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Eur J Cardiothorac Surg 2001;19:797-805
© 2001 Elsevier Science NL

Left ventricular architecture after valve replacement due to critical aortic stenosis: an approach to dis-/qualify the myth of valve prosthesis–patient mismatch?

Igor Kneza, Rainer Rienmüllerb, Robert Maierc, Peter Rehakd, Brigitte Schröttnerb, Heinrich Mächlera, Michael Anelli-Montia, Bruno Riglera

a Division of Cardiac Surgery, Karl Franzens University and Medical School of Graz, Graz, Austria
b Division of Radiology, EBT, Karl Franzens University and Medical School of Graz, Graz, Austria
c Division of Cardiology, Karl Franzens University and Medical School of Graz, Graz, Austria
d Division of Biomedical Engineering and Computing, Karl Franzens University and Medical School of Graz, Graz, Austria

Received 11 October 2000; received in revised form 8 March 2001; accepted 13 March 2001.

Corresponding author. Tel.: +43-316-385-4671; fax: +43-316-385-4672
e-mail: igor.knez{at}kfunigraz.ac.at


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
 References
 
Objectives: Left ventricular hypertrophy in patients with critical aortic stenosis (AS) is an adaptive process that compensates for high intracavitary pressure and reduces systolic wall stress followed by an increase in myocardial masses. In the present prospective clinical trial, we investigated long-term compensatory changes in left ventricular geometry and function after aortic valve replacement using mechanical bileaflet prostheses with the main emphasis on the small-sized aortic annulus and valve prosthesis–patient mismatch. Methods: A total of 58 patients with critical AS were assigned to the following groups according to the predictive value of prosthetic valve area index (VAI): group EXMIS: 29 patients (VAI<=0.99), expected mismatch; group NOMIS: 29 patients (VAI<=0.99), no mismatch. At controls T0 (before operation/operation (OP), T1 and T2 (4 and 20 months after OP) the left ventricular geometry was recorded by means of Imatron® electron beam tomography and the transprosthetic velocities were measured by echocardiography. Results: Statistical analysis showed a consistent reduction in the absolute (P=0.04) and indexed (P=0.04) left ventricular myocardial mass for both cohorts; furthermore, there was a significant difference between EXMIS and NOMIS patients concerning the factors, time and mass reduction (P=0.005), because of distinct baselines. A logistic regression report revealed preoperative cardiac output, absolute left ventricular myocardial mass, perfusion, body surface area and the native valve orifice area as predicting coefficients and factors for a minimum mass reduction of 25%. We explain a mathematical formula that turned out to be the most sensitive for correctly classified factors. Conclusions: The left ventricular geometry and transprosthetic velocities resulted in the same postoperative recovery for both EXMIS and NOMIS patients. The presented data showed that valve prosthesis–patient mismatch had no influence in several stepwise logistic regression models. We conclude that modern mechanical bileaflet prostheses allow both acceptable hemodynamics and recovery of left ventricular hypertrophy, even in small aortic annuli.

Key Words: Aortic valve replacement • Regression of left ventricular myocardial mass • Valve area index • Effective valve orifice area • Mechanical bileaflet prosthesis


