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Original Research: Pulmonary Vascular Disease |

Echocardiography of Right Ventriculoarterial Coupling Combined With Cardiopulmonary Exercise Testing to Predict Outcome in Heart FailureRight-Sided Heart and Cardiopulmonary Test FREE TO VIEW

Marco Guazzi, MD, PhD; Robert Naeije, MD; Ross Arena, PhD; Ugo Corrà, MD; Stefano Ghio, MD; Paul Forfia, MD; Andrea Rossi, MD; Lawrence P. Cahalin, MD; Francesco Bandera, MD; Pierluigi Temporelli, MD
Author and Funding Information

From the Heart Failure Unit (Drs Guazzi and Bandera), University of Milano, IRCCS Policlinico San Donato, Milan, Italy; the Department of Pathophysiology (Dr Naeije), Faculty of Medicine, Free University of Brussels, Brussels, Belgium; the Department of Physical Therapy (Dr Arena), College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL; Fondazione “Salvatore Maugeri” (Drs Corrà and Temporelli), IRCCS, Veruno, Italy; the Department of Cardiology (Dr Ghio), Fondazione IRCCS Policlinico San Matteo, University Hospital, Pavia, Italy; Cardiovascular Medicine Division (Dr Forfia), Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; the Department of Biomedical and Surgical Sciences (Dr Rossi), Cardiology Section, University of Verona, Verona, Italy; and the Department of Physical Therapy (Dr Cahalin), Leonard M. Miller School of Medicine, University of Miami, Miami, FL.

CORRESPONDENCE TO: Marco Guazzi, MD, PhD, Heart Failure Unit - IRCCS Policlinico San Donato, University of Milano, Department of Biomedical Sciences for Health, Piazza Malan, 1 20097, San Donato Milanese, Milan, Italy; e-mail: marco.guazzi@unimi.it


FUNDING/SUPPORT: This study was supported by the Monzino Foundation, Milan, Italy.

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


Chest. 2015;148(1):226-234. doi:10.1378/chest.14-2065
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BACKGROUND:  Pulmonary hypertension, which is related to right ventricular (RV) failure, indicates a poor prognosis in heart failure (HF). Increased ventilatory response and exercise oscillatory ventilation (EOV) also have a negative impact. We hypothesized that the severity classification of HF and risk prediction could be improved by combining functional capacity with cardiopulmonary exercise testing (CPET) and RV-pulmonary circulation coupling, as evaluated by the tricuspid annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure (PASP) relationship.

METHODS:  Four hundred fifty-nine patients with HF were assessed with Doppler echocardiography and CPET and were tracked for outcome. The subjects were followed for major cardiac events (cardiac mortality, left ventricular assist device implant, or heart transplant). Cox regression and Kaplan-Meier analyses were performed with TAPSE and PASP as individual measures that were then combined into a ratio form.

RESULTS:  The TAPSE/PASP ratio (TAPSE/PASP) was the strongest predictor, whereas the New York Heart Association classification and EOV added predictive value. A four-quadrant group prediction risk was created based on TAPSE (< 16 mm or ≥ 16 mm) vs PASP (< 40 mm Hg or ≥ 40 mm Hg) thresholds and the CPET variables distribution as follows: group A (TAPSE > 16 mm and PASP < 40 mm Hg) presented the lowest risk (hazard ratio, 0.17) and best ventilation; group B exhibited a low risk (hazard ratio, 0.88) with depressed TAPSE (< 16 mm) and normal PASP, a preserved peak oxygen consumption (V. o2), but high ventilation. Group C had an increased risk (hazard ratio, 1.3; TAPSE ≥ 16 mm, PASP ≥ 40 mm Hg), a reduced peak V. o2, and a high EOV prevalence. Group D had the highest risk (hazard ratio, 5.6), the worse RV-pulmonary pressure coupling (TAPSE < 16 and PASP ≥ 40 mm Hg), the lowest peak V. o2, and the highest EOV rate.

