Chest Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vonk-Noordegraaf, A.
Right arrow Articles by Postmus, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vonk-Noordegraaf, A.
Right arrow Articles by Postmus, P. E.
(Chest. 2005;127:1898-1903.)
© 2005 American College of Chest Physicians

Early Changes of Cardiac Structure and Function in COPD Patients With Mild Hypoxemia*

Anton Vonk-Noordegraaf, MD, PhD, FCCP; J. Tim Marcus, PhD; Sebastiaan Holverda, MSc; Bea Roseboom, MD and Pieter E. Postmus, MD, PhD, FCCP

* From the Departments of Pulmonary Medicine (Drs. Vonk-Noordegraaf, Roseboom, Postmus, and Mr. Holverda) and Physics and Medical Technology (Dr. Marcus), Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, the Netherlands.

Correspondence to: Anton Vonk-Noordegraaf, MD, PhD, FCCP, Vrije Universiteit Medical Center, Department of Pulmonary Medicine, PO Box 7057, 1007 MB Amsterdam, the Netherlands; e-mail: A.Vonk{at}vumc.nl


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD patients with severe hypoxemia, little is known about these changes in patients with normoxia and mild hypoxemia.

Study objectives: To assess the structural and functional cardiac changes in COPD patients with normal PaO2 and without signs of RV failure.

Methods: In 25 clinically stable COPD patients (FEV1, 1.23 ± 0.51 L/s; PaO2, 82 ± 10 mm Hg [mean ± SD]) and 26 age-matched control subjects, the RV and left ventricular (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP) was estimated from right pulmonary artery distensibility.

Results: RV mass divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 ± 0.18 g/mL in the COPD group and 0.41 ± 0.09 g/mL in the control group (p < 0.01). LV and RV ejection fractions were 62 ± 14% and 53 ± 12% in the COPD patients, and 68 ± 11% and 53 ± 7% in the control subjects, respectively. PAP estimated from right pulmonary artery distensibility was not elevated in the COPD group.

Conclusion: From these results, we conclude that concentric RV hypertrophy is the earliest sign of RV pressure overload in patients with COPD. This structural adaptation of the heart does not alter RV and LV systolic function.

Key Words: COPD • cor pulmonale • hypoxemia • left ventricle • MRI • pulmonary hypertension • right ventricle • right ventricular hypertrophy • secondary pulmonary hypertension


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The classic view of the development of right ventricular (RV) hypertrophy in patients with COPD is that a reduction of the pulmonary vascular bed and hypoxia-induced pulmonary vasoconstriction increase pulmonary vascular resistance, leading to pulmonary hypertension. Clinical studies12 have shown that hypoxemia is one of the major determinants of pulmonary hypertension. Different patterns of hemodynamic abnormalities have been described in COPD. Patients with a severe obstructive ventilatory impairment but with relatively normal arterial blood gas values do not usually demonstrate pulmonary hypertension during rest. Patients with hypoxemia typically demonstrate pulmonary hypertension at rest accompanied by clinical and ECG evidence of RV hypertrophy.13 Postmortem findings provide further evidence of the relation between hypoxemia and the development of RV hypertrophy.4 Given these findings, it can be hypothesized that the adaptation mechanism of the RV is different in COPD patients without hypoxemia compared to patients with hypoxemia. Studies56 in large groups of patients with COPD and hypoxemia demonstrated increased RV volumes, decreased RV function, and impaired left ventricular (LV) diastolic function.

Advances in MRI have made it possible to accurately measure early changes of the complex geometry of the RV wall and chamber volume.7 In most MRI studies891011 in COPD, however, patients with severe hypoxemia were included. Therefore, no strong conclusions can be drawn from the early adaptation mechanisms of the RV in patients with normoxemia or mild hypoxemia and the consequences of any structural changes on RV and LV function. The objective of this study was to assess the early RV changes and the effect of these changes on both RV and LV function in a group of COPD patients with normoxemia compared to an age-matched control group of normal subjects.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Twenty-five patients (19 men and 6 women; mean age, 68 ± 7 years [± SD]) participated in the study. All patients had COPD according to the criteria of the American Thoracic Society and had PaO2 levels > 60 mm Hg measured at rest.12 The subject group was compared to a control group consisting of 26, age-matched, healthy, nonsmoking subjects with a mean age of 56 ± 8 years.

