Editorial Manager(tm) for The Journal of Thoracic and Cardiovascular Surgery Manuscript Draft

Manuscript Number:

Title: Congestive failure: treat the disease not the symptom - return to normalcy / Part II -- the experimental approach

Article Type: Editorial, invited

Section/Category: ACD: Acquired Cardiovascular Disease

Corresponding Author: Dr. Gerald D. Buckberg, M.D.

Corresponding Author's Institution: UCLA Medical Center

First Author: Gerald D. Buckberg, M.D.

Order of Authors: Gerald D. Buckberg, M.D. Manuscript (invited)

1 2 3 4 TITLE: 5 6 Congestive : treat the disease not the symptom - return to 7 normalcy / Part II -- the experimental approach 8 9 10 AUTHOR: Gerald D. Buckberg, M.D. 11 12 13 14 ADDRESS FOR CORRESPONDENCE: 15 David Geffen School of Medicine at UCLA, Dept. of Surgery 16 10833 Le Conte Avenue, 62-258 CHS 17 18 Los Angeles, CA 90095 19 Email : [email protected] 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 1 64 65 1 2 3 4 The report in this volume by Zhang and associates (1) applies an important 3- 5 6 dimensional MRI tagging method to demonstrate that altering ventricular geometry by 7 employing Dor procedure (as they interpreted this operation) in sheep in congestive heart 8 failure increases systolic circumferential shortening in remote muscle. These 9 experimental changes document the clinical improvement in remote muscle function 10 reported world wide with LV restoration (2;3). Such application of advanced imaging 11 12 methods allows studies to focus upon how interventions improve function by changing 13 ventricular muscle deformation, that occurs sequentially during the cardiac twisting 14 motion. Furthermore, this regional functional data allows differentiation from non 15 functional remote regions that shows are displaced without contracting, 16 together with providing a time course for displaying how global function is affected by 17 18 cardiac rebuilding. 19 20 Normal and Abnormal Form 21 22 23 The surgical approach to congestive heart failure, like other operative objectives 24 should treat the disease, not the symptom, and return structures toward normal 25 as described by others (4) and became the title of my 2001 JCTVS Editorial (5). 26 The geometric disease in ischemic dilated cardiomyopathy is the spherical 27 chamber, which is different than the elliptical of conical normal heart shape 28 29 (Figure 1). The symptom is the spherical chamber, whereby normal helical 30 chamber develops a more circular configuration that may flatten fiber 31 orientration and alter performance (6) (7). 32 33 34 35 36 Despite imaging advantages, the experimental design of this study has a major 37 flaw, since baseline is ascribed to the infarction state, rather than to the normal 38 heart. The authors held fast to repeated requests to supplement their data base 39 40 with a design that introduces normality as a reconstructive guideline for operative 41 interventions. It seems that, aside from supplying superb imaging technology, the 42 surgical planning strategy must also recognize and codify normality (which exists 43 before the infarction), show how disease distorts this (their preoperative control), 44 45 identify how and why the intervention selected rebuilds normality, and relate 46 results toward the limitations of the selected procedure. For example, if normality 47 was not recaptured, the discussion should identify if this is a problem with the 48 operation method, or related to timing of postoperative measurements. 49 50 51 52 53 54 55 56 Border and Remote Muscle 57 58 Prior studies addressed the peri infarction border zone showing that the issue 59 was impaired contractile function, rather than increased wall stress (8), and 60 61 62 63 2 64 65 1 2 3 4 directed less attention toward the remote muscle that rapidly impairs function 5 6 after anterior wall infarction in relation to ventricular shape (9). The tagging 7 study in 2000 by Bogeart introduced the key link whereby border and remote 8 muscle zones become combined culprits for dysfunction after ventricular volume 9 is increased by anterior infarction (9). Zhang’s study coalesces these data and is 10 helpful in directing attention of cardiologists and surgeons toward malfunction of 11 12 global muscle, whose recovery is quantified by returning deformation of the less 13 efficient stretched muscle towards normal following ventricular restoration. 14 15 Kramer in 2002 (10) followed Boegart’s approach and employed tagging 16 17 methods to quantify remote muscle circumferential shortening improvement 18 following restoration, compared the changes to control studies, showed this 19 spatial configuration change (Figure 2a), and adhered to the aforementioned 20 surgical study planning concept. Similar findings of remote muscle 21 circumferential deformation improvement were recently reported by White’s team 22 23 at the Cleveland Clinic (11). Editorial suggestions to include this information were 24 not followed, so that a restricted background analysis underlies the manuscript’s 25 introduction statements about prior study limitations. Furthermore, non MRI 26 studies by Taniguchi, codified improved velocity of remote muscle circumferential 27 fiber shortening (12), showed regional stress, function, and remodeling improves 28 29 after aneurysmectomy, and also demonstrated these results were not achieved 30 by CABG alone, thereby answering the introduction’s supposition that 31 confounding effects of other procedures had not yet been addressed. 32 33 34 Dilemma of abnormal shape 35 36 Failure to achieve normal shape is the infrastructure of the limitations of a host of 37 non reconstructive CHF therapies such as CABG, rebuilding in 38 ischemic cardiomyopathy, biventricular pacing, defibrillator devices and a 39 40 spectrum of pharmacologic treatments that alter neuro endocrine factors, yet 41 exclude addressing the scar nidus that underlies subsequent remote ventricular 42 stretch. The sphere was retained in this study (Figure 2b), although slightly less 43 circular. It seems the surgical objective should be to restore normality, rather 44 45 than making the heart “less sick”. 46 47 48 49 Certainly, the investigator is free to design each study and set goals that relate to 50 51 how rebuilding improves function via the Starling relationship. However, the 52 analysis should also echo the relationship of these objectives toward a) how their 53 “Dor procedure” reproduces what was initially described, and b) define 54 mechanisms that allow observed function to improve. Their goal of 50% surgical 55 neck reduction to increase regional strain was achieved, but differs from Dor’s 56 57 objectives (to whom this operation is ascribed) that indicate “the endoventricular 58 suture helps restore the curvature towards its shape before infarction, and helps 59 in selection of the size, shape and orientation of the patch” (2). 60 61 62 63 3 64 65 1 2 3 4 5 6 These limitations are evident when current results in Fig 2b are compared to 7 clinical findings of Kramer in Figure 2a, who also included preoperative normal 8 configurations for comparison. While the circular configurations are evident 9 during infarction, a similar, but slightly less spherical shape followed this 10 experiment, whereas the normal conical shape was achieved after clinical LV 11 12 reconstruction. Editorial suggestions to include an image of the control natural 13 ventricular shape were declined; inclusion of such a normal elliptical shape 14 would a) allow contrast with the circular or spherical chamber that develops after 15 infarction, b) demonstrate the spherical configuration is relatively retained after 16 experimental patch placement, c) potentially permit the authors and readers to 17 18 question about the role of geometry in determining function and d) possibly 19 generate questions about what function could be expected if the rebuilding 20 procedure reconstructed the normal elliptical form rather than a smaller sphere. 21 22 23 Importance of Normal Shape 24 25 Unfortunately, the manuscript’s statement that no one knows about optimal post 26 operative shape skirts away from the beauty of understanding and driving toward 27 rebuilding the normal shape. Advantages of this configuration are evident from 28 29 tagging MRI studies of Bogeart (13) demonstrating regional non uniformity of 30 the normal left , whereby deformation accentuates as sequential normal 31 heart motion progresses from base to apex. Consequently, the stated “idealized 32 LV wall geometry as a hemispherical shell” does not exist in the conical heart, 33 34 and their relatively spherical shaped end point following LV rebuilding (Figure 35 1b) is clinically described as a less ideal spherical box-like chamber (14) . 36 37 Reconstruction of a more normal elliptical shape aims toward Dor’s objective of 38 returning configuration towards its shape before infarction, and underlies 39 40 development of clinically employed shaping devices and conically shaped 41 mandrels. (15) This normal form related endpoint has led to placing the oblique 42 patch above the scar to reconstruct normal shape (16) as well as repeating this 43 intervention in ischemic non scarred septum muscle in dilated failing in 44 45 Russia (17) with similarly improved late results to those after scar exclusion, and 46 underlies a recently posed question “is the goal to exclude the disease or to 47 rebuild form ?”(18) Decisions toward this goal (Figure 3) evolved from 48 recognizing higher late mortality in Dor’s long term experience (19) after a larger 49 chamber was retained when excluding the scar was the anatomic reconstruction 50 51 end point. This selection criteria led to postoperative retention of more dilated 52 remote muscle, and portended higher late mortality, since volume is the 53 surrogate for survival after ischemic cardiac dilation (20). 54 55 Conceivably, the sphere shaped end point and functional results in this study 56 57 might become the starting point for a new procedure, if these results are 58 subsequently compared against rebuilding a conical chamber. If this approach is 59 60 61 62 63 4 64 65 1 2 3 4 selected, new data that also includes control normal tagging data could 5 6 simultaneously test how the each procedure restored normal function. 7 8 Influence of Shape on Function 9 10 The current recommendation to use a patch differs from concepts that non patch 11 12 methods are preferable. One potential reason for this selection includes 13 reduction of wall tension during patch placement into the fragile muscle within an 14 akinetic segment containing trabecular scar. I suspect ventricular shape will 15 become the vital surgical consideration, but subsequent functional studies are 16 needed to determine if such decisions are related to patches (Dacron, 17 18 or a flap of transmurally scarred muscle) or ventricular form. The 19 normal elliptical spatial configuration relates to how the remaining fibers are 20 oriented, and my suspicion is that creating a geometric change in fiber direction 21 toward normal will become the endpoint that defines ultimate functional recovery. 22 23 24 25 The authors document how reconstruction changes in systolic and diastolic 26 volume, and comment upon how it affects the Starling relationship. A form 27 function relationship exists, so the shape influence upon fiber orientation will 28 29 impact function at rest and during exercise, as shown by Sallin (6) and Ingels (7). 30 This investigative team previously used diffusion tensor MRI analysis to 31 determine whether the helical fiber orientation of the normal heart geometry is 32 changed when this model of heart failure dilates ventricle and after restoration 33 34 rebuilds cardiac structure (21). A control group was included in that study to 35 properly respond to my principal objection to this report , but that report 36 evaluated the unloaded, decompressed , non functioning heart and thus failed to 37 determine if the stretch of disease a) changed fiber direction and b) could 38 rebuilding restored the natural helical design that underlies the living heart’s 39 40 function.(22). 41 42 A basic anatomic concept of heart failure is that the dilated heart becomes 43 spherical through a change in the radius of curvature within the ventricular wall. 44 45 The currently reported functional analysis of improvement remote muscle systolic 46 circumferential shortening implies the authors might consider repeating their 47 prior MRI study and re-analyze, using the reported dilated chamber dimensions. 48 Such a study would determine if the normal helical configuration is changed by 49 infarction and restored by LV rebuilding, as well as if changes from an elliptical to 50 51 a spherical fiber orientation altered function and then determine if changing fiber 52 orientation would further improve deformation. 53 54 55 56 57 Recovery Timing Evaluation 58 59 60 61 62 63 5 64 65 1 2 3 4 The discussion suggests evaluations at a longer than 6 week recovery period 5 6 may be needed, and subsequent changes may relate to repair of the collagen 7 sheathing of myocytes where the half life of collagenase is 120 days (23). 8 Recovery of neuro endocrine markers towards normal after longer intervals 9 following ventricular volume reduction by LV restoration were recently reported 10 from the Cleveland Clinic (24) and Japan (25) . Timing of functional evaluation 11 12 may have important impact, since withdrawal of these neuro endocrine adaptive 13 forces after stretch may explain the reported clinical change of pressure volume 14 relationships following 4 months of decompression in a study that did not collect 15 biochemical values (26). Perhaps future studies may harvest these biochemical 16 markers at longer follow up intervals, compare them against the current spherical 17 18 post operative shape, and against rebuilding a more conical configuration as 19 shown in Figure 2a and b., and thus become a surrogate for avoiding more 20 complex functional tests. 21 22 23 The role of LV rebuilding is linked to clinical recovery, and consistent with reports 24 showing NYHA status and 6 minute walking tests improve (27) (3). 25 Consequently, their conclusion comment that their study is the first to show the 26 Dor procedure does anything seems a bit cavalier, especially since similar 27 functional clinical findings were reported by Taniguchi in 1999 (28), Kramer in 28 29 2002 (29), and Carmichael from the Cleveland Clinic in 2006 (24). Ventricular 30 shape should be considered with these changes in volume, since energy 31 demands rise with exercise and stress is related to dimensional changes. 32 Consequently, the radius of curvature underlying wall stress rises and is related 33 34 to П R³ in a spherical chamber, but to П R² in a cylinder. Conversely, wall stress 35 falls in the conical heart; deformation increases and efficiency improves as 36 muscle size anisotropically thickens as chamber dimension narrows toward the 37 apex. 38 39 40 In conclusion, the starting point for evaluation for recovery must arise in the 41 normal heart, not the damaged heart. This initiates with understanding normal 42 form and function and avoiding comparisons against the wrong anatomy. This 43 comparison initiates from a proper control data base so that the investigator and 44 45 reader can understand that valid results garnered from starting with a sphere 46 (which is the disease) and subsequently generated by a smaller sphere 47 (following restoration) conveys an abnormal geometry based end point. 48 Returning toward normal in both the operating room and the experimental 49 laboratory will yield evaluation measurements that more closely shall define how 50 51 our interventions work. 52 53 54 55 56 57 58 59 60 61 62 63 6 64 65 1 2 3 4 5 6 7 Figure Legends 8 9 10 11 12 Figure 1 The left image shows cardiac shape in the normal heart, with a conical 13 or elliptical chamber. The right image shows a dilated failing heart with a 14 spherical shape. 15 16 17 Figure 2 a) The left image shows of the spherical dilated cardiac patient with an 18 anterior infarction, taken from the 2002 MRI tagging report by Kramer and 19 associates(30). The right image shows how left ventricular rebuilding restored a 20 conical left ventricular shape. 2 b) The left image shows is the experimental post 21 infarction shape appearing in the report by Zhang (1), displaying the same 22 23 spherical preoperative cardiac shape appearing in 2a displaying the pre 24 operative clinical image. The right image in 2b shows that the postoperative 25 volume is reduced, but the cardiac shape remains spherical, and continues to 26 mirror the left image pre operative configuration in both the clinical and 27 28 experimental study. 29 30 Figure 3 31 Comparison of treatment of the dilated ischemic cardiomyopathy (above) by 32 addressing the disease (lower left) and leaving a spherical shape, or doing 33 34 the SAVE of Pacopexy (18) (lower right) and rebuilding an elliptical shape. 35 Note that the patch is placed into the septum that does not have scar, and 36 the point of placement is above the scarred region in mid septum. 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 7 64 65 1 2 3 4 Reference List 5 6 7 (1) Zhang P, Guccione JM, Nicholas S, Walker J, Crawford P, Shamal A et al. 8 9 Endoventricular patch plasty for dyskinetic anteroapical left ventricular 10 11 12 increases systolic circumferential shortening in sheep (v) (E). Journal of Thoracic 13 14 and Cardiovascular Surgery 2007; In press. 15 16 17 18 (2) Dor V, Di Donato M, Sabatier M, Montiglio F, Civaia F. Left ventricular 19 20 reconstruction by endoventricular circular patch plasty repair: a 17-year 21 22 experience. Semin Thorac Cardiovasc Surg 2001; 13(4):435-447. 23 24 25 26 (3) Athanasuleas CL, Buckberg GD, Stanley AW, Siler W, Dor V, Di Donato M et al. 27 28 Surgical ventricular restoration in the treatment of congestive heart failure due to 29 30 31 post-infarction ventricular dilation. J Am Coll Cardiol 2004; 44(7):1439-1445. 32 33 34 (4) Bernard C. An Introduction to the Study of Experimental Medicine. New York: 35 36 37 Dover Publications, 1957. 38 39 40 (5) Buckberg GD. Congestive heart failure: treat the disease, not the symptom--return 41 42 43 to normalcy. J Thorac Cardiovasc Surg 2001; 121:628-637. 44 45 46 (6) Sallin EA. Fiber orientation and ejection fraction in the human ventricle. 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Improved health-related quality of life and functional 42 43 44 status after surgical ventricular restoration. Ann Thorac Surg 2006; In press. 45 46 47 (28) Taniguchi K, Sakurai M, Takahashi T, Imagawa H, Mitsuno M, Nakano S et al. 48 49 50 Postinfarction left-ventricular aneurysm: regional stress, function, and remodeling 51 52 after aneurysmectomy. Thorac Cardiovasc Surg 1998; 46(5):253-259. 53 54 55 56 57 58 59 60 61 62 63 11 64 65 1 2 3 4 (29) Kramer CM, Magovern JA, Rogers WJ, Vido D, Savage EB. Reverse remodeling 5 6 7 and improved regional function after repair of left ventricular aneurysm. J Thorac 8 9 Cardiovasc Surg 2002; 123(4):700-706. 10 11 12 13 (30) Kramer CM, Magovern JA, Rogers WJ, Vido D, Savage EB. Reverse remodeling 14 15 and improved regional function after repair of left ventricular aneurysm. J Thorac 16 17 18 Cardiovasc Surg 2002; 123(4):700-706. 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 12 64 65 Figure 1 Click here to download high resolution image Figure 2 Click here to download high resolution image Figure 3 Click here to download high resolution image