Author + information
- Jennifer T. Thibodeau, MD, MSc,
- Aslan T. Turer, MD, MHS,
- Sarah K. Gualano, MD,
- Colby R. Ayers, MS,
- Mariella Velez-Martinez, MD,
- Joseph D. Mishkin, MD,
- Parag C. Patel, MD,
- Pradeep P.A. Mammen, MD,
- David W. Markham, MD, MSc,
- Benjamin D. Levine, MD and
- Mark H. Drazner, MD, MSc∗ ()
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
- ↵∗Reprint requests and correspondence:
Dr. Mark H. Drazner, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9047.
Objectives This study sought to examine the frequency and hemodynamic correlates of shortness of breath when bending forward, a symptom we have termed “bendopnea.”
Background Many heart failure patients describe bendopnea such as when putting on their shoes. This symptom has not previously been characterized.
Methods We conducted a prospective study of 102 subjects with systolic heart failure referred for right-heart catheterization. Time to onset of bendopnea was measured prior to catheterization. Forty-six subjects also underwent hemodynamic assessment when sitting and bending. Hemodynamic profiles were assigned on the basis of whether pulmonary capillary wedge pressure (PCWP) was ≥22 mm Hg and cardiac index (CI) was ≤2.2 l/min/m2.
Results Bendopnea was present in 29 of 102 (28%) subjects with median (25th, 75th percentiles) time to onset of 8 (7, 11) seconds. Subjects with bendopnea had higher supine right atrial pressure (RAP) (p = 0.001) and PCWP (p = 0.0004) than those without bendopnea but similar CI (p = 0.2). RAP and PCWP increased comparably in subjects with and without bendopnea when bending, but CI did not change. In those with, versus without, bendopnea, there was more than a 3-fold higher frequency of a supine hemodynamic profile consisting of elevated PCWP with low CI (55% vs. 16%, respectively, p < 0.001) but no association with a profile of elevated PCWP with normal CI (p = 0.95).
Conclusions Bendopnea is mediated via a further increase in filling pressures during bending when filling pressures are already high, particularly if CI is reduced. Awareness of bendopnea should improve noninvasive assessment of hemodynamics in subjects with heart failure.
Shortness of breath, a dominant symptom in patients with heart failure, is subclassified on the basis of the activity that provokes its onset. Dyspnea with exertion, orthopnea and paroxysmal nocturnal dyspnea, criteria used to define heart failure by the Framingham Heart Study in 1971 (1), continue to be used in routine clinical practice to classify breathlessness. Recently, we have noticed that many heart failure patients describe shortness of breath specifically when bending forward, such as when putting on their shoes or socks. To our knowledge, this symptom has not previously been characterized. In order to determine the potential mechanism and clinical implications of this symptom, we conducted the present prospective study to examine the frequency and hemodynamic correlates of shortness of breath when bending forward, or “bendopnea,” in heart failure patients with systolic dysfunction who were referred for right heart catheterization.
Study design and subject selection
We conducted a single-center prospective observational study of a convenience sample of 102 subjects with systolic heart failure who were referred for right heart catheterization at the University of Texas Southwestern Medical Center for clinical indications between June 2010 and May 2012. Inpatient or outpatient subjects 18 years of age or older with systolic heart failure, defined as a left ventricular ejection fraction (LVEF) ≤40% within the previous 3 months, were eligible for enrollment. Subjects were excluded if they had undergone cardiac transplantation or required mechanical circulatory support with an intra-aortic balloon pump or ventricular assist device. The study protocol was reviewed and approved by the institutional review board. All subjects gave written informed consent.
