Left Ventricular Mass Regression Early After Aortic Valve Replacement

Transcription

1 Left Ventricular Mass Regression Early After Aortic Valve Replacement George T. Christakis, MD, Campbell D. Joyner, MD, Christopher D. Morgan, MD, Stephen E. Fremes, MD, Karen J. Buth, MSc, Jeri Y. Sever, Vivek Rao, MD, Kostas P. Panagiotopoulos, MD, Patricia M. Murphy, MD, and Bernard S. Goldman, MD Divisions of Cardiovascular Surgery, Cardiology, and Anesthesia, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada Background. Regression of left ventricular hypertrophy is an important and well-recognized salutary effect of aortic valve replacement. The earliest evidence of left ventricular mass regression after aortic valve replacement and the influence of prosthesis type are not well known, and were the focus of this study. Methods. Transthoracic echocardiography was used to measure left ventricular mass index preoperatively and before discharge in 57 consecutive patients undergoing isolated aortic valve replacement (with or without coronary artery bypass grafting). Results. Three patients were excluded from the study because of inability to obtain accurate M-mode echocardiographic images for left ventricular mass measurement preoperatively (1) or postoperatively (2). Of the remaining 54 patients, mechanical bileaflet valves were used in 19, stented tissue bioprostheses were implanted in 15, and a stentless porcine bioprosthesis was chosen for 20. Postoperative echocardiograms were obtained 4.9 ± 2.3 days after aortic valve replacement (range, 2 to 9 days). A two-way repeated-measures analysis of variance demonstrated a significant reduction of left ventricular mass index before discharge (preoperative ± 45.2 g/m 2, postoperative g/m2; p = ) but no differences between prostheses. Conclusions. Left ventricular mass regression begins early after aortic valve replacement, probably because of reduction of transvalvular gradients and left ventricular wall stress. At least in the very early postoperative period, the type of prosthesis does not influence the extent of mass regression. (Ann Thorac Surg 1996;62:1084-9) eft ventricular hypertrophy produced by the pressure L or volume overload of aortic valve disease is a beneficial adaptation that compensates for high intracavitary pressures [1]. Aortic valve replacement results in a significant reduction of transvalvular gradients [2, 3] and is accompanied by at least partial regression of left ventricular hypertrophy [4-6]. Regression of left ventricular mass after aortic valve replacement may reduce the long-term complications of sudden death and congestive heart failure associated with left ventricular hypertrophy [7-9]. The time course and earliest evidence of significant left ventricular mass regression after aortic valve replacement are controversial and range from days [10] to 1 year [11]. Differences in the rates of regression of left ventricular hypertrophy among various prostheses are unknown. This study was designed to assess the extent of left ventricular mass regression at the time of hospital discharge after aortic valve replacement and to evaluate the influence of various aortic valve prostheses on left ventricular hypertrophy. Presented at the Poster Session of the Thirty-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29-31, Address reprint requests to Dr Christakis, Division of Cardiovascular Surgery', Sunnvbrook Health Science Centre, 2075 Bayview Ave, H406, Toronto, Ont, Canada M4N3M5. Material and Methods Patient Population Fifty-seven consecutive patients undergoing isolated aortic valve replacement (with or without coronary artery bypass grafting) at Sunnybrook Health Science Centre between August 1, 1994 and March 1, 1995 were evaluated prospectively. All clinical and echocardiographic data describing this population were prespecified and collected prospectively. Patients who had implantation of the investigational Toronto Stentless Porcine Valve (SPV) (St. Jude Medical, St. Paul, MN) signed a consent form approved by our Institutional Review Board. The choice of valve prosthesis was made preoperatively after consultations among the cardiac surgeon, cardiologist, and the patient. Clear M-mode imaging of the heart was not possible in 1 patient preoperatively and in 2 patients postoperatively. The remaining 54 patients, in whom measurements were possible, were included in the study. Operative Technique Cardiopulmonary bypass was instituted with ascending aortic and two-stage single atrial cannulation. Moderate hemodilution and mild systemic normothermia (>33 C) were used. A left ventricular vent was inserted through the right superior pulmonary vein. Myocardial protection was initiated with a single dose of high-potassium blood cardioplegia through the ascending aortic root to induce 1996 by The Society of Thoracic Surgeons /96/$15.00 Published bv Elsevier Science lnc PII S (96)

