right-sided heart catheterization was performed using a balloon-tipped catheter. The following hemodynamic parameters were measured or calculated: pulmonary capillary wedge pressure (PCWP); systolic, diastolic, and mean pulmonary artery pressure; pulmonary pulse pressure (PP); cardiac output (calculated by thermodilution or by Fick method); cardiac index; SV (obtained by dividing cardiac output by heart rate); right atrial pressure; and PVR, calculated as (mean pulmonary artery pressure − PCWP)/cardiac output. Pulmonary arterial Ca was estimated by dividing the blood volume driven from each heartbeat in the pulmonary vascular tree, namely the SV, by the corresponding change in the pulmonary artery pressure: pulmonary arterial compliance ≈ SV/PP [mL/mm Hg].

Follow-up

The primary end point was cardiovascular death. The secondary end point was the composite of cardiovascular death, urgent cardiac transplantation (United Network for Organ Sharing [UNOS] 1), and appropriately detected and treated episode of ventricular fibrillation. Cardiac transplantation and implantation of a biventricular device were considered censoring events. Survival data were obtained through follow-up visits of patients or, in the case of missed visits, by telephone contact.

Statistical Analysis

Continuous data are presented as mean ± SD. To study the clinical characteristics of patients with normal or reduced Ca, patients were grouped in tertiles of SV/PP, and differences among groups were assessed by t test, χ2, and analysis of variance, as appropriate. Survival and event-free survival were estimated by the Kaplan-Meier method and group differences assessed with the log-rank test. The optimal SV/PP cutoff value for predicting survival was identified from receiver operating characteristic (ROC) curve analysis. All hemodynamic parameters were dichotomized according to literature data. The independent association between SV/PP and prognosis was assess by means of Cox proportional hazard model. Bivariate Cox models were used to avoid multicollinearity among hemodynamic variables; however, results were similar when a full multivariate model was performed, including PCWP, mean pulmonary artery pressure, cardiac index, and PVR (data not shown). Statistical significance was set at a level of P < .05. A commercially available statistical software package was used (Statview 5.0; Abacus Concepts, Inc).

Table 1 shows the main demographic, clinical, hemodynamic, and echocardiographic characteristics of the entire population. The study included young patients, mainly affected by dilated cardiomyopathy, with advanced sLVD at echocardiography and reduced cardiac output at right-sided heart catheterization.

Table Graphic Jump Location
Table 1 —Clinical, Echocardiographic, and Hemodynamic Characteristics of the Study Population

Data are presented as mean ± SD or %. Total No. of patients = 306. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; bpm = beats/min; BSA = body surface area; IHD = ischemic heart disease; LVEDVI = left ventricular end-diastolic volume index; LVEF = left ventricular ejection fraction; mPAP = mean pulmonary artery pressure; NYHA = New York Heart Association; PCWP = pulmonary capillary wedge pressure; PP = pulse pressure; RAP = right atrial pressure; SV = stroke volume.

Relationship Between SV/PP and PVR

A wide range of SV/PP values were observed (from 0.63 to 11.8 mL/mm Hg) (Fig 1); the mean SV/PP was 3.1 ± 1.9 mL/mm Hg, meaning that 3.1 mL of blood are necessary to increase the PP of 1 mm Hg. An inverse relationship was observed between SV/PP and PVR in the entire population (Fig 2A); RC-time was 0.30 ± 0.2 s, and when fit to the data using the function SV/PP = RC-time/PVR, RC-time was 0.16 s. Figure 2B displays SV/PP as a function of PVR, with patients split into those with PCWP < 15 mm Hg and PCWP ≥ 15 mm Hg. The relationship between RC-time and PCWP in the entire population is shown in Figure 3. In the subgroup of patients with PCWP ≥ 15 mm Hg (mean PCWP of this subgroup = 24.9 mm Hg), the RC-time was 0.28 ± 0.22 s; using the relationship between RC-time and PCWP found by Tedford et al14 (RC-time = −0.0063[PCWP] + 0.46), the predicted RC-time was 0.30 s. In the subgroup of patients with PCWP < 15 mm Hg (mean PCWP of this subgroup = 9.7 mm Hg), the RC-time was 0.34 ± 0.14 s (predicted RC-time according to Tedford et al14 = 0.40 s).