CONCLUSIONS:  TAPSE/PASP, combined with exercise ventilation, provides relevant clinical and prognostic insights into HF. A low TAPSE/PASP with EOV identifies patients at a particularly high risk of cardiac events.

Figures in this Article

Heart failure (HF) of both systolic and diastolic origin causes pulmonary hypertension (PH) through the increased upstream transmission of elevated pulmonary venous pressure and, in some patients, additional pulmonary vascular remodeling.14 In both cases, PH is associated with decreased survival in proportion to increased pulmonary artery pressure.58 The negative impact of PH on outcome in left ventricular (LV) failure (HF) is related mainly to a coexistent alteration in the indexes of the right ventricular (RV) function.6,912

The right ventricle basically adapts to increased afterload by an increased contractility. When systolic function adaptation fails, the right ventricle becomes uncoupled from the pulmonary circulation and dilates to preserve flow output at the price of systemic congestion.13 The right ventricle in HF is exposed to early uncoupling because of the loss of positive systolic interaction with the left ventricle and/or the extension of the LV disease process to RV myocardial tissue.1,14 A combination of noninvasive measurements of systolic function and pulmonary artery pressure to estimate RV-arterial coupling may be of functional and prognostic relevance.10 We reported that the evaluation of the RV functional state by using the relationship between the tricuspid annular plane systolic excursion (TAPSE) and the pulmonary artery systolic pressure (PASP) as a surrogate for the RV length-force relationship is of clinical and prognostic relevance.10 In particular, in a cohort of patients with HF with both reduced and preserved ejection fraction (EF), assessing TAPSE vs PASP as a simple ratio led to an improved prognostic prediction when compared with assessing either variable separately. A TAPSE/PASP ratio (TAPSE/PASP) ≤ 0.36 mm/mm Hg identified patients with HF who were at a very high risk irrespective of reduced or preserved EF.10

Cardiopulmonary exercise testing (CPET) is essential to the assessment of functional impairment and prognosis in HF.15 Patients with HF typically present with a decreased peak oxygen consumption (V. o2) but, even more importantly, an increased minute ventilation (V. e) at any level of metabolic rate, best measured by the V. e/CO2 production (V. co2) slope.16,17 Furthermore, it has been shown that the presence of exercise oscillatory ventilation (EOV) is an ominous prognostic indicator that is even more accurate than the V. e/V. co2 slope.18,19

Based on these premises, we aimed to expand the significance of TAPSE/PASP and studied the associations between echocardiographic measures of right-sided heart function and the ventilatory response assessed by CPET, hypothesizing that differences in exercise ventilation assessed by exercise gas exchange analysis would relate primarily to metrics of the right-sided heart reserve in this population.

Patients

From March 2005 to September 2010, 459 consecutive patients with known HF were screened for study enrollment at the time of referral for a clinically indicated hemodynamic and functional assessment. The patients were enrolled at two centers, the Cardiopulmonary Laboratory at San Paolo Hospital, Milan, Italy, and the Cardiac Rehabilitation Institute at Fondazione Maugeri, Veruno, Italy.

The subjects underwent a two-dimensional echocardiographic/Doppler evaluation and CPET. Inclusion criteria were (1) signs and symptoms of HF and (2) adequate echocardiographic windows. The diagnosis of HF was based on the National Health and Nutrition Examination Survey (NHANES) congestive heart failure criteria score20; patients were considered to have a preserved EF when the LV ejection fraction (LVEF) was ≥ 50% and the additional criteria proposed by the European Society of Cardiology criteria21 were fulfilled.

The recruited patients were monitored in this prospective observational study, which was approved by the local ethical institutional review board at each institute (San Paolo approval number 09/04 and Fondazione Maugeri approval number 2005). Informed consent was obtained from all subjects prior to enrollment.

Event Tracking and End Points

The subjects were followed for major cardiac events (cardiac mortality, LV assist device implant, or heart transplant) via hospital and outpatient medical chart review for up to 4 years following data collection. They were followed by the HF program at the two institutions included in this analysis, which provided a high likelihood that all events were captured.