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
 References
 
From the surgeon's point of view, aortic valve replacement (AVR) for critical aortic stenosis (AS) in the presence of a small-sized aortic annulus tends to be problematic. The surgical literature abounds with approaches to the ‘annulus’ of arterial valves and with accounts of optimal techniques of enlarging this anatomically well defined structure [1]. A small aortic root (SAR) was traditionally seen as one into which a prosthesis sizer with a diameter of 21 mm would not fit during intraoperative assessment. However, the first reports argued that the problem of ‘valve prosthesis–patient mismatch’ is present whenever the implanted prosthetic valve area is less than that of the patient's native aortic valve [2]. Additionally, postoperative data indicate that an increase of rest and exercise transvalvular pressure gradients through normally functioning prosthetic valves appears to be related to this term designated as mismatch between the prosthesis geometric orifice area or effective orifice area (EOA) and the patient's body surface area (BSA) [3]. Data from in vitro experiments suggested that the indexed prosthetic valve area should ideally not be less than 0.90–1.00 cm2/m2 BSA for aortic prostheses, in order to minimize residual postoperative transprosthetic peak pressure gradients, which may hinder or delay the regression of left ventricular hypertrophy [4]. Reflecting on clinical routine, these facts may result in persistent symptoms of AS, i.e. a higher incidence of arrhythmias and impaired left ventricular function, causing an increased risk of sudden death [5]. As a consequence, the surgeon has to decide intraoperatively if an aortic annulus enlarging procedure is necessary when a valve prosthesis–patient mismatch could be anticipated [6]. It is more than difficult to predict when to enlarge the aortic annulus – exposing the patient to higher perioperative risks – for any given valve substitute, patient BSA and physical capacities. Recently published studies illustrate that there is a tendency to relativize the influence of valve prosthesis–patient mismatch after AVR with modern small-sized prostheses as far as long-term morbidity and mortality are concerned [7–9]. As myocardial masses and cardiac filling volumes are very specific and sensitive markers for the assessment of left ventricular dysfunction, we defined the hypothesis – with respect to normal left ventricular masses in healthy humans, to narrow annulus diameters and to small-sized prostheses with reduced geometric orifice areas and EOAs – that a minimum mass regression of 25% (i.e. normalization) and a significant decrease of loading volumes should evolve into a steady state at least 4 months following the AVR.

In ‘phase I’ of the present study, our aim was to analyze the following key questions by a prospective, randomized, ethics committee approved clinical trial: (1), how do the main factors, left ventricular mass, myocardial diameters and loading volumes, basically react after valve replacement with a modern bileaflet mechanical prosthesis due to critical AS; (2), is there a significant influence of valve prosthesis–patient mismatch on regression of left ventricular mass; (3), to which degree are demographic and hemodynamic cofactors responsible for significant interactions; (4), and finally, is there a way to establish a mathematical formula that could imply patients’ variables to predict outcomes of mass regression curves after AVR with modern bileaflet mechanical valves?


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 Appendix A. Conference...
 References
 
2.1. Patients
Between December 1996 and December 1998, a total of 287 adult patients requiring elective aortic valve operations (with/without concomitant procedures) were admitted to our unit. Those who did not meet the inclusion criteria, 165 patients, were primarily excluded from the study, and 31 patients refused to enter the study protocol. The primary exclusion criteria were: supposed allergy against ionic contrast agent, essential arterial hypertension, critical aortic valve stenosis with restricted left ventricular function (ejection fraction of <50%) and/or a maximum transvalvular pressure gradient of {Delta}PGmax<70 mmHg, diagnosis of acute endocarditis, the need for reoperation or associated procedures involving the ascending aorta or excessive coronary artery bypass grafting because of coronary multivessel disease and the need for reoperation or concomitant mitral or tricuspid valve procedures.

2.2. Study design and clinical follow-up
Within a period of 24 months, six staff surgeons were assigned to the patients. The patients themselves were not able to be randomly assigned to a surgeon (three staff surgeons performed conventional operations and the other three staff surgeons used an L-shaped ministernotomy approach). Postoperative clinical outcomes among the surgeons were calculated with a quality-control program (Data Ease Version 4.53, Data Ease International, Inc., USA). As we had already shown in an earlier publication, we have not seen any significant differences in more than the last 1000 procedures since 1989. Standardized operation techniques, perioperative intensive management and postoperative care have already been described in previous publications [7,10]. According to the study protocol, the surgeons had to implant the largest possible valve diameter without enlarging the native aortic valve annulus. For this purpose, we selected the latest generation of mechanical bileaflet CarboMedics® prosthetic heart valve (Sulzer CarboMedics, Inc, Austin, TX) referring to its world-wide approval because of hemodynamic characteristics (comparable with other mechanical valve types) and favourable ‘in- and outdoor‘ past performance records [7,11–17]. According to world-wide practice, patients older than 70 years were randomized either to a mechanical bileaflet or to a biological, stent mounted porcine valve (CarboMedics® prosthetic heart valve versus Medtronic Mosaic®, Medtronic, Inc, Minneapolis, MN).