Figure Jump LinkFigure 1. Distribution of SV/PP in the overall population. PP = pulse pressure; SV = stroke volume.Grahic Jump Location
Figure Jump LinkFigure 2. Effect of elevated PCWP on PVR-compliance relationship. A, Compliance as a function of PVR in all the subjects tested. B, Compliance as a function of PVR with patients split into those with PCWP < 15 mm Hg (■) and those with PCWP ≥ 15 mm Hg (△). PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance; RC-time = resistance-compliance product. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3. RC-time vs PCWP. See Figure 2 legend for expansion of abbreviations.Grahic Jump Location
Clinical and Hemodynamic Correlates of SV/PP

Patients were divided in three tertiles according to the SV/PP value. Table 2 shows the characteristics of the three groups of patients. For most variables there was a significant gradient in severity across tertiles, with patients in the first tertile (ie, those with lower pulmonary Ca) being the most symptomatic and those with the most advanced hemodynamic profile.

Table Graphic Jump Location
Table 2 —Patient Characteristics According to Tertiles of Pulmonary Artery Compliance

Data are presented as mean ± SD or %. PVR = pulmonary vascular resistance. See Table 1 legend for expansion of other abbreviations.

a 

P < .05 in comparison with group 3.

b 

P < .05 in comparison with group 2.

Survival According to SV/PP

During an average follow-up period of 50 ± 32 months, 87 patients died, four underwent emergency (UNOS 1) cardiac transplantation, and four had an appropriately detected and treated episode of ventricular fibrillation. At univariate analysis, pulmonary Ca was significantly associated with survival and with event-free survival (Table 3). At ROC curve analysis, the optimal cutoff point of SV/PP to predict survival was 2.15 mL/mm Hg, determined at a sensitivity of 0.71 and a specificity of 0.63; the area under the curve was 66.1%, with a 95% CI of 58.3% to 73.8%. At ROC curve analysis, the optimal cutoff point of SV/PP to predict event-free survival was 2.04 mL/mm Hg, determined at a sensitivity of 61% and a specificity of 74%; the area under the curve was 68.2%. Survival curves for patients with SV/PP ≥ 2.15 and < 2.15 are shown in Figure 4. Several bivariate analyses were performed to test the independent association between SV/PP and prognosis with other hemodynamic variables; it turned out that a reduced SV/PP was a stronger indicator of poor prognosis than high PCWP, high mean pulmonary artery pressure, low cardiac index, or high PVR (Table 4).

Table Graphic Jump Location
Table 3 —Association of SV/PP as a Continuous Variable and Survival, Using Different End Points

HR = hazard ratio. See Table 1 legend for expansion of other abbreviations.

Figure Jump LinkFigure 4. Survival according to SV/PP. Continuous line indicates patients with SV/PP equal to or above the optimal cutoff point to predict survival (2.15 mL/mm Hg); dotted line indicates patients with SV/PP below the optimal cutoff point. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Table Graphic Jump Location
Table 4 —Bivariate Cox Proportional Hazard Analysis Including SV/PP and One Hemodynamic Parameter at a Time

See Table 1, 2, and 3 legends for expansion of abbreviations.

Prognostic Role of SV/PP in Patients With Normal or Elevated PVR

Patients were grouped according to the presence of normal PVR (< 160 dyne/s/cm5) or elevated PVR (≥ 160 dyne/s/cm5); average PVR was 94 ± 38 dyne/s/cm5 in the first group and 297 ± 144 dyne/s/cm5 in the second group. In the subgroup of patients with normal PVR, SV/PP showed a wide and normal distribution (mean 3.7 ± 1.9; range 0.86-10.6; median 3.1). In this subgroup of patients, a reduced SV/PP was strongly associated with poor prognosis (hazard ratio [HR], 2.7; 95% CI, 1.3-5.6; P = .009) (Fig 5A). On the other hand, SV/PP showed a clearly nonnormal distribution (mean, 2.0 ± 1.4; range, 0.63-11.8; median, 1.5) in the subgroup of patients with elevated PVR. However, also in this subgroup of patients a reduced SV/PP was associated with poor prognosis (HR, 3.8; 95% CI, 1.5-9.7; P = .005) (Fig 5B).

Figure Jump LinkFigure 5. Survival according to SV/PP. A, Survival in the group of patients with normal PVR. B, Survival in the group of patients with elevated PVR. In both groups survival is significantly better in patients having pulmonary arterial compliance ≥ 2.15 mL/mm Hg. See Figure 1 and 2 legends for expansion of abbreviations.Grahic Jump Location

To our knowledge, this is the first study aiming at verifying the hemodynamic correlates and the prognostic implications of a reduced pulmonary arterial Ca in patients with sLVD with normal or elevated PVR. The main result of the present study is that a reduced pulmonary arterial Ca portends a poor prognosis independently of other well-known right-sided heart hemodynamic variables and that its negative prognostic impact is retained even in patients with normal PVR.