All patients were investigated during a stable period of their disease. Patients with a history of systemic hypertension, ischemic or valvular heart disease, or episodes of right-sided and/or left-sided cardiac failure were excluded from the study. The protocol was approved by the Medical Ethical Committee of the Vrije Universiteit Medical Center. All patients were informed about the aim of the study and gave their informed consent.

Lung Function
Lung function measurements were performed within 2 months of MRI measurements. Dynamic and static lung volumes and single-breath diffusion capacity of the lung for carbon monoxide (DLCO) [max 229 and 6200; SensorMedics; Yorba Linda, CA] were determined according to the European Respiratory Society guidelines and compared to the European Respiratory Society reference values.13 Arterial blood gases were measured at rest with the patient breathing room air.

MRI Protocol
The patients and control subjects were scanned using a 1.5 T Siemens Vision whole-body system and a phased-array body coil (Siemens Medical Systems; Erlangen, Germany). All image acquisition was ECG R-wave gated. During all image acquisitions (including the scout imaging for localization of the heart), the subjects were instructed to hold their breath after moderate inspiration. The average time required for the protocol was approximately 30 min.

Short-Axis Ventricular Imaging
The horizontal long-axis view was determined in a late-diastolic frame.14 By using the end-diastolic cine frame of this long-axis view, a series of parallel short-axis image planes was defined starting at the base of the LV and RV, and encompassing the entire LV and RV from base to apex. The most basal image plane was positioned close to the transition of the myocardium to the mitral and tricuspid valve leaflets (at a distance of half the slice thickness). This ensured that the most basal part of the LV and RV were also evaluated. At every short-axis plane, a breath-hold cine acquisition was performed. For the cine imaging, a gradient-echo pulse sequence was applied with segmented k space, 7 phase-encoding lines per heartbeat, and a temporal resolution of 80 ms. Echo sharing yielded a temporal frame at every 40 ms. The excitation angle was 25°, the field of view was 280 x 320 mm, and matrix size was 126 x 256. Slice thickness was 6 mm and gap was 4 mm, resulting in a slice distance of 10 mm. Heart rate was monitored during the acquisition of the short-axis images.

Image Analysis
The images were processed on a Sun Sparc station (Sun Microsystems; Mountain View, CA) using the "MASS" software package (Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands). All MRI data were processed by a blinded observer. End-diastole was defined as the first temporal frame directly after the R-wave of the ECG. End-systole was defined as the temporal frame at which the image showed the smallest RV and LV cavity area, usually 240 to 320 ms after the R-wave. Epicardial and endocardial contours were manually traced. The papillary muscles were excluded from the RV and LV volume and included in the determination of RV and LV mass. Because of RV and LV shortening, at least one extra slice at the RV and LV base was needed at end-diastole to encompass the complete RV and LV. If the most basal image at end-systole was difficult to interpret (due to partial volume effects), this most basal plane was projected on to the end-systole frame of the long-axis cine images. The resulting projection line on this long-axis view was used to decide whether or not to include the end-systolic short axis image as a part of the LV or RV. The LV end-diastolic mass was obtained from the volume of the LV muscle tissue including the interventricular septum. The RV end-diastolic mass was obtained in a similar way, but excluding the septum. In the mass calculation, the specific weight of muscle tissue was 1.05 g/cm3 based on an earlier study in dogs.15 The distensibility of the right pulmonary artery defined as maximal systolic cross-sectional area minus end-diastolic cross-sectional area divided by the end-diastolic cross-sectional area was derived form cine images acquired in a plane orthogonal to the right pulmonary artery.8 The distensibility of the right pulmonary artery was regarded as an indicator of pulmonary artery pressure (PAP).1617

Statistical Analysis
The results were reported as mean ± SD. Differences between patients and control subjects were tested using the Student t test for two independent groups. For analysis of factors associated with RV hypertrophy, univariate regression analysis was performed. Data were analyzed using software (SigmaStat 2.03; SPSS; Chicago, IL); p < 0.05 was considered significant.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Mean pulmonary function data and the arterial blood gas results of the 25 COPD patients are presented in Table 1 . Most of the patients had considerable bronchial obstruction, as reflected by a mean FEV1 of 1.23 L and a mean FEV1/vital capacity (VC) ratio of 34%. None of the patients had an increased PaCO2 level. Nineteen patients had PaO2 > 80 mm Hg, and only three patients had PaO2 levels between 60 mm Hg and 70 mm Hg.