Echocardiography: TAPSE and PASP Measurements

Echocardiographic imaging was performed using a Philips IE33 and a 5.2-MHz transducer (Philips Medical Systems). In both centers, an experienced cardiologist obtained echocardiographic measures according to current guidelines.

A two-dimensional Doppler examination was performed using a prespecified echocardiographic protocol using views specifically designed to optimize RV imaging. To obtain TAPSE, the apical four-chamber view was used and an M-mode cursor was placed through the lateral tricuspid annulus in real time. Offline, the brightness was adjusted to maximize the contrast between the M-mode signal arising from the tricuspid annulus and the background. TAPSE was measured as the total displacement of the tricuspid annulus (millimeters) from end-diastole to end-systole, with values representing TAPSE being averaged over three to five beats.22

PASP was estimated by Doppler echocardiography from the systolic RV to the right atrial pressure gradient using the modified Bernoulli equation. Right atrial pressure (assessed jugular venous pressure) was added to the calculated gradient to yield PASP.23 No subjects had significant RV outflow tract obstruction. Interobserver variability, assessed in a sample size of 20% of the total population, was 3.5% and 3.4% for mono- and bidimensional echocardiography, respectively, and 4.7% and 4.3% for Doppler variables in the two centers, respectively.

CPET Procedures

Symptom-limited CPET was performed on a bicycle ergometer for all subjects. Pharmacologic therapy was maintained during CPET. Individualized ramp protocols were designed to obtain a duration of between 8 and 10 min. Ventilatory expired gas analysis was performed using a Sensormedics metabolic cart (Vmax). Before each test, the equipment was calibrated using reference gases according to the manufacturer’s specifications.

Standard 12-lead ECGs were obtained at rest, at each minute during exercise, and for at least 5 min during the recovery phase; BP was measured using a standard cuff sphygmomanometer. Heart rate was determined at rest, at peak exercise, and at 1 min of recovery. An active cool-down period for at least 1 min was used for all tests. In addition, V. e, V. o2, and V. co2 were acquired breath by breath, averaged over 30 s, and printed using rolling averages every 10 s. The V-slope method was used to measure the anaerobic threshold.24 Peak V. o2 and peak respiratory exchange ratio were expressed as the highest 10-s averaged sample obtained during the last 20 s of testing. V. e and V. co2 values, acquired from the initiation of exercise to peak, were input into spreadsheet software (Microsoft Excel; Microsoft Corporation) to calculate the V. e/V. co2 slope via least-squares linear regression (y = mx + b, m = slope).

EOV during CPET has been described in detail previously.19,25 Briefly, the criteria for EOV included the presence of three or more regular oscillatory fluctuations in V. e with a minimal average amplitude of 5 L/min persisting for at least 60% of the entire exercise. Test termination criteria consisted of symptoms (ie, dyspnea and/or fatigue), ventricular tachycardia, > 2 mm of horizontal or downsloping ECG ST segment depression, or a drop in systolic BP of > 20 mm Hg during progressive exercise. A qualified exercise physiologist conducted each exercise test with physician supervision.

Statistical Analysis

Statistical software packages (SPSS version19.0 [SPSS Inc] and R [http://www.r-project.org/]) were used to perform all analyses. Continuous and categorical data are reported as mean ± SD and percentages, respectively. Independent Student t tests were used to assess differences in clinical, tissue Doppler echocardiography, and CPET variables between patient subgroups according to event status. Independent Student t tests were also used to assess differences in key Doppler echocardiography variables according to the presence or absence of EOV. Differences in categorical data were tested by χ2 analysis. A four-quadrant approach using TAPSE and PASP was built up according to a TAPSE and PASP threshold of < 16 mm or ≥ 16 mm and < 40 mm Hg or ≥ 40 mm Hg, respectively.