A reduced pulmonary arterial Ca is a powerful marker of poor prognosis in idiopathic pulmonary arterial hypertension.17 The reason is that in patients with pulmonary arterial hypertension, the outcome is predominantly determined by the response of the right ventricle to the increased afterload, and it has now become clear that in patients with PH the decrease in pulmonary arterial Ca plays an equally important role as resistance in determining RV afterload.1820 In patients with CHF, the relationship between vessel capacitance and outcome has been initially studied at the level of the systemic circulation. In patients with sLVD, a reduced thoracic aorta distensibility or an increased conduit vessel stiffness, as assessed by the simple systemic pulse pressure, were associated with reduced exercise tolerance and poor outcome.21,22 In recent years, the attention has shifted to the pulmonary circulation. In a huge clinical database including right-sided heart hemodynamic data of patients with precapillary and postcapillary PH, the presence of elevated PCWP was found to have a large impact on the relationship between pulmonary arterial Ca and resistance, significantly lowering Ca for any level of PVR, meaning that in PH due to heart failure the pulsatile, relative to the resistive load, is increased, therefore, enhancing the net RV afterload.14 The authors hypothesized that this mechanism might contribute to RV dysfunction in left-sided heart failure. In a more recent study aimed at assessing the hemodynamic and prognostic characteristics of passive and mixed PH in patients with sLVD, the presence of any PH was associated with lower pulmonary Ca; the authors showed that pulmonary Ca was useful to refine risk assessment in patients with PH sLVD.23

The present data add to previous observations, confirming that pulmonary arterial Ca has a strong relationship with survival in a general population of patients with CHF and specifically demonstrating its prognostic significance in patients with sLVD with normal PVR. In the present series, pulmonary arterial Ca significantly outperformed mean pulmonary artery pressure, PVR, PCWP, and cardiac index (separately considered) at bivariate analysis, emerging as the strongest hemodynamic predictor of subsequent cardiovascular death or hard events. To explain these results, one should consider that, similarly to what has been well established for patients with pulmonary arterial hypertension, the loading conditions of the right ventricle are a crucial determinant of the prognosis of patients with CHF.5 A better description of RV afterload is, therefore, of paramount importance in patients with CHF. The present study also aimed to analyze the role of pulmonary arterial Ca separately in patients with normal or elevated PVR. SV/PP showed a wide variability and a Gaussian distribution in patients with normal PVR, whereas it was very reduced in most patients with elevated PVR. However, most importantly, the SV/PP ratio retained a prognostic value in both subgroups. This finding is highly relevant from a clinical perspective, since it suggests that large vessel structural changes might precede the increase in PVR in patients with CHF. Unfortunately, although histopathologic studies of pulmonary artery tissue in patients with CHF with PH demonstrated important structural abnormalities, we have no histopathologic data in the absence of PH.24 In any case, the data are in agreement with the hypothesis formulated in patients with pulmonary arterial hypertension that the early phase of pulmonary vascular disease cannot be recognized at right-sided heart catheterization by an elevation of PVR but only by a reduction in pulmonay arterial Ca.17

Limitations

A major limitation of the study is the lack of other well-known markers of adverse prognosis in CHF, such as the exercise capacity at cardiopulmonary testing, mitral inflow pattern at Doppler echocardiography, or plasma levels of biomarkers. Nonetheless, the population investigated and the long follow-up make solid bases for further validation of our findings in selected populations of patients with CHF. A comprehensive measurement of RV afterload is given by the pulmonary arterial input impedance; this calculation requires synchronized high-fidelity pressure and flow measurements, a spectral analysis of the waveforms, and a mathematical elaboration to derive an impedance spectrum.7 Notwithstanding this, simplified descriptions of the pulmonary arterial circulation in terms of resistance and Ca have already been used in clinical settings. The role of reduced pulmonary Ca on recurrent hospitalizations was not addressed in the present study. Finally, the results do not apply to patients with heart failure with normal or slightly reduced systolic function.

In conclusion, pulmonary arterial Ca is a strong prognostic indicator in patients with CHF with sLVD; most importantly, its prognostic role is retained in patients having normal PVR, underscoring the necessity of a precise evaluation of the pulmonary circulation in all patients with CHF, regardless of the hemodynamic severity of the disease.