View this table:
[in this window]
[in a new window]

  		Table 1. Pulmonary Function and Arterial Blood Gas Data of the COPD Patients

 
Figure 1 shows the short- and long-axis of the heart of a COPD patient and a healthy control subject during end-diastole. The short-axis image corresponds to the short-axis view of the heart at the mid-level between base and apex. As compared to the healthy subjects, the position of the heart of the COPD patient is rotated and shifted to a more vertical position in the thoracic cavity due to hyperinflation of the lungs, increasing the retrosternal space. The short- and long-axis images showed RV hypertrophy and an altered morphology of the RV and LV.



View larger version (142K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Short- and long-axis MRIs of the heart in a healthy subject and a COPD patient.

 
Table 2 compares the cardiac parameters between subjects and control groups. Stroke volume was significantly lower in the COPD group. Since the heart rate in the COPD group was higher than the control subjects, cardiac output was similar between both groups. RV wall mass was significantly higher in the patient group, whereas LV wall mass did not differ significantly between both groups. Both RV end-diastolic volume and end-systolic volume were significantly lower compared to the control subjects. While LV end-diastolic volume was lower compared to the control subjects, LV end-systolic volume was within a normal range. RV and LV ejection fractions were similar in the COPD group compared to the control group. RV systolic dysfunction, defined as RV ejection fraction < 45%, was present in 20% of the patients, and LV systolic dysfunction, defined according to the same criteria, was present in 16% of the patients. None of the healthy subjects had a RV or LV ejection fraction < 45%.


View this table:
[in this window]
[in a new window]

  		Table 2. Structural and Functional Cardiac Parameters*

 
The right pulmonary artery distensibility was not significantly different in the patient group (37 ± 18%) compared to the control subjects (39 ± 17%). This suggests that pulmonary hypertension was not present in the COPD patients during resting conditions.

Table 3 presents the results of the univariate regression analysis comparing RV mass and the pulmonary function parameters in the patient group. No significant relationship was found.


View this table:
[in this window]
[in a new window]

  		Table 3. Univariate Regression Analysis Between RV Mass and Pulmonary Function Parameters of the Patient Group

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study is the first documentation of RV hypertrophy as an early sign of adaptation of the RV to pressure overload in COPD. It shows that even in patients with normoxia (PaO2 > 80 mm Hg) or mild hypoxemia (PaO2 > 60 mm Hg), this adaptation is present. No data relative to sleep-related hypoxemia were obtained from these patients. Since the patients had no history of systemic hypertension, or ischemic or valvular heart disease, the changes in structure and function of the RV and LV were considered to be adaptive responses to COPD. The cardiac parameters of the control group were within the same range as two earlier MRI studies1415 providing reference data for the RV and LV.

Although we did not measure PAP in our patients, it can be safely assumed that pulmonary hypertension was not present during resting conditions because of the following: (1) all our patients had PaO2 > 60 mm Hg, and Oswald-Mammoser et al2 showed that pulmonary hypertension is rarely present at rest in COPD patients with PaO2 > 60 mm Hg; and (2) the distensibility of the right pulmonary artery, an indirect measure of PAP, did not show a significant difference between the COPD patients and control subjects. The altered structure of the RV can thus be attributed to the intermittent increases in PAP that most likely occur during exercise and sleep in COPD.1218