A history and physical examination were completed for each subject by an investigator within 6 h prior to right-heart catheterization. Data collected included demographic data, medical history, cardiac medications, etiology of cardiomyopathy, peak oxygen consumption, LVEF determined within 3 months of enrollment, and assessment of functional status by New York Heart Association (NYHA) classification system (2). In order to determine the presence of bendopnea, each subject sat in a chair and bent forward at the waist as if putting on their socks or shoes, while an investigator timed the duration to the onset of shortness of breath, as stated to the patient “tell me when you feel short of breath.” While some patients reported lightheadedness or fullness of the head, chest, or abdomen, the symptom that we describe as bendopnea is specifically shortness of breath when bending forward. This maneuver was performed after consent was obtained but prior to the subject entering the catheterization suite. The subject was classified as having bendopnea if they reported shortness of breath within 30 sec of bending. In addition, subjects were queried regarding the presence of the following symptoms within 7 days prior to enrollment: angina, dyspnea on exertion (if present, the number of blocks before symptom onset), orthopnea, paroxysmal nocturnal dyspnea, weight gain, lower extremity swelling, abdominal fullness or pressure, early satiety, nausea or vomiting, palpitations, syncope, and defibrillator firing. Physical examination included height, weight, and body mass index (BMI) on the day of enrollment as recorded in the clinical chart, measurement of waist and hip circumference, estimation of jugular venous pressure (JVP), and assessment of the presence of a third heart sound, rales, and lower extremity edema. Laboratory values from the clinical chart were recorded if they were within 1 week of enrollment and included hemoglobin, creatinine, and natriuretic peptide concentration. Estimated glomerular filtration rate was determined by the Modification of Diet in Renal Disease equation (3). Due to a change in assay availability at our institution, B-type natriuretic peptide concentrations were measured in the first 54 subjects, whereas subsequent subjects had N-terminal pro-B-type natriuretic peptide concentrations measured.
Interventional cardiologists who were blinded to the results of the clinical assessment and determination of bendopnea status performed the right-heart catheterization. All enrolled subjects underwent routine right-heart catheterization while lying in the supine position. Beat-by-beat arterial blood pressure measurements were taken by using finger photoplethysmography (Finapres, Ohmeda, Englewood, Colorado), and heart rate was determined from a 3-lead electrocardiogram. Dual pressure transducers were used to allow simultaneous measurement of right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP). The mean pressures were used for the RAP and PCWP. The PCWP was confirmed by oxygen saturation in two-thirds of subjects and by waveform inspection in the remaining cases. All pressure measurements were obtained at end expiration. Cardiac output was obtained using both the thermodilution and the Fick methods. For the Fick equation, oxygen consumption was estimated according to the derived formula programmed into the Xper Flex Cardio (Philips, Andover, Massachusetts) physiomonitoring system (4) used in our catheterization suite, as follows: VO2 (ml/min) = 133 ml/min/m2 × body surface area (m2), where body surface area was calculated according to the formula of Dubois and Dubois (5): [0.007184 × weight (kg)0.425 × height (cm)0.725]. Thermodilution cardiac output measurements were obtained at least in triplicate and averaged such that all included values were within 10% of the mean. Cardiac index (CI) was calculated as the cardiac output indexed to body surface area.
Measurements When Sitting and Bending
A subset of the cohort who consented to additional measurements (n = 46) also underwent hemodynamic assessment when sitting upright in a chair and when sitting in a chair while bending forward at the waist. Location of the right atrial site was determined under fluoroscopy at the beginning of the catheterization procedure, and the corresponding skin site was marked for leveling purposes. After completion of the standard supine right-heart catheterization, subjects were moved to a chair and repeat assessment of hemodynamics was performed after releveling of the pressure transducers and at least 2 min of rest. The subjects then bent forward at the waist as if tying their shoes and underwent repeat hemodynamic assessment after releveling of the pressure transducers and at least 1 min of bending. The presence of bendopnea was also reassessed at this time.
Subjects were classified into 1 of 4 hemodynamic profiles, as advocated by other investigators (6), based on the basis of invasively-measured left ventricular filling pressures and CI: profile A, “warm and dry”: CI >2.2 l/min/m2, PCWP <22 mm Hg; profile B, “warm and wet”: CI >2.2 l/min/m2, PCWP ≥22 mm Hg; profile C, “cold and wet”: CI ≤2.2 l/min/m2, PCWP ≥22 mm Hg; and profile L, “cold and dry”: CI ≤2.2 l/min/m2, PCWP <22 mm Hg.