A one-way analysis of variance (ANOVA) was used to assess differences in the V. e/V. co2 slope and peak V. o2 according to these thresholds, and the prevalence of EOV was assessed by χ2 analysis. Differences in TAPSE/PASP according to the ventilatory16 and Weber26 classification systems were assessed by the ANOVA test.

A Tukey test was used for post hoc analysis once significant differences emerged at ANOVA. The relationship between key Doppler echocardiography and CPET variables was tested by the Pearson product moment correlation. A life table was used to determine the annual major cardiac event rate. Univariate and multivariate (forward stepwise method; entry and removal value of 0.05 and 0.10, respectively) Cox regression analysis was used to assess the prognostic value of key clinical, tissue Doppler echocardiography, and CPET variables. Because of colinearity issues among TAPSE, PASP, and TAPSE/PASP, the expression with the highest χ2 value and concordance index in the univariate Cox regression analysis was included in the multivariate analysis. Kaplan-Meier analysis was used to assess the differences in survival among subjects according to the dichotomous classification of variables retained in the Cox multivariate regression analysis. The dichotomous threshold value for TAPSE/PASP used in this study was established in a previous analysis.10

Statistical significance among the risk categories for all Kaplan-Meier analyses was determined by the log-rank test. A P value < .05 was considered statistically significant for all tests.

Seventy major cardiac events (62 deaths, four LV assist device implants, and four heart transplants) took place during the 4-year tracking period. The annual event rate was 7.1%. Table 1 lists the demographic and hemodynamic variables according to major cardiac event status. Ten percent of patients had HF-preserved EF.

Table Graphic Jump Location
TABLE 1 ]  Differences in Key Variables According to Survival Status

CRT = cardiac resynchronization therapy; EOV = exercise oscillatory ventilation; HF = heart failure; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PASP = pulmonary artery systolic pressure; RAS = renin angiotensin system; TAPSE = tricuspid annular plane systolic excursion; TAPSE/PASP = tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio; V. e/V. co2 = minute ventilation/CO2 production; V. o2 = oxygen consumption.

Clinical characteristics were similar among subgroups except for New York Heart Association (NYHA) classification, which was significantly higher in subjects who died during the tracking period. Doppler and tissue Doppler imaging echocardiography and CPET measures were significantly worse in subjects who suffered a major cardiac event than in those who were event free during the tracking period.

Table 2 reports the univariate and multivariate Cox regression analyses. NYHA class and all Doppler echocardiography and CPET variables were significant predictors of major cardiac events. TAPSE/PASP demonstrated the highest univariate χ2 value. Moreover, the concordance index was highest for TAPSE/PASP (0.79 [SE = 0.037]), followed by PASP (0.76 [SE = 0.037]) and TAPSE (0.74 [SE = 0.037]). In the multivariate analysis, TAPSE/PASP was the strongest predictor, whereas NYHA class and EOV added significant predictive value. Figure 1 illustrates survival characteristics according to TAPSE/PASP quartiles. Subjects in the highest quartile had no events, whereas those in the lowest quartile were at significantly higher risk. Subjects in the middle quartiles were at intermediate and comparable risk.

Table Graphic Jump Location
TABLE 2 ]  Survival Analysis for Key Clinical, Tissue Doppler Echocardiography, and Cardiopulmonary Exercise Testing Variables

See Table 1 legend for expansion of abbreviations.

a 

Residual χ2.

b 

Retained in multivariate regression.

Figure Jump LinkFigure 1 –  Kaplan-Meier analysis according to TAPSE/PASP quartiles.Grahic Jump Location

Kaplan-Meier analysis (Fig 2) was performed using dichotomous thresholds for these three variables. As the number of unfavorable responses increased from zero to three, the likelihood of a major cardiac event clearly increased.