2 Ann Thorac Surg CHRISTAKIS ET AL ;62: LEFT VENTRICULAR MASS REGRESSION cardiac arrest. This was followed by continuous antegrade warm (n = 12) or cold (n - 35) oxygenated blood cardioplegia using direct cannulation of each coronary ostium, or continuous retrograde blood cardioplegia (n 7). A transverse aortotomy was performed approximately 5 cm above the aortic annulus. The native aortic valve was excised completely, and the annulus, aorta, and anterior leaflet of the mitral valve were extensively debrided of calcium when it was present. Annular and sinotubular junction sizing of the SPV and conventional valves has been documented previously [12]. All mechanical and stented tissue valves were implanted using interrupted mattress and pledgeted 2-0 Ticron sutures (Davis & Geck, Danbury, CT). All pledgets were placed in the subannular position. In the noncoronary cusp, sutures were placed from outside the aorta to accommodate a larger prosthesis. The insertion technique for the SPV has been reported by our group [12]. The base of the SPV was sutured in the annular position using interrupted single 4-0 Ticron sutures circumferentially. The commissure and sinuses of the SPV were sutured to the aorta using three continuous running 4-0 Prolene sutures (Ethicon, Somerville, NJ). Mechanical valves consisted of CarboMedics (Austin, TX) (n = 16) and St. Jude Medical (St. Paul, MN) (n - 3) valves. Stented tissue bioprostheses consisted of the Hancock II standard (Medtronic Inc, Minneapolis, MN) (n - 9) and the Carpentier-Edwards pericardial (Baxter Healthcare Corp, Irvine, CA) (n - 6) valves. Measurenlents All patients underwent transthoracic echocardiography within 1 week before operation and 1 or 2 days before discharge after aortic valve replacement. Effective orifice area, peak and mean pressure gradients, and left ventricular mass index were measured preoperatively (Appendix 1). Only left ventricular mass index was measured in the early postoperative period. All patients had complete preoperative and postoperative measurements of left ventricular mass, thus allowing paired analysis of the results. Echocardiographic Studies A Hewlett-Packard Sonos 1000E (Hewlett-Packard Inc, Palo Alto, CA) with a 2.5-MHz transducer was used for echocardiographic assessment. The examination included 2-dimensional, 2-dimensional derived M-mode, continuous wave and pulsed Doppler, and color Doppler studies. Standard left parasternal, apical, right parasternal, subcostal, and suprasternal views were obtained in a step-by-step successive pattern of interrogation. Left ventricular mass was calculated from 2-dimensional derived M-mode measurements taken according to the American Society of Echocardiography recommendations. Each measurement was averaged from three cardiac cycles in sinus rhythm and six cardiac cycles in atrial fibrillation. The postoperative measurements were made without knowledge of the preoperative values. Only two experienced sonographers with interobserver variability documented at less than 5% were employed for this study. Statistical Analysis Postoperative left ventricular mass regression was prespecified as the primary outcome in this study. Two-way repeated-measures analysis of variance was used to assess the influence of time and prosthesis type on left ventricular mass index and left ventricular dimensions. Perioperative demographic characteristics of each prosthesis group were compared using X 2 test for categoric variables and analysis of variance for continuous variables. Continuous data in the text and tables are presented as mean _+ standard deviation; standard error bars are used in the figure. Results There were no postoperative deaths. One patient who received an SPV and 2 patients who received a stented tissue valve required an intraaortic balloon pump postoperatively. One patient with an SPV had a transient reversible neurologic deficit postoperatively. Perioperative clinical variables describing the patient population are given