We estimated that 30% of enrolled subjects would have bendopnea. Given this proportion, a total of 100 subjects would allow a power of 90% to detect a 5 mm Hg change in RAP and PCWP, assuming a standard deviation of 7 (7); and a power of over 95% to detect a 0.5 l/min/m2 change in CI, assuming a standard deviation of 0.6 (7). Descriptive statistics are reported as median (25th, 75th percentiles) or as numbers (%), as appropriate. The chi-square test (categorical variables) and the Wilcoxon rank sum test (continuous variables) were used for comparison of clinical characteristics of the bendopnea and the no-bendopnea groups. In cases of low cell counts, the Fisher's exact test was used for comparison of the categorical variables. For the primary outcome of differences in hemodynamic parameters when supine, the Wilcoxon rank sum test was used to compare the median values between subjects with and without bendopnea. The Wilcoxon rank sum test was also used to compare the median values of the hemodynamic parameters of those with and without bendopnea at each position and to assess comparisons in the change in hemodynamics across supine, sitting, and bending positions. Statistical significance was set at 0.05, and all tests were 2-tailed. Statistical analyses were conducted using SAS version 9.2 software (SAS Institute, Inc., Cary, North Carolina).
Bendopnea was present in 29 of 102 (28%) subjects. In those with bendopnea, the median (25th, 75th percentiles) time to symptom onset was 8 (7, 11) seconds. The clinical characteristics of subjects with and without bendopnea are summarized in Table 1. Most subjects were white, male, 60 to 65 years of age, and NYHA functional classes III and IV, with an LVEF of approximately 20%. Most subjects were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics. Subjects with bendopnea were more likely to have other symptoms of decompensated heart failure, including angina, dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and abdominal fullness or pressure. BMI was higher in subjects with bendopnea than in those without, but there were no differences in waist or hip circumferences and waist/hip ratios between these 2 groups. On physical examination, the only sign associated with bendopnea was an elevated JVP. There were no differences between subjects with and without bendopnea with respect to renal function, hemoglobin, and natriuretic peptide concentrations.
Supine hemodynamic findings
Supine hemodynamics for subjects with and without bendopnea are summarized in Table 2. Subjects with bendopnea had higher RAP and PCWP and lower pulmonary artery oxygen saturation and CI calculated using the Fick equation. There was no difference in the thermodilution CI between subjects with and without bendopnea (p = 0.17). Additionally, there were no difference in mean arterial pressure, heart rate, pulmonary vascular resistance (PVR), or systemic vascular resistance (SVR) between those with and without bendopnea.
Changes in hemodynamics with position
Of the 46 patients who underwent repeat hemodynamic assessment when bending, 16 (35%) had bendopnea and 30 (65%) did not (Online Table 1). Median RAP in subjects with bendopnea (compared to those without bendopnea) when sitting was 10 (6, 14) mm Hg versus 4 (2, 9) mm Hg, respectively (p = 0.02), and 19 (10, 26) mm Hg versus 12 (7, 18) mm Hg when bending, respectively (p = 0.07) (Fig. 1). This increase in RAP with bending was significant in both groups (p ≤ 0.0001 for both), but there was no difference in the amount of increase between these groups [11 (2, 15) mm Hg vs. 7 (3, 10) mm Hg, respectively, p = 0.24]. Subjects with bendopnea had higher median PCWP when sitting than those without [27 (19, 30) mm Hg vs. 13 (8, 22) mm Hg, respectively, p = 0.003] and also when bending [35 (29, 41) mm Hg vs. 22 (16, 35) mm Hg, respectively, p = 0.01]. As with RAP, PCWP increased when bending in subjects with and without bendopnea (p ≤ 0.0001 for both), but there was no difference in the amount of increase between these groups (p = 0.90). In contrast to the above findings, thermodilution CI did not differ between those with and those without bendopnea when sitting or bending (p = 0.34 and p = 0.42, respectively), nor did thermodilution CI change when bending either in subjects with or without bendopnea (p = 0.40). There were no differences in SVR or PVR between those with and those without bendopnea at all positions, and there were no changes in SVR or PVR with position change in either those with or without bendopnea (p > 0.05 for all).There was 100% agreement in bendopnea status assessed at study enrollment and during catheterization.
Mean arterial pressure, heart rate, SVR, PVR, transpulmonary gradient (mean PAP − PCWP) and transmural gradient (PCWP − RAP) (8–10) were similar in subjects with and without bendopnea at each position and did not significantly increase or decrease with position change (data not shown).