Author contributions: Dr Ghio is the guarantor of the content of the manuscript, including the data and analysis.

Dr Pellegrini: contributed to conception of the study, interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Rossi: contributed to conception of the study, interpretation and analysis of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Pasotti: contributed to acquisition and interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Raineri: contributed to acquisition and interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Cicoira: contributed to conception of the study, interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Bonapace: contributed to conception of the study, interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Dini: contributed to conception of the study, interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Temporelli: contributed to conception of the study, interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Vassanelli: contributed to interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Vanderpool: contributed to interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Naeije: contributed to interpretation of data, revision of the manuscript critically for important intellectual content, and final approval of the version to be published.

Dr Ghio: contributed to conception and design of the study, interpretation of data, drafting of the submitted article, and final approval of the version to be published.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Ca

compliance

CHF

chronic heart failure

HR

hazard ratio

PCWP

pulmonary capillary wedge pressure

PH

pulmonary hypertension

PP

pulse pressure

PVR

pulmonary vascular resistance

RC-time

resistance-compliance product

ROC

receiver operating characteristic

RV

right ventricular

sLVD

systolic left ventricular dysfunction

SV

stroke volume

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Figures

Figure Jump LinkFigure 1. Distribution of SV/PP in the overall population. PP = pulse pressure; SV = stroke volume.Grahic Jump Location
Figure Jump LinkFigure 2. Effect of elevated PCWP on PVR-compliance relationship. A, Compliance as a function of PVR in all the subjects tested. B, Compliance as a function of PVR with patients split into those with PCWP < 15 mm Hg (■) and those with PCWP ≥ 15 mm Hg (△). PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance; RC-time = resistance-compliance product. See Figure 1 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3. RC-time vs PCWP. See Figure 2 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4. Survival according to SV/PP. Continuous line indicates patients with SV/PP equal to or above the optimal cutoff point to predict survival (2.15 mL/mm Hg); dotted line indicates patients with SV/PP below the optimal cutoff point. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 5. Survival according to SV/PP. A, Survival in the group of patients with normal PVR. B, Survival in the group of patients with elevated PVR. In both groups survival is significantly better in patients having pulmonary arterial compliance ≥ 2.15 mL/mm Hg. See Figure 1 and 2 legends for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Clinical, Echocardiographic, and Hemodynamic Characteristics of the Study Population

Data are presented as mean ± SD or %. Total No. of patients = 306. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; bpm = beats/min; BSA = body surface area; IHD = ischemic heart disease; LVEDVI = left ventricular end-diastolic volume index; LVEF = left ventricular ejection fraction; mPAP = mean pulmonary artery pressure; NYHA = New York Heart Association; PCWP = pulmonary capillary wedge pressure; PP = pulse pressure; RAP = right atrial pressure; SV = stroke volume.

Table Graphic Jump Location
Table 2 —Patient Characteristics According to Tertiles of Pulmonary Artery Compliance

Data are presented as mean ± SD or %. PVR = pulmonary vascular resistance. See Table 1 legend for expansion of other abbreviations.

a 

P < .05 in comparison with group 3.

b 

P < .05 in comparison with group 2.

Table Graphic Jump Location
Table 3 —Association of SV/PP as a Continuous Variable and Survival, Using Different End Points

HR = hazard ratio. See Table 1 legend for expansion of other abbreviations.

Table Graphic Jump Location
Table 4 —Bivariate Cox Proportional Hazard Analysis Including SV/PP and One Hemodynamic Parameter at a Time

See Table 1, 2, and 3 legends for expansion of abbreviations.

References

Cappola TP, Felker GM, Kao WHL, Hare JM, Baughman KL, Kasper EK. Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk. Circulation. 2002;105(14):1663-1668. [CrossRef] [PubMed]
 
Ghio S, Gavazzi A, Campana C, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol. 2001;37(1):183-188. [CrossRef] [PubMed]
 
Ghio S, Temporelli PL, Klersy C, et al. Prognostic relevance of a non-invasive evaluation of right ventricular function and pulmonary artery pressure in patients with chronic heart failure. Eur J Heart Fail. 2013;15(4):408-414. [CrossRef] [PubMed]
 
Voelkel NF, Quaife RA, Leinwand LA, et al; National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006;114(17):1883-1891. [CrossRef] [PubMed]
 
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