In order to obtain the highest grade of objectivity, we proposed as an appropriate and accessible variable, the predictive value of valve area index (VAI; Eq. (1))

((1))
where GOA (cm2) is the prosthesis geometric orifice area provided by the manufacturer and BSA (m2) is the body surface area of every individual patient [8]. Then, we assigned our patients to the following groups:

Group EXMIS
VAI of <=0.99, expected mismatch.

Group NOMIS
VAI of >0.99, no mismatch.

During preoperative assessment (T0), including a thorough cardiac examination and search for risk factors, all patients had electrocardiography (ECG), Doppler echocardiography, chest X-ray, cardiac catheterization (ventriculography and coronary angiography), carotid artery sonography and ‘Electron Beam Technology®’ (EBT). Postoperatively, all patients were investigated at the control times, T1 (3.6±0.4 months) and T2 (20.7±2.1 months), by means of a standardized questionnaire, ECG, chest X-ray, Doppler echocardiography and EBT.

2.3. Ultrafast computed tomography
A highly reproducible and relevant technique for determining left ventricular mass and left ventricular loading volumes is EBT [18]. Proposing that the left ventricle is a rotating ellipsoid and working with the modified Simpson's rule (acquisition of the sum of individual tomographic masses and volumes at each level of the heart), we used an automated edge detection technique outlining the endocardial and epicardial borders of the left ventricle in systolic and diastolic images from each level. According to the study protocol, calculations were made from ECG triggered EBT scanner Imatron® C-150L (Imatron, Inc, San Francisco, CA) with an effective radiation dose of 9 mSV. After 17–20 native single slice scans, 200–230 ml of non-ionic contrast agent Visipaque® (Nycomed Austria GmbH, Linz, OÖ, Austria) was applied intravenously, multi-slice scans with 50 ms exposure time were acquired to measure the myocardial blood flow and to assess defined functional determinants. All interpretations were made by the same experienced investigator blinded for patient demographic data, times of assessment (T0, T1 and T2) and procedure, and type and diameter of implanted valve prosthesis.

2.4. Doppler echocardiography
Echocardiographic assessment was performed and interpreted in every patient at investigations T0, T1 and T2 by two independent and experienced investigators (also blinded for patient demographics, valve procedure, valve type and diameter) by means of a GE Vingmed 800® ultrasound system with a 3.25 MHz transducer (General Electrics Ultrasound Europe, Horten, Norway). After M-mode assessment of end-diastolic and end-systolic parameters, infravalvular and supravalvular left ventricular outflow tract cross-sectional areas were calculated. Peak velocity was measured by pulsed-Doppler, averaging from three velocity envelopes, and the mean velocity was calculated by on-line averaging of the instantaneous velocities measured throughout the velocity complexes. Measurements were made in triplicate in each stage to ensure reproducibility. The modified Bernoulli equation was used to assess the peak pressure drop (gradient) across the valve prosthesis. As a consequence, the velocity ratio (the quotient of mean subaortic to mean transaortic velocity), stenotic aortic valve and effective orifice areas were calculated using the continuity equation.

2.5. Study endpoints
Prespecification of primary endpoints was focused on data concerning:

Secondary endpoints were also prespecified with emphasis on:

2.6. Statistical analysis
2.6.1. Basics
All data are presented as means±SD. Preoperative patient characteristics, intraoperative data, perioperative data and results collected from cardiac catheterization and EBT were compared between the two groups by Fisher's Exact and Chi-square tests for qualitative variables, respectively; Mann–Whitney U-tests were used for continuous variables. Changes in the defined primary and secondary endpoints were set in relation by analysis of variance for repeated measurements (‘repeated measures ANOVA’) with the factors EXMIS/NOMIS (groups) and postoperative time. Multiple comparisons between the above-mentioned primary and secondary variables at control times were done according to the Tukey–Kramer test. These defined endpoints served as a basis to compare the reduction of absolute and relative left ventricular mass as a function of time with adjustment for differences in baseline variables. Only P values of less than 0.05 were considered significant (P<0.05). All statistical analyses were accomplished using the NCSS 2000 software package (NCSS Statistical Software, Kaysville, UT).