in Table 1. Patients receiving stented tissue valves were older than the other valve groups and tended to have a higher prevalence of coronary artery, disease and diabetes preoperatively. Patients who received the SPV had a higher percentage of large valve sizes implanted. The average valve size inserted was 26.6 _+ 2.0 mm for the SPV, compared with 24.3 _+ 3.1 mm for the stented tissue valves and _ 2.1 mm for the mechanical valves (p < 0.05). Effective orifice area, peak pressure gradient, and mean pressure gradient measured preoperatively are shown in Table 2. Table 3 depicts the left ventricular dimensions used to calculate left ventricular mass. There was a nonsignificant reduction in left ventricular end-diastolic dimension (p : 0.09), interventricular septal wall thickness (p ), and posterior left ventricular wall thickness (p = 0.06) postoperatively when all valves were combined. Postoperative transthoracic echocardiography was performed at a mean of days after aortic valve replacement (range, 2 to 9 days). Figure 1 illustrates the preoperative and postoperative left ventricular mass index values for the entire patient population and for each prosthesis group. There was no significant difference among valve prostheses for left ventricular mass index at baseline or at the postoperative follow-up. Two-way repeated-measures analysis of variance demonstrated a significant reduction in left ventricular mass index from the preoperative to postoperative period (p = ), but no differences were seen among prosthesis groups (p = 0.43). Comment Aortic valve replacement increases long-term survival, reduces symptoms, and improves the quality of life in patients with aortic valve disease. Left ventricular hyper-

3 1086 CHRISTAKIS ET AL Ann Thorac Surg LEFT VENTRICULAR MASS REGRESSION 1996;62: Table 1. Perioperative Clinical information" Mechanical Stented Tissue Toronto Characteristic All Valves Valves Valves SPV No. of cases Mean age (y) 63.2 _ _~ " 60.6 _ Age.>-70 y (%) b 20.0 Body surface area (m 2) @ Female (%) NYHA class III or IV (%) Urgent operation (%) Reoperation (%) Preoperative LVEF <0.40 (o,,) Corona D, artery, disease (%) Diabetes (%) Hypertension (%) Congestive heart failure (%) Preoperative aortic valve lesion (%) Stenosis ~ Regurgitation CABG (%) Valve size in mmd (9) 26.3 (5) 26.7 (4) 0 (0) (13) 26.3 (5) 33.3 (5) 15.0 (3) (10) 31.6 (6) 6.7 (1) 15.0 (3) (14) 15.8 (3) 13.3 (2) 45.0 (9) (8) 0 (0) 20.0 (3) 25.0 (5) Postoperative ventilation (h) 17.7 _ ~ Postoperative hospital stav (d) 8.1 _ _ _ _+ 2.4 Data are presented as n, %, or mean + standard deviation, b p < 0.05, stented versus mechanical and SPV groups. ~ p < 0.05, mechanical versus stented and SPV groups, a Percentage implanted (number of patients). CABG coronary arter T bypass grafting; LVEF - left ventricular ejection fraction; NYHA = New York Heart Association; SPV = Stentless Porcine Valve. trophy regresses after aortic valve replacement, but left ventricular mass does not return to normal levels [13]. The time course of the regression of left ventricular hypertrophy after aortic valve replacement is controversial. The earliest documented evidence of consistent left ventricular mass regression after aortic valve replacement has varied between 6 weeks [10] and 1 year ]11]. The earliest time at which left ventricular mass regression is possible after aortic valve replacement and the influence of the prosthesis type on left ventricular hypertrophy are unknown, and were the focus of this study. Importance qf Left Ventricular Hypertrophy The myocardial response to pressure or volume overload imposed by aortic valve disease is left ventricular hypertrophy. Hypertrophy is characterized by a concentric increase in muscle mass to preserve a normal relation between systolic wall stress and ejection fraction [1]. Table 2. Preoperative Measurements qf Effective Or(rice Area and Pressure Gradients" All Mechanical Stented Tissue Characteristic Valves Valves Valves Toronto SPV Number of cases Effective orifice area (cm 2) Peak pressure gradient (mm Hg} Mean pressure gradient (ram Hg) ~: ~ 28 t' ~ ff " Data are presented as n or mean - standard deviation stented group. SPV Stentless Porcine Valve. b l; < 0.05, mechanical versus stented and SPV groups. p ~ 0.05, mechanical versus