Figure Jump LinkFigure 2 –  Kaplan-Meier analysis for variables retained in the multivariate Cox regression.Grahic Jump Location

As reported in Table 3, the Pearson product moment documented a correlation between Doppler echocardiography and CPET variables. Both peak V. o2 and the V. e/V. co2 slope were significantly correlated with TAPSE, PASP, and TAPSE/PASP. Only the V. e/V. co2 slope was significantly correlated with LVEF, and this relationship was substantially weaker. Correlations were significant but low in accordance with the large number of subjects investigated.

Table Graphic Jump Location
TABLE 3 ]  Pearson Product Moment Correlation Analysis Between Key Doppler Echocardiography and CPET Variables

CPET = cardiopulmonary exercise testing. See Table 1 legend for expansion of other abbreviations.

a 

P < .001.

Table 4 lists comparisons of key Doppler echocardiography variables according to the presence or absence of EOV. LVEF was not significantly different according to EOV status. TAPSE and PASP were respectively lower and higher in subjects with EOV. TAPSE/PASP was significantly different among all ventilatory classification subgroups (Fig 3A). Once grouped according to the Weber classification, TAPSE/PASP was similar between class A and class B, but significantly different among all other groups (Fig 3B). TAPSE and TAPSE/PASP (Fig 3C) were significantly lower, and PASP was significantly higher, in subjects who demonstrated EOV during CPET (Table 4). Figure 4 illustrates differences in peak V. o2, the V. e/V. co2 slope, and EOV prevalence when the population was divided according to a TAPSE and PASP threshold of < 16 mm or ≥ 16 mm and < 40 mm Hg or ≥ 40 mm Hg, respectively. Four groups (A-D) were identified with several significant differences in key CPET variables as to the four-quadrant distribution. In group A (TAPSE > 16 mm and PASP < 40 mm Hg), patients exhibited the best physical performance and ventilation. In group B, patients had normal PASP (< 40 mm Hg) and some degree of RV systolic dysfunction (TAPSE < 16 mm), a preserved overall exercise performance, but initially impaired ventilation efficiency. Group C was composed of those patients who maintained a compensatory increase in longitudinal RV fractional shortening (TAPSE > 16 mm) in response to increased PASP (> 40 mm Hg), with a compromised exercise phenotype, especially exhibiting EOV at a high rate. Group D was composed of patients who were more compromised, with the worse RV-pulmonary pressure uncoupling (TAPSE < 16 mm and PASP > 40 mm Hg), lower overall exercise performance, and highest V. e/V. co2 slope and EOV rate.

Table Graphic Jump Location
TABLE 4 ]  Comparison of Key Doppler Echocardiography Variables According to Absence/Presence of EOV

See Table 1 legend for expansion of abbreviations.

Figure Jump LinkFigure 3 –  Difference in TAPSE/PASP. A, According to the Weber classification.26 B, According to the VC System.16 C, According to the absence or presence of EOV. VC = ventilatory classification. See Figure 2 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4 –  Peak VO2 in groups A and B was significantly different from that in groups C and D. VE/VCO2 slope in group A was significantly different from that in groups C and D, and VE/VCO2 slope in group D was significantly different from that in all other groups. EOV in groups A and B was significantly different from that in groups C and D, and EOV in group C was significantly different from that in group D. VCO2 = carbon dioxide production; VE = minute ventilation; VO2 = oxygen consumption. See Figure 2 and 3 legends for expansion of other abbreviations.Grahic Jump Location

The current results show that a simple echocardiographic assessment of RV-arterial coupling by TAPSE/PASP is of added value to EOV and NYHA classification for the prognostication of HF. PH indicates a poor prognosis in HF,17 especially when the right ventricle fails.14,6,912 The right ventricle normally adapts to increased afterload by an increased contractility. Failure of this “homeometric adaptation” leads to a progressively increased use of Starling’s “heterometric adaptation” (ie, preservation of stroke volume though increased end-diastolic volume).12 At this stage, patients with PH suffer from a decreased exercise capacity because of a decreased adapted increase in cardiac output, and from congestion because of increased ventricular filling pressures.13 Gold standard assessments of the adequacy of the coupling of RV function to the pulmonary circulation, based on instantaneous pressure and volume measurements, have been validated13 but are invasive and impractical in clinical practice. We, therefore, designed a noninvasive approach based on TAPSE as a measure of contractility and PASP as a measure of afterload.10 We showed previously that these measurements are easy to apply in daily clinical practice and, expressed as TAPSE/PASP, may be of major functional and prognostic relevance.10 This was confirmed in the current study. TAPSE/PASP showed up as an independent predictor of event-free survival, with a value < 0.35 mm/mm Hg indicating a particularly poor prognosis.