Our results showed that marked RV hypertrophy accompanies decreased RV end-diastolic volume. The hypertrophy is classified as concentric hypertrophy and is consistent with the well-known radiologic characteristics of emphysema patients with a narrow vertical heart. RV systolic function was similar in COPD and control groups. This finding is in agreement with those of earlier studies192021 that show well-preserved RV systolic function in most patients with COPD. Thus, although our patients exhibited concentric hypertrophy as an early sign of intermittent pressure overload, this hypertrophy was not accompanied by a loss of systolic function. This finding is in agreement with earlier studies22 on cardiac hypertrophy that showed that concentric hypertrophy occurs in case of intermittent pressure overload. A pressure overload causes an increase in RV wall stress. By thickening the wall, the ventricle tends to normalize wall stress. This adaptation to intermittent pressure-overload does not depress systolic function. In the above-mentioned studies,192021 it has also been shown that dilatation of the ventricle occurs when the hypertrophy is not able to keep pace with increased systolic pressure and/or volume overload. This latter mechanism might explain the findings of a previous echocardiographic study by Boussuges et al,6 who demonstrated an increase of RV diameters in patients with severe COPD with pronounced hypoxemia (mean PaO2, 54 mm Hg). Thus, it can be postulated that in patients with COPD concentric RV hypertrophy precedes dilating RV hypertrophy. We did not find a significant relation between RV mass and pulmonary function parameters. This may be explained by the small range of pulmonary function parameters in our patients due to our selection criteria. Thus, although our data did not show a relationship between the pulmonary function parameters and RV mass, it does not exclude such a relationship in a more heterogeneous patient group.

LV mass was not increased in our COPD group. In contrast, an earlier postmortem study4 showed that the LV wall is thickened in patients with chronic cor pulmonale without a history of hypertension who died of respiratory failure due to end-stage chronic pulmonary disease. These findings indicate that LV hypertrophy occurs in patients with severe COPD but is absent in patients with moderate COPD without clinical signs of cor pulmonale. Animal studies2324 have shown that the magnitude of LV hypertrophy is well correlated with the duration of RV pressure overload.

Structural changes of the RV might also alter LV structure and filling due to the phenomenon of ventricular interdependency. This might explain lowered LV end-diastolic volumes found in COPD patients.62526 LV ejection fraction, as a global measure of LV systolic function, was relatively normal in the patient group. Only 16% of the patients had LV systolic dysfunction, corresponding to findings in earlier studies.27

In conclusion, the data obtained in this study indicate that concentric RV hypertrophy is already present in COPD patients with normoxemia or mild hypoxemia, probably due to intermittent increases in PAPs that occur during exercise and/or sleep. Concentric RV hypertrophy does not impair RV and LV systolic function.


   Footnotes
 
Abbreviations: DLCO = diffusion capacity of the lung for carbon monoxide; LV = left ventricle/ventricular; PAP = pulmonary artery pressure; RV = right ventricle/ventricular; VC = vital capacity