4 Ann Thorac Surg CHRISTAKIS ET AL ;62: LEFT VENTRICULAR MASS REGRESSION Table 3. Preoperative and Postoperative Left Ventricular Dimensions '~ All Valves (n 54) Left ventricular end-diastolic dimension (mm) Interventricular septal wall (turn) Left ventricular posterior wall (mm) -' Data are presented as mean + standard deviation, Preoperative Measurements Postoperative Measurements _ b Postoperative preoperative measurements. Delta b P Value Regression of left ventricular hypertrophy after aortic valve replacement is an important end point. All prosthetic valves are relatively stenotic because the valve sewing ring and stents reduce the effective orifice area. After aortic valve replacement, transvalvular gradients often remain elevated, and left ventricular hypertrophy does not resolve completely [13]. Evidence from the hypertension literature indicates a strong correlation between left ventricular hypertrophy and sudden death, congestive heart failure, myocardial infarction, and cardiovascular mortality [14, 15]. Ghali and associates [16] demonstrated that patients with even moderate left ventricular hypertrophy had a greater risk of death from any cause (even after adjustment for age, sex, coronary artery disease, and hypertension). Concerns about the longterm effects of residual hypertrophy after aortic valve replacement have been raised by various investigators [7-9[. Late deaths after aortic valve replacement are often caused by sudden cardiac arrest, arrhythmias, and congestive heart failure [7-9]. These late events may be caused by or influenced by left ventricular hypertrophy. Left ventricular mass regression after aortic valve replacement may be an important and underestimated determinant of long-term outcome. Left Ventricular Mass Regression Echocardiographic mass measurements are noninvasive and reproducible estimates of the extent of left ventric- ular hypertrophy. M-mode echocardiography has been shown to correlate well with contrast left ventriculography for left ventricular mass measurement. Devereux and Reichek [17] estimated antemortem human left ventricular mass with M-mode echocardiography and compared their values with postmortem mass. They found a good correlation (r = 0.98) between estimated and actual left ventricular mass. Left ventricular mass measurements have been used to demonstrate regression of hypertrophy in experimental [18] and clinical studies [19] of the treatment of hypertension. Left ventricular mass reflects the severity of aortic stenosis, is positively correlated with peak aortic valve gradients [20], and has been used to confirm at least partial regression of hypertrophy after aortic valve replacement [13]. The extent and time course of left ventricular mass regression after valve replacement remain controversial. Kennedy and colleagues [21] and others [13] used catheterization techniques to assess 11 to 24 patients with preoperative aortic stenosis and reported left ventricular mass regression after aortic valve replacement ranging between 28% and 38% at mean follow-up times ranging from 18-6 to 22 _+ 8 months. At later mean follow-up times ranging from 56 _+ 23 to 96 _+ 31 months, they reported left ventricular mass regression ranging from 47% to 60%. Kurnik and colleagues [4], using ultrafast computed tomography, reported 27% regression of left ventricular mass at 4 months after aortic 0 U) , I BI All Valves [] Mechanical [7 Stented Tluue i~l Toronto SPV p=o.o008 Fig 1. Preoperative (preop) and postoperative (postop) left ventricular (LV) mass index for the entire patient population and for each prosthesis group. There was no significant difference among valve prostheses for h;ft ventricular mass index at baseline or at postoperative follow-up. A two-way repeated-measures analysis of variance demonstrated a significant reduction in l~ft ventm'cular mass index from the preoperative to postoperative periods (p ) but no difference among prosthesis groups (p = 0.43). (Echo = echocardiography; SPV = Stentless Porcine Valve.) >, o n = Preop Echo Postop Echo

5 1088 CHR STAKIS ET AL Ann Thorac Surg LEFT VENTRICULAR MASS REGRESSION 1996;62: valve replacement and a total of 36% regression at 8 months. Panidis and associates [11], using echocardiography, demonstrated a nonsignificant 10% regression at less than 6 months and a significant 34% regression at greater than 6 months. However, Henry and associates [6] demonstrated a 16% mass reduction at 6 months after aortic valve replacement for aortic stenosis, with no further changes at I year. They observed that most of the regression occurred within the first month after operation. St. John Sutton and associates [10] examined 16 patients by echocardiography and documented a 30% regression of left ventricular mass in days, thus confirming that the majority of mass regression occurs early after aortic valve replacement. We have concluded in this study that there is significant left ventricular mass regression of 10% within 4.9 _+ 2.4 days of operation. The amount of mass regression actually may have been underestimated. In the early period after aortic valve replacement, there may be substantial edema in the tissues, especially myocardial tissue, and this may artificially increase left ventricular dimensions. We examined the influence of prosthesis type on the regression of left ventricular hypertrophy after operation. Although patient selection and different valve sizes prevented direct comparisons of the valves in this study, we documented a consistent and similar regression for all three valve types. The reduction in afterload early after aortic valve replacement was more significant than the relatively smaller residual gradient differences among valves, which may account for the similar extent of early left ventricular mass regression. To study differences among valves, mass measurements must be examined at later times. As well, valves should be compared by annulus size, valve type, and aortic lesion. It would be expected that incomplete left ventricular mass regression would be especially evident in small aortic roots. However, evidence of incomplete regression exists even with appropriately large valves. Monrad and associates [13] assessed 11 patients after aortic valve replacement for aortic stenosis and demonstrated that left ventricular mass regressed from 158 _+ 33 g/m 2 preoperatively to 114 _+ 27 g/m 2 at months postoperatively, compared with 85 _~ 9 g/m 2 for control patients. The prostheses used in the study by Monrad and associates [13] included two 27-mm tissue valves and nine Bjork-Shiley valves with an average size of ram. Pantely and colleagues [5] assessed 10 patients with aortic stenosis who had the relatively obstructive Starr-Edwards mechanical valve implanted, and measured a left ventricular mass index of g/m 2 at 20 months' mean follow-up. However, mass regression after aortic valve replacement is dependent on a host of factors. Persistence of myocardial collagen fibrosis may account for some of the incomplete regression. Age, sex, hypertension, coronary artery, disease, left ventricular function, and diabetes also may be determinants of left ventricular mass. In this study, we have demonstrated that left ventricular mass regression begins early after aortic valve replacement. We have shown that at least in the very early postoperative period, the type of prosthesis does not influence the extent of left ventricular mass regression. The conclusions from this study, however, are restricted by potential limitations of the study design. There was an absence of other hemodynamic correlates such as gradients, valve areas, and left ventricular function. Furthermore, we studied a mix of patients with aortic stenosis and regurgitation as well as various different types and sizes of prostheses. Finally, patient selection was used; this was not a randomized trial. Further studies are necessary to identify the time course and determinants of left ventricular mass regression after aortic valve replacement. This study was supported by grant B2317 from the Heart and Stroke Foundation of Ontario. References 1. Grossman W. Cardiac hypertrophy: useful adaptation or pathologic process? Am J Med 1980;69: Cosgrove DM, Lvtle BW, Gill CC, et al. In vivo hemodynamic comparison of porcine and pericardial valves. J Thorac Cardiovasc Surg 1985;89: David TE, Armstrong S, Sun Z. Clinical and hemodynamic assessment of the Hancock II bioprosthesis. Ann Thorac Surg 1992;54: Kurnik PB, Innerfield M, Wachspress JD, Eldredge WJ, Waxman HL. Left ventricular mass regression after aortic valve replacement measured by ultrafast computed tomography. Am Heart J 1990;120: Pantely G, Morton M, Rahimtoola SH. Effects of successful, uncomplicated valve replacement on ventricular hypertrophy, volume, and performance in aortic stenosis and in aortic incompetence. J Thorac Cardiovasc Surg 1978;75: Henry, WL, Bonow RO, Borer JS, et al. Evaluation of aortic valve replacement in patients with valvular aortic stenosis. Circulation 1980;61: He GW, Grunkemeier