CPET is another noninvasive approach that is very useful in the evaluation of disease severity in HF.16,25,26 Several studies have drawn attention to the relevance of EOV, in addition to decreased peak V. o2 and increased V. e/V. co2 slope, as an important risk of premature death in HF.18,19,25 Increased ventilation in HF is attributable to a combination of increased dead space and chemosensitivity.16,25,27,28 The cause of EOV in HF remains unclear, and multiple explanations have been provided.15 A predominant theory suggests that EOV is related to the distension and dysfunction of the right-sided heart chambers and occurs as a consequence of fluctuations in cardiac output and some circulatory transit time delay caused by RV failure.2933 The current findings fully support these observations, showing a significantly greater burden of right-sided heart disease in the group of patients with an EOV compared with those with no EOV.

When TAPSE/PASP was considered as a continuous variable, it showed a powerful ability to predict risk. We proposed a four-quadrant-format patients’ distribution based on cutoff of RV function (TAPSE, 16 mm) and pulmonary pressure (PASP, 40 mm Hg). The dichotomous analysis performed under the four-quadrant approach expanded on the significance of the ratio unmasking different phenotypes and optimizing the use of the TAPSE vs PASP combination. For example, consider two cases leading to the same TAPSE/PASP of 0.31: one subject with a TAPSE of 14 mm and a PASP of 44 mm Hg and the other with a TAPSE of 18 mm and a PASP of 58 mm Hg. A different level of risk may be defined, with the former case being in group B (hazard ratio, 0.88) and the latter in group C (hazard ratio, 1.3) quadrants. Similarly, the pattern of CPET variables, especially EOV rate, was consistently worse in group C. Collectively, this information suggests that the four-quadrant approach may help allocate the single patient to a definitive risk group, also making it possible to identify a closed “cross talk” between functional performance and the RV-pulmonary pressure phenotype.

Because our study was performed in a relatively large cohort of patients with HF with variable disease severity and was not confined to patients with documented left-sided PH, the findings may have broad applicability, especially to those HF populations that, despite a preserved overall exercise performance and ventilator response, may manifest some early abnormalities in RV function as suggested by TAPSE/PASP. This may be the case when considering patients in group B according to the proposed four-quadrant distribution of right-sided heart and CPET-derived variables. Interestingly, these patients initially exhibited a reduced RV longitudinal function (TAPSE < 16 mm) within a normal range of PASP (< 40 mm Hg), maintaining a still favorable exercise phenotype, with an intermediate peak V. o2, a V. e/V. co2 slope at the upper limits of normalcy, and a low rate of EOV. This may have multiple explanations, such as an abnormal lung volume pattern with restriction; alternatively, in this group of patients, there was most likely a predominance of subjects with RV myopathy but without significant PH.

Our study has the intrinsic limitation that RV function, especially PASP, was estimated noninvasively. Nonetheless, the wide population investigated and the long follow-up provide a solid basis for further validation of our findings in right-sided heart catheterization studies with smaller and well-selected populations. Furthermore, PASP is an imperfect measure of RV afterload that, by definition, captures components of both vascular resistance and pulmonary venous congestion. However, given that abnormalities of each component of load are synergically unfavorable in chronic HF, it follows that PASP retains prognostic significance herein. Another potential limitation is the lack of any interventional assessment to determine whether TAPSE/PASP is responsive to specific interventions that are likewise effective on the CPET response.

In conclusion, the current findings support a central role of echo-derived variables in identifying right-sided heart dysfunction in HF and suggest that the easy-to-perform approach of normalizing TAPSE/PASP provides relevant clinical and prognostic insights that are associated with the CPET response. Specifically, the presence of a low TAPSE/PASP and EOV could serve as an indicator of very high risk and as a target condition to more closely monitor. It may also encourage more aggressive management of patients with HF.

Author contributions: M. G. is the guarantor of the entire manuscript. M. G. contributed to the conceptual framework and manuscript writing; U. C., F. B., and P. T. contributed to the data collection; R. A. contributed to the data analysis; L. P. C. contributed to the statistical analysis; R. N., R. A., U. C., S. G., P. F., A. R., L. P. C., F. B., and P. T. contributed to the manuscript revision.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Ghio has participated in speaking activities for GlaxoSmithKline, Actelion Pharmaceuticals Ltd, and Pfizer Inc. Dr Forfia has served as a consultant to Actelion Pharmaceuticals Ltd and Bayer. Drs Guazzi, Naeije, Arena, Corrà, Rossi, Cahalin, Bandera, and Temporelli have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

ANOVA

analysis of variance

CPET

cardiopulmonary exercise testing

EF

ejection fraction

EOV

exercise oscillatory ventilation

HF

heart failure

LV

left ventricular

LVEF

left ventricular ejection fraction

NYHA

New York Heart Association

PASP

pulmonary artery systolic pressure

PH

pulmonary hypertension

RV

right ventricular

TAPSE

tricuspid annular plane systolic excursion

TAPSE/PASP

tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio

V. co2

CO2 production

V. e

minute ventilation

V. o2

oxygen consumption

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Guazzi M, Arena R, Ascione A, Piepoli M, Guazzi MD; Gruppo di Studio Fisiologia dell’Esercizio, Cardiologia dello Sport e Riabilitazione Cardiovascolare of the Italian Society of Cardiology. Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value. Am Heart J. 2007;153(5):859-867. [CrossRef] [PubMed]
 
Weber KT, Janicki JS, McElroy PA. Determination of aerobic capacity and the severity of chronic cardiac and circulatory failure. Circulation. 1987;76(6 pt 2):VI40-VI45. [PubMed]
 
Wasserman K, Zhang YY, Gitt A, et al. Lung function and exercise gas exchange in chronic heart failure. Circulation. 1997;96(7):2221-2227. [CrossRef] [PubMed]
 
Johnson RL Jr. Gas exchange efficiency in congestive heart failure II. Circulation. 2001;103(7):916-918. [CrossRef] [PubMed]
 
Methvin AB, Owens AT, Emmi AG, et al. Ventilatory inefficiency reflects right ventricular dysfunction in systolic heart failure. Chest. 2011;139(3):617-625. [CrossRef] [PubMed]
 
Lewis GD, Shah RV, Pappagianopolas PP, Systrom DM, Semigran MJ. Determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone. Circ Heart Fail. 2008;1(4):227-233. [CrossRef] [PubMed]
 
Murphy RM, Shah RV, Malhotra R, et al. Exercise oscillatory ventilation in systolic heart failure: an indicator of impaired hemodynamic response to exercise. Circulation. 2011;124(13):1442-1451. [CrossRef] [PubMed]
 
Guazzi M. Treating exercise oscillatory ventilation in heart failure: the detail that may matter. Eur Respir J. 2012;40(5):1075-1077. [CrossRef] [PubMed]
 