Received for publication March 31, 2004. Accepted for publication December 3, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Burrows, B, Kettel, LJ, Niden, AH, et al (1972) Patterns of cardiovascular dysfunction in chronic obstructive lung disease. N Engl J Med 286,912-918[ISI][Medline]
  2. Oswald-Mammosser, M, Apprill, M, Bachez, P, et al Pulmonary hemodynamics in chronic obstructive pulmonary disease of the emphysematous type. Respiration 1991;58,304-310[ISI][Medline]
  3. Incalzi, RA, Fuso, L, De Rosa, M, et al Electrocardiographic signs of chronic cor pulmonale: a negative prognostic finding in chronic obstructive pulmonary disease. Circulation 1999;99,1600-1605[Abstract/Free Full Text]
  4. Calverley, PMA, Howatson, R, Flenley, DC, et al Clinicopathological correlations in cor pulmonale. Thorax 1992;47,494-498[Abstract]
  5. Scharf, SM, Iqbal, M, Keller, C, et al Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med 2002;166,314-322[Abstract/Free Full Text]
  6. Boussuges, A, Pinet, C, Molenat, F, et al Left atrial and ventricular filling in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162,670-675[Abstract/Free Full Text]
  7. Longmore, DB, Klipstein, RH, Underwood, SR, et al Dimensional accuracy of magnetic resonance studies of the heart. Lancet 1985;1,1360-1362[ISI][Medline]
  8. Marcus, JT, Vonk Noordegraaf, A, De Vries, PMJM, et al MRI evaluation of right ventricular pressure overload in chronic obstructive pulmonary disease. J Magn Reson Imaging 1998;8,999-1005[ISI][Medline]
  9. Turnbull, LW, Ridgway, JP, Biernacki, W, et al Assessment of the right ventricle by magnetic resonance imaging in chronic obstructive lung disease. Thorax 1990;45,597-601[Abstract]
  10. Pattynama, PM, Willems, LN, Smit, AH, et al Early diagnosis of cor pulmonale with MR imaging of the right ventricle. Radiology 1992;182,375-379[Abstract/Free Full Text]
  11. Saito, H, Dambara, T, Aiba, M, et al Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging. Am Rev Respir Dis 1992;146,1576-1581[ISI][Medline]
  12. American Thoracic Society.. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152,S77-S120[Medline]
  13. Quanjer, PH, Tammeling, GJ, Cotes, JE, et al Lung volumes and forced ventilatory flows: report working party standardization of lung function tests. European Community for Steel and Coal. Eur Respir J 1993;6(suppl),5-40
  14. Marcus, JT, De Waal, LK, Gotte, MJW, et al MRI derived left ventricular function parameters and mass in healthy young adults: relation with gender and body size. Int J Cardiac Imaging 1999;15,411-419[CrossRef][ISI][Medline]
  15. Lorenz, CH, Walker, ES, Morgan, VL, et al Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging. J Cardiovasc Magn Res 1999;1,7-21[ISI][Medline]
  16. Bogren, HG, Klipstein, RH, Mohiaddin, RH, et al Pulmonary artery distensibility and blood flow patterns: a magnetic resonance study of normal subjects and of patients with pulmonary arterial hypertension. Am Heart J 1989;118,234-247[CrossRef][ISI][Medline]
  17. Reuben, SR Compliance of the human pulmonary arterial system in disease. Circ Res 1971;29,40-50[Abstract/Free Full Text]
  18. Raeside, DA, Brown, A, Patel, KR, et al Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD. Thorax 2002;57,1050-1053[Abstract/Free Full Text]
  19. Biernacki, Q, Flenley, DC, Muir, AL, et al Pulmonary hypertension and right ventricular function in patients with COPD. Chest 1988;94,169-175
  20. France, AJ, Prescott, RJ, Biernacki, W, et al Does right ventricular function predict survival in patients with chronic obstructive lung disease? Thorax 1988;43,621-626[Abstract]
  21. Oliver, RM, Fleming, JS, Waller, DDG Right ventricular function at rest and during exercise in chronic obstructive pulmonary disease: comparison of two radionuclide techniques. Chest 1993;102,74-80
  22. Grossman, W Cardiac hypertrophy: useful adaptation or pathologic process? Am J Med 1980;69,576-584[CrossRef][ISI][Medline]
  23. Gomez, A, Unruh, H, Mink, SN Altered left ventricular chamber stiffness and isovolumetric relaxation in dogs with chronic pulmonary hypertension caused by emphysema. Circulation 1993;87,247-260[Abstract/Free Full Text]
  24. Laks, MM, Morady, F, Garner, D, et al Relaxation of ventricular volume, compliance, and mass in the normal and pulmonary arterial banded canine heart. Cardiovascular Res 1972;6,187-198[ISI][Medline]
  25. Kohama, A, Tanouchi, J, Masatsugu, H, et al Pathologic involvement of the left ventricle in chronic obstructive pulmonary disease. Chest 1990;98,794-800[Abstract/Free Full Text]
  26. Vonk Noordegraaf, A, Marcus, JT, Roseboom, B, et al The effect of right ventricular hypertrophy on left ventricular ejection fraction in pulmonary emphysema. Chest 1997;112,640-645[Abstract/Free Full Text]
  27. Vizza, D, Lynch, JP, Ochoa, LL, et al Right and left ventricular dysfunction in patients with severe pulmonary disease. Chest 1998;113,576-583[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 ChestHome page
A. M. Taveira-DaSilva, O. M. Hathaway, V. Sachdev, Y. Shizukuda, C. W. Birdsall, and J. Moss
Pulmonary Artery Pressure in Lymphangioleiomyomatosis: An Echocardiographic Study
Chest, November 1, 2007; 132(5): 1573 - 1578.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. J. Faber, M. Dalinghaus, I. M. Lankhuizen, P. Steendijk, W. C. Hop, R. G. Schoemaker, D. J. Duncker, J. M. J. Lamers, and W. A. Helbing
Right and left ventricular function after chronic pulmonary artery banding in rats assessed with biventricular pressure-volume loops
Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1580 - H1586.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vonk-Noordegraaf, A.
Right arrow Articles by Postmus, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vonk-Noordegraaf, A.
Right arrow Articles by Postmus, P. E.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS