- Email: [email protected]
Scaling considerations in the cardiovascular pathophysiology of obese patients
International Journal of Cardiology 191 (2015) 312–313
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Scaling considerations in the cardiovascular pathophysiology of obese patients S.S. Hothi a,b,⁎, D.K.H. Tan c, G. Partridge d, L.B. Tan d a
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK Physiological Laboratory and Department of Biochemistry, University of Cambridge, Cambridge, UK Newcastle Medical School, Newcastle, UK d Leeds General Infirmary, Leeds, UK b c
a r t i c l e
i n f o
Article history: Received 6 May 2015 Accepted 7 May 2015 Available online 9 May 2015 Keywords: Heart failure Cardiac function Obesity Cardiopulmonary exercise testing Oxygen consumption Scaling
To the Editor, We would like to thank Krachler et al. [1] for their letter regarding our study “Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction?” [2]. Krachler's group have concluded from their own data that correcting VO2max with total body mass (BM) “systematically underestimates cardiorespiratory fitness in obese individuals”. This conclusion is indeed consistent with our data as shown in Figs. 2 and 3 of our paper. Both Krachler's and our groups have arrived at the same conclusion that VO2max/kg corrected with total BM is untenable, and we accordingly call for the physiology and cardiology communities to discontinue this scientifically unsound practice. In particular, basing life-and-death decision-making (e.g., for cardiac transplantation or ventricular assist device implantation [3]) on VO2max/kg would require urgent updating. The next issue that Krachler brought up was that of making “scaling for body composition” a requirement. Our hearts would like to see this implemented as soon as possible, but our minds recognise a few lingering questions. First, we are aware that due to limited resources in health
⁎ Corresponding author at: Physiological Laboratory and Department of Biochemistry, University of Cambridge, UK. E-mail address: [email protected] (S.S. Hothi).
http://dx.doi.org/10.1016/j.ijcard.2015.05.047 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
service, the extra cost of reliably measuring body composition using dual energy X-ray absorptiometry or magnetic resonance imaging may not be widely available. Bioimpedance methods may be acceptable to some, but we are as yet unconvinced by its general reliability. Moreover, body composition is usually compartmentalised into lean mass and fat mass. It is true that during exercise fatty tissues are not as actively metabolising, but the fat-free component is heterogeneous, containing bones and other organs (e.g., GI tract, liver, spleen, kidneys) to which perfusion reduces during exercise and which are rather inactively metabolising compared to highly metabolically active muscles. Therefore, scaling by lean body mass (LBM) defined as total body mass minus fat mass is an improvement over scaling by total body mass, but is as yet an incomplete solution due to the heterogeneity of the LBM compartments defined in this way. Scaling in the animal kingdom is essential because the differences in size are even more prominent. While the body weight of a small human female adult versus the largest man may differ by a hundred fold, the difference in size between a blue whale and a hamster is a million fold. Thus in the comparative study of animal physiology, Schmidt-Nielsen has defined that “scaling deals with the structural and functional consequences of changes in size or scale among otherwise similar organisms” [4]. In cardiology, mathematical methods to adjust for body sizes and composition have been proposed [5,6], but there are still on-going debates about the best ways to find the most reliable correction factors. When considering scaling in cardiology, there is now an urgent need to reappraise all correction factors commonly used in practice which were based on rather weak ancient assumptions and may not be appropriate nowadays. Related to VO2max is cardiac output (CO) which in cardiological practice is traditionally corrected with body surface area (BSA) to give cardiac index (CI). While the physical basis of using BSA to correct size differences in rates of body heat transfer is clear and logical [7], the tradition of correcting cardiac volumes and flows (CO and echocardiographic LV mass, volume or dimensions) with BSA does not appear to have similar and sound physical bases. While BM is easily measured, BSA is not directly measured but usually estimated using various equations, not all of which are reliable [8]. CO is, however, a factor in the equation for O2 uptake, VO2 = CO × ΔO2 (a–v). Correcting the left side of the equation with BM and the other side with BSA illustrates an absurd state of affair in current cardiological practice. Correcting for body size and composition is truly an outstanding urgent problem in cardiology. There are therefore many difficult issues that need to be
S.S. Hothi et al. / International Journal of Cardiology 191 (2015) 312–313
resolved before scaling can become routinely and unequivocally applied into cardiological practice. Is there any alternative? Pending resolution of the scaling issues in cardiology, an alternative approach, is to compare the measurements with representative normal healthy controls as shown in our paper [2]. For peak cardiac power values, such reference data were obtained from our previous study [9]. This is also in line with routine clinical practice in other medical specialties where measured variables (e.g., haemoglobin and serum electrolytes) are interpreted with reference to values obtained from normals. We can express peak cardiac power as a percentage of the average values from age- and sex-matched controls [10]. Similar approaches for VO2max have been covered in a recent review [11]. If the controls happen to have similar lean body masses as the patient cohort, the scaling corrections would then apply equally to both groups thereby leaving the relative percentage values invariant. Finally, we are also delighted that Krachler's group has also astutely recognised that the stronger hearts of obese HF patients can partly account for the puzzling reverse epidemiology of obesity in HF patients. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] B. Krachler, K. Savonen, P. Komulainen, M. Hassinen, T.A. Lakka, R. Rauramaa, VO2max/kg is expected to be lower in obese individuals! Int. J. Cardiol. 189 (2015) 234.
313
[2] S.S. Hothi, D.K. Tan, G. Partridge, L.B. Tan, Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction? Int. J. Cardiol. 184 (2015) 755–762. [3] M.R. Mehra, J. Kobashigawa, R. Starling, S. Russell, P.A. Uber, J. Parameshwar, P. Mohacsi, S. Augustine, K. Aaronson, M. Barr, Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006, J. Heart Lung Transplant. 25 (9) (2006) 1024–1042. [4] K. Schmidt-Nielsen, Why Is Animal Size so Important? Cambridge University Press, London, 1984. 1–241. [5] F.E. Dewey, D. Rosenthal, D.J. Murphy Jr., V.F. Froelicher, E.A. Ashley, Does size matter? Clinical applications of scaling cardiac size and function for body size, Circulation 117 (17) (2008) 2279–2287. [6] A.M. Nevill, S. Bate, R.L. Holder, Modeling physiological and anthropometric variables known to vary with body size and other confounding variables, Am. J. Phys. Anthropol. (Suppl. 41) (2005) 141–153. [7] P. Szmuk, M.F. Rabb, J.E. Baumgartner, J.M. Berry, A.M. Sessler, D.I. Sessler, Body morphology and the speed of cutaneous rewarming, Anesthesiology 95 (1) (2001) 18–21. [8] G. Turcotte, Erroneous nomograms for body-surface area, N. Engl. J. Med. 300 (1979) 300–1339. [9] D.F. Goldspink, K.P. George, P.D. Chantler, R.E. Clements, L. Sharp, G. Hodges, C. Stephenson, T.P. Reilly, A. Patwala, T. Szakmany, L.B. Tan, N.T. Cable, A study of presbycardia, with gender differences favoring ageing women, Int. J. Cardiol. 137 (3) (2009) 236–245. [10] D.K. Tan, S.S. Hothi, W. Macdonald, D. Schlosshan, L.B. Tan, Impacts of valve intervention on the Functional REServe of the Heart: the FRESH-valve pilot study, Int. J. Cardiol. 187 (2015) 491–501. [11] P. Gargiulo, S. Olla, C. Boiti, M. Contini, P. Perrone-Filardi, P. Agostoni, Predicted values of exercise capacity in heart failure: where we are, where to go, Heart Fail. Rev. 19 (5) (2014) 645–653.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Scaling considerations in the cardiovascular pathophysiology of obese patients S.S. Hothi a,b,⁎, D.K.H. Tan c, G. Partridge d, L.B. Tan d a
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK Physiological Laboratory and Department of Biochemistry, University of Cambridge, Cambridge, UK Newcastle Medical School, Newcastle, UK d Leeds General Infirmary, Leeds, UK b c
a r t i c l e
i n f o
Article history: Received 6 May 2015 Accepted 7 May 2015 Available online 9 May 2015 Keywords: Heart failure Cardiac function Obesity Cardiopulmonary exercise testing Oxygen consumption Scaling
To the Editor, We would like to thank Krachler et al. [1] for their letter regarding our study “Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction?” [2]. Krachler's group have concluded from their own data that correcting VO2max with total body mass (BM) “systematically underestimates cardiorespiratory fitness in obese individuals”. This conclusion is indeed consistent with our data as shown in Figs. 2 and 3 of our paper. Both Krachler's and our groups have arrived at the same conclusion that VO2max/kg corrected with total BM is untenable, and we accordingly call for the physiology and cardiology communities to discontinue this scientifically unsound practice. In particular, basing life-and-death decision-making (e.g., for cardiac transplantation or ventricular assist device implantation [3]) on VO2max/kg would require urgent updating. The next issue that Krachler brought up was that of making “scaling for body composition” a requirement. Our hearts would like to see this implemented as soon as possible, but our minds recognise a few lingering questions. First, we are aware that due to limited resources in health
⁎ Corresponding author at: Physiological Laboratory and Department of Biochemistry, University of Cambridge, UK. E-mail address: [email protected] (S.S. Hothi).
http://dx.doi.org/10.1016/j.ijcard.2015.05.047 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
service, the extra cost of reliably measuring body composition using dual energy X-ray absorptiometry or magnetic resonance imaging may not be widely available. Bioimpedance methods may be acceptable to some, but we are as yet unconvinced by its general reliability. Moreover, body composition is usually compartmentalised into lean mass and fat mass. It is true that during exercise fatty tissues are not as actively metabolising, but the fat-free component is heterogeneous, containing bones and other organs (e.g., GI tract, liver, spleen, kidneys) to which perfusion reduces during exercise and which are rather inactively metabolising compared to highly metabolically active muscles. Therefore, scaling by lean body mass (LBM) defined as total body mass minus fat mass is an improvement over scaling by total body mass, but is as yet an incomplete solution due to the heterogeneity of the LBM compartments defined in this way. Scaling in the animal kingdom is essential because the differences in size are even more prominent. While the body weight of a small human female adult versus the largest man may differ by a hundred fold, the difference in size between a blue whale and a hamster is a million fold. Thus in the comparative study of animal physiology, Schmidt-Nielsen has defined that “scaling deals with the structural and functional consequences of changes in size or scale among otherwise similar organisms” [4]. In cardiology, mathematical methods to adjust for body sizes and composition have been proposed [5,6], but there are still on-going debates about the best ways to find the most reliable correction factors. When considering scaling in cardiology, there is now an urgent need to reappraise all correction factors commonly used in practice which were based on rather weak ancient assumptions and may not be appropriate nowadays. Related to VO2max is cardiac output (CO) which in cardiological practice is traditionally corrected with body surface area (BSA) to give cardiac index (CI). While the physical basis of using BSA to correct size differences in rates of body heat transfer is clear and logical [7], the tradition of correcting cardiac volumes and flows (CO and echocardiographic LV mass, volume or dimensions) with BSA does not appear to have similar and sound physical bases. While BM is easily measured, BSA is not directly measured but usually estimated using various equations, not all of which are reliable [8]. CO is, however, a factor in the equation for O2 uptake, VO2 = CO × ΔO2 (a–v). Correcting the left side of the equation with BM and the other side with BSA illustrates an absurd state of affair in current cardiological practice. Correcting for body size and composition is truly an outstanding urgent problem in cardiology. There are therefore many difficult issues that need to be
S.S. Hothi et al. / International Journal of Cardiology 191 (2015) 312–313
resolved before scaling can become routinely and unequivocally applied into cardiological practice. Is there any alternative? Pending resolution of the scaling issues in cardiology, an alternative approach, is to compare the measurements with representative normal healthy controls as shown in our paper [2]. For peak cardiac power values, such reference data were obtained from our previous study [9]. This is also in line with routine clinical practice in other medical specialties where measured variables (e.g., haemoglobin and serum electrolytes) are interpreted with reference to values obtained from normals. We can express peak cardiac power as a percentage of the average values from age- and sex-matched controls [10]. Similar approaches for VO2max have been covered in a recent review [11]. If the controls happen to have similar lean body masses as the patient cohort, the scaling corrections would then apply equally to both groups thereby leaving the relative percentage values invariant. Finally, we are also delighted that Krachler's group has also astutely recognised that the stronger hearts of obese HF patients can partly account for the puzzling reverse epidemiology of obesity in HF patients. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] B. Krachler, K. Savonen, P. Komulainen, M. Hassinen, T.A. Lakka, R. Rauramaa, VO2max/kg is expected to be lower in obese individuals! Int. J. Cardiol. 189 (2015) 234.
313
[2] S.S. Hothi, D.K. Tan, G. Partridge, L.B. Tan, Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction? Int. J. Cardiol. 184 (2015) 755–762. [3] M.R. Mehra, J. Kobashigawa, R. Starling, S. Russell, P.A. Uber, J. Parameshwar, P. Mohacsi, S. Augustine, K. Aaronson, M. Barr, Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006, J. Heart Lung Transplant. 25 (9) (2006) 1024–1042. [4] K. Schmidt-Nielsen, Why Is Animal Size so Important? Cambridge University Press, London, 1984. 1–241. [5] F.E. Dewey, D. Rosenthal, D.J. Murphy Jr., V.F. Froelicher, E.A. Ashley, Does size matter? Clinical applications of scaling cardiac size and function for body size, Circulation 117 (17) (2008) 2279–2287. [6] A.M. Nevill, S. Bate, R.L. Holder, Modeling physiological and anthropometric variables known to vary with body size and other confounding variables, Am. J. Phys. Anthropol. (Suppl. 41) (2005) 141–153. [7] P. Szmuk, M.F. Rabb, J.E. Baumgartner, J.M. Berry, A.M. Sessler, D.I. Sessler, Body morphology and the speed of cutaneous rewarming, Anesthesiology 95 (1) (2001) 18–21. [8] G. Turcotte, Erroneous nomograms for body-surface area, N. Engl. J. Med. 300 (1979) 300–1339. [9] D.F. Goldspink, K.P. George, P.D. Chantler, R.E. Clements, L. Sharp, G. Hodges, C. Stephenson, T.P. Reilly, A. Patwala, T. Szakmany, L.B. Tan, N.T. Cable, A study of presbycardia, with gender differences favoring ageing women, Int. J. Cardiol. 137 (3) (2009) 236–245. [10] D.K. Tan, S.S. Hothi, W. Macdonald, D. Schlosshan, L.B. Tan, Impacts of valve intervention on the Functional REServe of the Heart: the FRESH-valve pilot study, Int. J. Cardiol. 187 (2015) 491–501. [11] P. Gargiulo, S. Olla, C. Boiti, M. Contini, P. Perrone-Filardi, P. Agostoni, Predicted values of exercise capacity in heart failure: where we are, where to go, Heart Fail. Rev. 19 (5) (2014) 645–653.