2.6.2. Development of the formula
Identified risk variables were entered into a stepwise logistic regression model to assess the regression coefficient for each factor and to develop an exponential formula for risk equation (Eq. (2))

((2))
where P is the probability of a defined endpoint and X=B0X0+B1X1+...BnXn. Each B value represents a constant associated with a specific variable at risk, and the X values determine the status of the risk variable for any considerable patient.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 Appendix A. Conference...
 References
 
3.1. Baseline variables
By definition, the follow-up period ended on 30th June 2000; for the entire cohort, an adequate data follow-up was analyzed over a 4-year period. In total, 76 patients (31.7%) were eligible for ‘phase I’, 14 patients underwent AVR with a stented porcine valve. Two patients with the mildest subjective symptoms of intolerance of contrast medium were withdrawn. To create a homogeneous study group, we secondarily excluded those 14 patients who had undergone AVR with the stented Mosaic® and included them into ‘phase II’. In summary, 60 patients (31 males and 29 females) were recruited to enter follow-up and statistical analyses, and 58 patients completed the trial. The patient populations grouped by subset model at baselines are summarized in Tables 1 and 2.


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  		Table 1. Comparison of perioperative patient characteristics by groups

 

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  		Table 2. Comparison of primary (I) and secondary (II) endpoint variables by groupsa

 
The groups were matched for demographic and clinical features, left ventricular geometry and hemodynamics. As we expected, intraoperative variables prosthesis diameter (19.9±0.9 vs. 22.1±1.4 mm), geometric orifice area (1.88±0.24 cm2 vs. 2.35±0.38 cm2) and VAI (0.96±0.08 vs. 1.34±0.14) were significantly diminished in group EXMIS (P=0.000001).

3.2. Primary endpoints
We found a clinically consistent reduction in LVMMabs (from 197.7±50.5 to 156.7±29.6 g vs. from 219.8±79.2 to 145.9±46.9 g; PT=0.04) and LVMMindex (from 108.1±23 to 85.4±15 g vs. from 124.8±40.5 to 83.1±24.8 g; PT=0.04), and a statistically significant difference between EXMIS and NOMIS patients concerning the interaction of factors time and mass reduction (LVMMabs and LVMMindex: PG+T<0.05). The baseline values of both variables were significantly higher in NOMIS patients. LVMM/EDVindex significantly decreased in both groups (PT=0.004); the maximum transvalvular pressure gradient significantly decreased from 100.2±33.4 to 33.5±11 mmHg in group EXMIS and from 95.5±29.1 to 27.6±11.1 mmHg in group NOMIS (PT=0.0002), while the EOA increased in both cohorts (from 0.65±0.22 to 1.34±0.40 cm2 vs. from 0.55±0.16 to 1.43±0.41 cm2; PT=0.02). There were no differences found for interaction of the factors time and mass regression (Table 2; Fig. 1).



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  		Fig. 1. LVMMindex, left ventricular myocardial mass index; PT, P value for the factor time; PT+G, P value for interaction of the factors time and group.

 
3.3. Secondary endpoints
Decrease in stroke volume and increase in cardiac output were significantly higher in NOMIS patients (P<0.05). The left ventricular ejection fraction increased by 7.96% in group EXMIS and by 7.63% in group NOMIS (P<0.05). The quality of life variable, NYHA, showed a significant trend in both groups (from 2.97±0.71 to 1.52±0.51 vs. from 2.88±0.61 to 1.33±0.22; P=0.0009); renal function, controlled by the variable creatinine, was at normal levels (Table 2). At the same time, we could not find any further differences between the cohorts concerning the factors time and group. A uniform regression of wall thickness at defined points of left ventricle at systole and diastole emphasized the conception of recovery of concentric left ventricular hypertrophy, although the systolic and diastolic wall thickness only diminished significantly in positions 6 and 7 (Figs. 2 and 3).



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  		Fig. 2. WTsys1, systolic wall thickness at position 1 (anterior, superior); WTsys2, systolic wall thickness at position 2 (anterior, median); WTsys3, systolic wall thickness at position 3 (anterior, inferior); WTsys4, systolic wall thickness at position 4 (apical); WTsys5, systolic wall thickness at position 5 (posterior, inferior); WTsys6, systolic wall thickness at position 6 (posterior); WTsys7, systolic wall thickness at position 7 (posterior and posterolateral). (Solid line), control T0; (semi-interrupted line), control T1; (interrupted line), control T2.