GL, Gately HL, Furnary AP, Starr A. Up to thirty-year survival after aortic valve replacement in the small aortic root. Ann Thorac Surg 1995;59: Lund O, Pilegaard HK, Magnussen K, Knudsen MA, Nielsen TT, Albrechtsen OK. Long-term prosthesis-related and sudden cardiac-related complications after aortic valve replacement for aortic stenosis. Ann Thorac Surg 1990;50: Lvfle BW, Cosgrove DM, Taylor PC, et al. Prima~ isolated aortic valve replacement: early and late results. J Thorac Cardiovasc Surg 1989;97: St. John Sutton M, Plappert T, Spiegel A, et al. Early postoperative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: a prospective two-dimensional echocardiographic study. Circulation 1987;76: Panidis IP, Kotler MN, Ren JF, Mintz GS, Ross J, Kalman P. Development and regression of left ventricular hypertrophy. J Am Coll Cardiol 1984;3: Del Rizzo DF, Goldman BS, Joyner C, Sever J, Fremes SE, Christakis GT. Initial clinical experience with the Toronto Stentless Porcine Valve TM. J Cardiac Surg 1994;9: Monrad ES, Hess OM, Tomoyuki M, Nonogi H, Corin WJ, Krayenbuehl HP. Time course of regression of left ventricular hypertrophy after aortic valve replacement. Circulation 1988;77: Bikkina M, Larson MG, Levy D. Asymptomatic ventricular arrhythmias and mortality, risk in subjects with left ventricular hypertrophy. J Am Coll Cardiol 1993;22:

6 Ann Thorac Surg CHRISTAKIS ET AL ;62: LEFT VENTRICULAR MASS REGRESSION 15. Levy D. Clinical significance of left ventricular hypertrophy: insights from the Framingham Study. J Cardiovasc Pharmacol 1991;17(Suppl 2):$ Ghali JK, Liao Y, Simmons B, Castanet A, Cao G, Cooper RS. The prognostic role of left ventricular hypertrophy in patients with or without coronary artery, disease. Ann Intern Med 1992;117: Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977;55: Pegram BL, [shise S, Frohlich ED. Effect of methyldopa, clonidine and hydralazine on cardiac mass and hemodynamics in Wistar Kyoto and spontaneously hypertensive rats. Cardiovasc Res 1982;16: Rowlands DB, Glover DR, Ireland MA, et al. Assessment of left ventricular mass and its response to antihypertensive treatment. Lancet 1982;2: Salcedo EL, Korzick DH, Currie PJ, Stewart wj, Lever HM, Goormastic M. Determinants of left ventricular hypertrophy in patients with aortic stenosis. Cleve Clin J Med 1989;56: Kennedy JW, Doces J, Stewart DK. Left ventricular function before and following aortic valve replacement. Circulation 1977;56: Appendix 1 Calculations 1. EFFECTIVE ORIFICE AREA. Effective orifice area was calculated by reconfiguration of the continuity, equation: EOA (CSAf.w> T x TVl~v~>r)/T~lao, where EOA effective orifice area in cma; CSAI.vo T cross= sectional area of the left ventricular outflow tract in cm 2 obtained using 2-dimensional measurement of the left ventricular outflow tract diameter; TVli_w) I veloci~, time integral of forward blood flow in cm, derived from the pulsed-wave Doppler study obtained in the left ventricular outflow tract; and TVIAo -- velocity time integral of forward blood flow in cm, derived from the software integration of transvalvular continuous-wave Doppler. 2. PEAK PRESSURE GRADIENT. Peak velocities, obtained from pulsed-wave and continuous-wave Doppler, were converted to peak pressure gradient using Bernoulli's equation: ~PPEAK 4 (V22 -- V12), where -~PPEAK -- peak systolic aortic pressure gradient in mm Hg; V z -~ prosthetic peak velocity in m/s, measured with continuous-wave Doppler; and V 1 peak velocity proximal to valve in m/s, measured with pulsed-wave Doppler. 3. MEAN PRESSURE GRADIENT. Mean transvalvular pressure gradient was calculated by subtraction of the mean pressure proximal to the valve from the mean distal pressure: &PMEAN ~ P2 P1, where &PMEAN mean transvalvular pressure gradient in mm Hg; P2 - prosthetic mean pressure measured with continuouswave Doppler; and P~ - proximal mean pressure measured with pulsed-wave Doppler in the left ventricular outflow tract. 4. LEFT VENTRICULAR MASS INDEX, Left ventricular mass was calculated by the ASE cube method: LVM [{LVED ± WS + LVPwALL )3 -- (LVED) 3] + 0.6, where LVM left ventricular mass in g; LVED = left ventricular end-diastolic dimension in cm; IVS interventricular septal wall thickness in cm; and LVPwALE thickness of the left ventricular posterior wall in cm. Left ventricular mass was indexed by body surface area: height in cm body weight in kg BSA = \ - 3,600 ' where BSA = body surface area in m 2.