Distribution of hemodynamic profiles, stratified by bendopnea
As shown in Figure 2, subjects with bendopnea were predominantly hemodynamic profile C, whereas subjects without bendopnea were predominantly profiles A and L. To ensure that the increase in frequency of hemodynamic profile C and not profile B in those with bendopnea was not due to a higher PCWP in the former group, we compared the median PCWP values of these 2 profiles. Overall, the median PCWP in subjects who were profile B and C were similar [24 (22, 26) mm Hg and 25 (23, 28) mm Hg, respectively, p = 0.2]. Additionally, the median PCWPs were similar in profile B and C subjects with bendopnea [26 (24, 26) mm Hg and 25 (23, 29) mm Hg, respectively, p = 1.0] and without bendopnea [24 (22, 25) mm Hg and 27 (23, 28) mm Hg, respectively, p = 0.1]. The median increase in the PCWP with bending was 9 (2, 11) mm Hg in profile B subjects and 11 (6, 16) mm Hg in profile C subjects (p = 0.28).
Our study is the initial characterization of a novel symptom of heart failure, shortness of breath with bending forward, which we have termed bendopnea. Bendopnea was present in a sizable minority (approximately one-third) of the study cohort, was reproducible when reassessed later the same day, and was associated with hemodynamic derangements; specifically, elevated right ventricular and left ventricular filling pressures. Additionally, when subjects were categorized into 1 of 4 hemodynamic profiles on the basis of elevation of left ventricular filling pressures and adequacy of cardiac perfusion (6), we found that a profile of high PCWP with a low CI was significantly more common in those with bendopnea. Finally, by measuring ventricular filling pressures and CI in subjects when they bent forward, we found that bending led to an increase in ventricular filling pressures but no reduction in the cardiac index.
Previous studies have assessed the association of heart failure signs and symptoms with invasively measured hemodynamics. Orthopnea has been shown to be the symptom best correlated with elevated left ventricular filling pressures measured in the supine position (6,11,12). In the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness), orthopnea within the last week was associated strongly with very high PCWPs (e.g., 28 to 30 mm Hg) (11). In our current study, bendopnea (confirmed present on the day of the right heart catheterization) was also associated with elevated PCWP when measured in the supine and sitting positions and when subjects bent forward. Furthermore, orthopnea was 2-fold more common in those with bendopnea, a finding consistent with the hypothesis that both symptoms have the same underlying pathophysiological mechanism (i.e., elevated left ventricular filling pressures). As with symptoms, signs detected on physical examination also have been shown to be associated with elevated left ventricular filling pressures. In the ESCAPE trial, elevated JVP was the only physical examination finding associated with elevated PCWP (11). This finding is consistent with the present study where elevated JVP was the only physical examination finding associated with bendopnea (Table 1).
One of the objectives of the present study was to determine the pathophysiological basis of bendopnea. First, we wanted to confirm that bendopnea was not simply related to body habitus (i.e., increased abdominal girth). Although BMI was higher in those with bendopnea, we found there were no differences in waist circumference or waist/hip ratio in those with bendopnea, suggesting that increased abdominal girth was not the primary cause of bendopnea. Second, we wanted to determine whether bendopnea was related to elevated ventricular filling pressures or to a reduction in CI during bending. We found that subjects with bendopnea had higher ventricular filling pressures than those without, both in the supine and sitting positions. Furthermore, there was a significant increase in both right and left ventricular filling pressures during bending (Fig. 1), consistent with an increase in intrathoracic pressure. We interpret these data to suggest that during bending, increased intrathoracic pressure leads to a further increase in ventricular filling pressures, and subjects with bendopnea (who start with higher filling pressures) are more likely to reach a threshold pressure necessary to induce shortness of breath. We hypothesize that bendopnea is likely caused by elevation in the left-sided filling pressure, or PCWP, as has been demonstrated with other manifestations of shortness of breath in patients with heart failure (13–15). However, because right- and left-sided ventricular filling pressures often track together in patients with chronic heart failure (13–15), we cannot exclude with certainty the fact that further elevation of RAP also contributed to bendopnea. In contrast to the above-mentioned changes in filling pressures, we found that the CI as measured by the thermodilution method did not change significantly with bending, suggesting that a fall in CI with bending was not the cause of bendopnea. Nevertheless, a low CI appears to have some contributory role in this symptom given that hemodynamic profile C (elevated PCWP and low CI) but not profile B (elevated PCWP and adequate CI) was associated with bendopnea, even though the PCWP among those with profile C was no higher than those with profile B. However, we recognize that the number of subjects with profile B was relatively small in our study (n = 18) and that it may have been underpowered to detect an association with bendopnea.