 


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  		Fig. 3. WTdias1, diastolic wall thickness at position 1 (anterior, superior); WTdias2, diastolic wall thickness at position 2 (anterior, median); WTdias3, diastolic wall thickness at position 3 (anterior, inferior); WTdias4, diastolic wall thickness at position 4 (apical); WTdias5, diastolic wall thickness at position 5 (posterior, inferior and diaphragmal); WTdias6, diastolic wall thickness at position 6 (posterior); WTdias7, diastolic wall thickness at position 7 (posterior and posterolateral). (Solid line), control T0; (semi-interrupted line), control T1; (interrupted line), control T2.

 
3.4. Validation of the model
The variables, LVMMabs and cardiac output, were calculated with positive regression coefficients at baseline by stepwise logistic regression; patient BSA, preoperative myocardial perfusion and EOA of the stenotic aortic valve were estimated with negative premises (Table 3). In our exponential model, P was the probability of a minimum LVMMabs regression of 25% from baseline, i.e. normalization of LVMMindex at both controls T1 and T2, and the formula in Eq. (3)

((3))

Using this formula, in 81.82% of all cases, normalization of the indexed left ventricular mass was correctly classified.


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  		Table 3. Logistic regression report

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
Appendix A. Conference...
 References
 
In 1978, Rahimtoola [2] described a valve prosthesis–patient mismatch in a population of patients receiving a caged silastic ball prosthesis for AVR in patients with pure aortic regurgitation, where the average calculated EOA was even 1.7 cm2, but only 0.7–1.6 cm2/m2 indexed for BSA. In this report, the author emphasized an exponential function as the relationship between the mean systolic transprosthetic gradient and valve area. Following the first enthusiasm about biological xenografts in the late 1980s, some outstanding reports [3] were published highlighting the validation and applications of indexed aortic prosthetic valve areas using the continuity equation calculated by Doppler echocardiography. In an in vitro physiologic pulse duplicator system, Dumesnil and Yoganathan studied the exponential relations between mean transprosthetic pressure gradients and indexed EOAs for aortic bioprostheses assuming ‘that the indexed EOA should ideally be no less than 0.9–1.0 cm2/m2’ [4]. In 1996, the same working group concluded that in cases of prosthesis–patient mismatch, the hemodynamic performance was worse and was associated with a higher occurrence of adverse clinical events, including syncopal events, pulmonary problems and angina pectoris [19].

As a matter of fact, on review of the literature, it emerged that similar reports in the field of AVR with mechanical prostheses are very rare. According to our own published findings in patients with a small-sized aortic annulus, we emphatically refer to Fernandez et al., who demonstrated, in a very large series of patients, that VAI and a possible mismatch were not correlated with early and late mortality or morbidity [7,8].

In our present work, VAI occurred as an objective and specific parameter, making the limits of possible valve prosthesis–patient mismatch very clear and reproducible. Statistical analysis appeared to be highly sensitive for implanted valve diameter, geometric orifice area and VAI (Table 1). The intraoperative matching of prostheses’ in vitro measured effective areas and patients’ BSAs appears rather artificial and clearly not reproducible for all valve types. Furthermore, it was proven that the assignation and randomization of patients was distinct and comprehensible. The described study protocol was extremely ambitious for investigators and participating patients concerning the quality and quantity of long-term follow-up, costs and technical efforts.

In comparison with other methods (echocardiography, contrast ventriculography, magnetic resonance imaging and single photon emission computed tomography), the investigation of myocardial mass by EBT warrants the highest standards of interobserver and intraobserver variability, being found to be highly reproducible without being invasive [20,21]. The comparisons between left ventricular mass ex vivo and that calculated from the EBT in vivo were excellent, with the difference in parameters in patients who had more than one EBT within 24 h being 1–2%, and the difference between two observers was approximately 4%.

Our present study on the in vivo performance of modern small-sized aortic valve prostheses demonstrates that changes of maximum transvalvular pressure gradients and EOAs of the tested CarboMedics® prosthesis were clinically acceptable (Table 2). Unexpectedly, the differences between EXMIS and NOMIS patients referring to LVMMabs and LVMMindex for the interaction of the factors time and mass regression were not a consequence of a pathological way of recovery in EXMIS patients. Special attention should be paid to these discrepancies as we do interpret these findings as the fact that myocardial mass baselines were absolutely and relatively higher in NOMIS patients, which explains this statistical significance, as even both groups showed standard values of healthy ‘in- and outdoor’ probationers at controls T1 and T2 (Table 2; Fig. 1).

Jin et al. [22] recently reported on a number of patient-related factors that also influence LV mass regression and remodelling based on long-term follow-up data after AVR with a stentless xenograft. Actually, the overall regression of LVMMindex measured by echocardiography was found to be from 220±105 pre-AVR to 140±60 g/m2 at 24 months-control. These left ventricular masses appear to be rather high in relation to our results. Indeed, it has been published that the margin of error for a 95% CI in small cohorts is up to 60 g when myocardial masses are assessed by echocardiography [18].

Del Rizzo et al. [23] described regressions of indexed left ventricular myocardial mass postoperatively from 101.5±34.3 to 73.7±23.4 g/m2 in 19 mm and from 118.8±47.5 to 97.5±47.6 g/m2 in 21 mm stentless xenografts (at 3 years). Although these data do confirm our approach, it must be basically noted that this study also differed from our concept in ‘phase I’ regarding the methods (echocardiographic assessment) and choice of prosthesis.

In addition, the outcomes of secondary endpoints seem to prove a uniform regression of wall thickness at defined points of the left ventricle at systole and diastole (Figs. 2 and 3). In combination with an improvement of myocardial perfusion, this fact should evolve in a greater decrease of left ventricular systolic wall stress with consecutive regression of cellular hypertrophy and interstitial fibrosis. We stated that major changes in the left ventricular mass index and loading volumes occurred within the very first 4 months after operation, coming up to a steady state. In fact, this was also described for AVR with stentless xenograft prostheses by the above-mentioned authors [22,23].

The most notable finding from the present analysis is that, although LVMMabs and cardiac output were significant positive predictors for a normalization of indexed LVMM, the factors prosthesis diameter, geometric orifice area of the implanted device and VAI did not play any role in the developed statistical models. Our present final transformation form is an attempt to find a mathematical formula for the prediction of ‘good’ and ‘bad’ patients, i.e. to determine the patients who will have a left ventricular mass regression of at least 25% and those who will not. Several computed models were clearly oversized and were interpreted as descriptions of study data. As it can not be expected to achieve a correct classification of more than 90% for future patients, only significant variables were included with a 10% ‘cut-off’. We did not only analyze the rate of left ventricular mass regression at long-term follow-up, but also, differences in these rates at determined controls. However, using this model, we are definitively not able to predict the dimension of left ventricular mass regression for any given patient.

Certain limitations of the present study have to be mentioned. There is a small group of patients under observation, although statistical validation of the achieved results appeared to be accurate. Another fact is the choice of only one valve type. This report presents the ‘phase I’ results of a prospective, randomized and long-term clinical trial, which was started in 1996. Phase II – with a definitive study cohort of about 150 patients – is under investigation and will be finished by June 2001. In these parts of our clinical trial, we will report on changes in left ventricular architecture after AVR with different types of valves. Furthermore, the regression coefficients of present risk factors in the training set population will serve for calculation of predicted primary study endpoints of the overall test cohort. In this case, the predicted variables of left ventricular mass regression and hemodynamics will be compared for deviation from the observed results across the entire risk spectrum.

It appears more conceivable that patient–prosthesis mismatch is negligible with modern small-sized bileaflet aortic valve prostheses. Recent studies demonstrating similar findings after AVR in patients with different matching between implanted prosthesis and BSA may be explained by our results [9,14,23].

Summing up, it may be concluded that in the presence of a SAR careful evaluation of influencing factors – patient's age and clinical status, available types of prostheses and familiarity of surgical techniques – must serve as a basis for decision making. The small-sized aortic prostheses of the present generation seem to allow both acceptable hemodynamics and the recovery of left ventricular hypertrophy in annuli that may have traditionally been a case for aortic root enlargement. Although, the conception of implanting these prostheses regardless of the patient's BSA might appear very controversial at first sight, we emphasize our results and their notable clinical relevance.