Guazzi M, Boracchi P, Arena R, et al. Development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE) study. J Card Fail. 2010;16(10):799-805. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Kaplan-Meier analysis according to TAPSE/PASP quartiles.Grahic Jump Location
Figure Jump LinkFigure 2 –  Kaplan-Meier analysis for variables retained in the multivariate Cox regression.Grahic Jump Location
Figure Jump LinkFigure 3 –  Difference in TAPSE/PASP. A, According to the Weber classification.26 B, According to the VC System.16 C, According to the absence or presence of EOV. VC = ventilatory classification. See Figure 2 legend for expansion of other abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4 –  Peak VO2 in groups A and B was significantly different from that in groups C and D. VE/VCO2 slope in group A was significantly different from that in groups C and D, and VE/VCO2 slope in group D was significantly different from that in all other groups. EOV in groups A and B was significantly different from that in groups C and D, and EOV in group C was significantly different from that in group D. VCO2 = carbon dioxide production; VE = minute ventilation; VO2 = oxygen consumption. See Figure 2 and 3 legends for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Differences in Key Variables According to Survival Status

CRT = cardiac resynchronization therapy; EOV = exercise oscillatory ventilation; HF = heart failure; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PASP = pulmonary artery systolic pressure; RAS = renin angiotensin system; TAPSE = tricuspid annular plane systolic excursion; TAPSE/PASP = tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio; V. e/V. co2 = minute ventilation/CO2 production; V. o2 = oxygen consumption.

Table Graphic Jump Location
TABLE 2 ]  Survival Analysis for Key Clinical, Tissue Doppler Echocardiography, and Cardiopulmonary Exercise Testing Variables

See Table 1 legend for expansion of abbreviations.

a 

Residual χ2.

b 

Retained in multivariate regression.

Table Graphic Jump Location
TABLE 3 ]  Pearson Product Moment Correlation Analysis Between Key Doppler Echocardiography and CPET Variables

CPET = cardiopulmonary exercise testing. See Table 1 legend for expansion of other abbreviations.

a 

P < .001.

Table Graphic Jump Location
TABLE 4 ]  Comparison of Key Doppler Echocardiography Variables According to Absence/Presence of EOV

See Table 1 legend for expansion of abbreviations.

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Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984;70(4):657-662. [CrossRef] [PubMed]
 
Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol (1985). 1986;60(6):2020-2027. [PubMed]
 
Guazzi M, Arena R, Ascione A, Piepoli M, Guazzi MD; Gruppo di Studio Fisiologia dell’Esercizio, Cardiologia dello Sport e Riabilitazione Cardiovascolare of the Italian Society of Cardiology. Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value. Am Heart J. 2007;153(5):859-867. [CrossRef] [PubMed]
 
Weber KT, Janicki JS, McElroy PA. Determination of aerobic capacity and the severity of chronic cardiac and circulatory failure. Circulation. 1987;76(6 pt 2):VI40-VI45. [PubMed]
 
Wasserman K, Zhang YY, Gitt A, et al. Lung function and exercise gas exchange in chronic heart failure. Circulation. 1997;96(7):2221-2227. [CrossRef] [PubMed]
 
Johnson RL Jr. Gas exchange efficiency in congestive heart failure II. Circulation. 2001;103(7):916-918. [CrossRef] [PubMed]
 
Methvin AB, Owens AT, Emmi AG, et al. Ventilatory inefficiency reflects right ventricular dysfunction in systolic heart failure. Chest. 2011;139(3):617-625. [CrossRef] [PubMed]
 
Lewis GD, Shah RV, Pappagianopolas PP, Systrom DM, Semigran MJ. Determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone. Circ Heart Fail. 2008;1(4):227-233. [CrossRef] [PubMed]
 
Murphy RM, Shah RV, Malhotra R, et al. Exercise oscillatory ventilation in systolic heart failure: an indicator of impaired hemodynamic response to exercise. Circulation. 2011;124(13):1442-1451. [CrossRef] [PubMed]
 
Guazzi M. Treating exercise oscillatory ventilation in heart failure: the detail that may matter. Eur Respir J. 2012;40(5):1075-1077. [CrossRef] [PubMed]
 
Guazzi M, Boracchi P, Arena R, et al. Development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE) study. J Card Fail. 2010;16(10):799-805. [CrossRef] [PubMed]
 
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