Clinical implications of bendopnea
Assessing hemodynamics by history and physical examination is important both for prognostic and therapeutic purposes. Evidence of congestion has been shown to portend poor prognosis (16–21). For example, in a retrospective analysis of the SOLVD (Studies Of Left Ventricular Dysfunction) treatment trial, an elevated JVP was associated with a significantly increased risk of all-cause mortality, hospitalization for heart failure, and death from pump failure (17). Additionally, in those with advanced heart failure, lack of congestion at hospital discharge (11) or at a follow-up clinic visit after hospital discharge (22) was associated with improved outcomes. Thus, the prognostic utility of bendopnea should be assessed. In particular, bendopnea may have utility for physicians who are not adept at estimating jugular venous pressure.
The number of subjects enrolled was relatively small, particularly when assessing hemodynamics during postural changes. Nevertheless, we were able to document specific hemodynamic changes that occur with bending. We confirmed the PCWP with oxygen saturation in the supine but not sitting and bending positions. We estimated oxygen consumption rather than directly measuring it. However, having subjects breathe into a metabolic cart might have influenced their perception of bendopnea. The thermodilution method was used to measure cardiac output, and this approach can be inaccurate in low-output states or with severe tricuspid regurgitation or irregular rhythms (23). However, determination of cardiac output by thermodilution is used in clinical practice and forms the basis of routine medical decision making. Additionally, the thermodilution method was used in the National Heart, Lung, and Blood Institute-sponsored ESCAPE trial (7). Another limitation was that assessment of other symptoms of heart failure was by subject recall over the previous week and not determined on the day of their right-heart catheterization; thus, comparison of other symptoms of heart failure with bendopnea is limited. However, this was not the main focus of our study. Some patients with bendopnea did not have elevated PCWP, suggesting that factors other than elevated left ventricular filling pressures can cause this symptom. Nevertheless, our data show that in many patients, bendopnea is a marker of an elevated PCWP. We enrolled a convenience sample of patients that was based on the availability of the investigator and the cardiac catheterization laboratory to enroll research patients. However, the convenience sampling was due neither to the severity of illness nor the presence or absence of bendopnea. Our study cohort consisted of patients who were referred for right-heart catheterization, many of whom had advanced heart failure. As such, additional studies are needed to determine the prevalence of bendopnea among the general heart failure population.
Bendopnea, a newly described symptom in patients with heart failure, is mediated via a further increase in ventricular filling pressures during bending in subjects whose sitting ventricular filling pressures are already high, particularly in patients with low CI. Awareness of this symptom by physicians should improve their noninvasive assessment of hemodynamics in patients with heart failure.
For a supplemental table, please see the online version of this paper.
Dr. Markham has a financial relationship with Thoratec. Dr. Drazner has received support from the James M. Wooten Chair in Cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
This study was presented in part at the American Heart Association Scientific Sessions as part of the Samuel Levine Young Clinical Investigator Award session on November 3, 2012.
- Abbreviations and Acronyms
- body mass index
- cardiac index
- left ventricular ejection fraction
- jugular venous pressure
- New York Heart Association
- pulmonary capillary wedge pressure
- pulmonary vascular resistance
- right atrial pressure
- systemic vascular resistance
- Received July 19, 2013.
- Accepted July 25, 2013.
- American College of Cardiology Foundation
- Criteria Committee of the New York Heart Association
- ↵Philips Healthcare. Xper Flex Cardio Physiomonitoring System: Instructions for use. Andover, MA: 2011.
- Dubois D.,
- Dubois E.
- Nohria A.,
- Tsang S.W.,
- Fang J.C.,
- et al.
- Tyberg J.V.,
- Taichman G.C.,
- Smith E.R.,
- Douglas N.W.,
- Smiseth O.A.,
- Keon W.J.
- Drazner M.H.,
- Hellkamp A.S.,
- Leier C.V.,
- et al.
- Solomonica A.,
- Burger A.J.,
- Aronson D.
- Aaronson K.D.,
- Schwartz J.S.,
- Chen T.M.,
- Wong K.L.,
- Goin J.E.,
- Mancini D.M.
- Nishimura R.A.,
- Carabello B.A.