   Acknowledgments
 
By intention, the study was independent from extramural financial funds as none of the authors or patients received any financial compensation for their participation. This clinical trial was approved by the ‘Ethics Committee Institutional Review Board of the General and University Hospital and Karl Franzens University of Graz‘ under reference number 07-070/A ex 96/97. The authors would like to thank Mr Thomas Röding (A. Duschek GmbH, Vienna, Austria) for his assistance in providing us technical data of the CarboMedics® prosthetic heart valve.


   Footnotes
 
Presented at the 14th Annual Meeting of the European Association for Cardio-thoracic Surgery, Frankfurt, Germany, October 7–11, 2000.


   Appendix A. Conference discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
References
 
Dr G. Dellgren (Stockholm, Sweden): I am somewhat concerned about the results in this study and the studies alike for the following reason. The degree of left ventricular hypertrophy in aortic stenosis, as well as the degree of regression postoperatively, have been found to be related to genetic factors. The aortic stenosis is also likely to be just the stimulus in this process and not the determinant of the degree of left ventricular hypertrophy. Supporting evidence for this is, first, shown in several studies, the degree of left ventricular hypertrophy is not related to the degree or severity of aortic stenosis measured as the area or the transvalvular gradient.

Second, the left ventricular hypertrophy or phenotype in aortic stenosis has been found to be related to the genotype of the ACE gene and also likely to other genes. Since we know nothing about the distribution of these genotypes in this study, it is rather unsafe to draw these conclusions. Therefore, in my opinion, the whole discussion about valve prosthesis–patient mismatch and small diameter prosthesis has become simplified and reduced to just a mechanical issue. The degree of left ventricular hypertrophy, as well as the regression of left ventricular hypertrophy, are regulated genetically and need to be further explored and also integrated into these studies before we can draw any safe conclusions.

Dr Knez: First of all, the presented data are results of the very first phase of a long-term clinical study. This means that the second and third phases of our investigation will involve several types of mechanical and biological valves and will hopefully be published within the next 6 months.

Secondly, what could be misunderstood is the fact that we are not telling you exactly the amount of regression of left ventricular myocardial mass. Basically, we tried to explain that under certain circumstances, our method provides a very specific and sensitive prediction for a patient with critical aortic stenosis undergoing prosthetic valve replacement to have a ‘good’ or a ‘bad’ outcome, i.e. to have a regression of indexed left ventricular myocardial mass of at least 25%, which means a normalization of LV-hypertrophy.

Although the first phase enrolled 60 patients – which might appear a small number – the statistical analysis appeared very accurate.

We have to admit that we were surprised about the fact that antihypertensive drugs, i.e. essential hypertension, might play a big role in the predictive formula and we concluded to focus our attention on ACE polymorphism in our further investigations.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
 References
 

  1. Anderson R.H., Lal M., Ho S.Y. Anatomy of the aortic root with particular emphasis on options for its surgical enlargement. J Heart Valve Dis 1996;5(Suppl 3):249-257.
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  3. Dumesnil J.G., Honos G.N., Lemieux M., Beauchemin J. Validation and application of indexed aortic prosthetic valve areas calculated by Doppler echocardiography. J Am Coll Cardiol 1990;16:637-643.[Abstract]
  4. Dumesnil J.G., Yoganathan A.P. Valve prosthesis hemodynamics and the problem of high transprosthetic pressure gradients. Eur J Cardio-thorac Surg 1992;6(Suppl 1):34-38.
  5. Morris J.J., Schaff H.V., Mullary C.J. Determinants of survival and recovery of left ventricular function after aortic valve replacement. Ann Thorac Surg 1993;56:22-30.[Abstract]
  6. Pupello D.F., Blank R.H., Bessone L.N., Harrison E.S., Sbar S. Surgical management of the small aortic annulus. Chest 1978;74(2):163-166.[Abstract/Free Full Text]
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  8. Fernandez J., Chen Ch., Laub G.W., Anderson W.A., Brdlik O.B., Murphy M.M., McGrath L.B. Predictive value of prosthetic valve area index for early and late clinical results after valve replacement with the St. Jude medical valve prosthesis. Circulation 1996;94(Suppl 2):109-112.
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