- Email: [email protected]
Effect of statins on the progression of bioprosthetic aortic valve degeneration
with acute (nonhemorrhagic) stroke had a lower prevalence of AF, despite a greater prevalence of diabetes and hypertension, than whites. AF was an independent predictor of increased mortality after stroke in our multiethnic population as a whole, but AF appears to be a less prominent factor in stroke among IndoAsians and Afro-Caribbeans than in whites.
1. Sacco RL, Kargman DE, Zamanillo MC. Race-ethnic differences in stroke risk
factors among hospitalized patients with cerebral infarction: the Northern Manhattan Stroke Study. Neurology 1995;45:659 –663. 2. Hajat C, Dundas R, Stewart JA, Lawrence E, Rudd AG, Howard R, Wolfe CD. Cerebrovascular risk factors and stroke subtypes: differences between ethnic groups. Stroke 2001;32:37–42. 3. Bornstein NM, Aronovich BD, Karepov VG, Gur AY, Treves TA, Oved M, Korczyn AD. The Tel Aviv Stroke Registry: 3600 consecutive patients. Stroke 1996;27:1770 –1773.
Effect of Statins on the Progression of Bioprosthetic Aortic Valve Degeneration Francesco Antonini-Canterin, MD, Alfredo Zuppiroli, MD, Bogdan A. Popescu, MD, Gianluca Granata, MD, Eugenio Cervesato, PhD, Rita Piazza, MD, Daniela Pavan, MD, and Gian Luigi Nicolosi, MD To date, there is no proved medical therapy able to significantly reduce the degenerative process of biologic prosthetic aortic valves. It has recently been suggested that statins may reduce the progression of native aortic valve stenosis. We examined the effect of statin treatment on bioprosthetic aortic valve degeneration and found a beneficial effect of statins in slowing bioprosthetic degeneration. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:1479 –1482)
systematic retrospective analysis of our adult echocardiography computerized database was A performed. All patients with a bioprosthetic aortic valve who were studied between 1988 and 2002 were screened for inclusion in the study. Patients were required to have at least 2 complete transthoracic echocardiographic examinations ⬎6 months apart. Demographic, clinical, and laboratory data were obtained by review of patients’ medical records and by interviews. Use of a statin was identified and information regarding type of drug, dose, and duration of treatment was obtained.1–3 Treatment with a lipidlowering agent was done at the discretion of the patient’s physician. One hundred sixty-seven patients (97 men and 70 women, mean ⫾ SD age 71 ⫾ 9 years at the first examination) were identified who met study criteria. Mean follow-up duration was 46 ⫾ 38 months (range 6 to 165). Among them, 22 (13.2%) received statins throughout follow-up (11 men, mean ⫾ SD age 73 ⫾ 6 years). ••• From Unita` Operativa di Cardiologia, A.R.C., Azienda Ospedaliera S. Maria degli Angeli, Pordenone, Italy; Azienda Ospedaliera Careggi, Firenze, Italy; and “Prof. Dr. C.C. Iliescu” Institute of Cardiovascular Diseases, Bucharest, Romania. Dr. Popescu was supported by a Research Fellowship of the Association for Research in Cardiology, Pordenone, Italy. Dr. Antonini-Canterin’s address is: Unita` Operativa di Cardiologia, A.R.C., Azienda Ospedaliera S. Maria degli Angeli Via Montereale 24, 33170 Pordenone, Italy. E-mail: cardiologia@ aopn.fvg.it. Manuscript received July 16, 2003; revised manuscript received and accepted August 22, 2003. ©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 December 15, 2003
These clinical data were recorded: clinical status; year of aortic bioprosthesis implantation and time interval to the moment of the first echocardiographic examination; history of hypertension, hypercholesterolemia, diabetes mellitus, current smoking, and endstage renal disease requiring dialysis. Also, prior evidence of coronary artery disease (history of myocardial infarction, coronary angioplasty, coronary artery bypass grafting, or coronary artery disease by coronary angiography [epicardial coronary stenosis ⬎50%]) was recorded. The major clinical events were defined as death or repeat aortic valve operation for structural valve deterioration. All echocardiographic data were acquired and interpreted by an experienced staff cardiologist. Interpretation of echocardiographic studies was conducted without knowledge of the present study. Comprehensive examinations were performed on all study patients, including 2-dimensional, pulsed- and continuous-wave, and color Doppler echocardiography. Commercially available echocardiographic systems equipped with 2.5- to 3.5-MHz phased-array transducers were used. Standard views and techniques were used according to the guidelines of the American Society of Echocardiography.4 Peak and mean aortic valve flow velocities were determined by continuouswave Doppler, systematically sampling the flow from different windows, and selecting the highest profile envelope. The maximal instantaneous gradient and the mean gradient across the aortic valve were derived from aortic continuous-wave Doppler velocities by the simplified Bernoulli equation. Gradients were obtained by averaging the values over ⬎3 consecutive beats in sinus rhythm and 5 consecutive beats in atrial fibrillation. Prosthetic effective orifice area was calculated by the continuity equation method. Because we aimed at analyzing changes with time rather than absolute values of effective orifice area, the labeled size of the prosthesis was used instead of the left ventricular outflow tract diameter in the continuity equation, as previously described,5 to ensure less variability in the serial analysis. Indexed effective orifice area was calculated by dividing effective orifice area 0002-9149/03/$–see front matter doi:10.1016/j.amjcard.2003.08.066
1479
categoric data as percentages. For comparing analysis between patients treated and not treated with statins, Statin Therapy Student’s t test was used for continuous variables and the chi-square test Variables ⫹ (n ⫽ 22) 0 (n ⫽ 145) p Value for dichotomous variables. A p value Age (yrs) 73 ⫾ 6 71 ⫾ 9 0.27 ⬍0.05 was considered significant. Men/women 11/11 86/59 0.55 Statistical analysis was performed Follow-up duration (mo) 44 ⫾ 35 46 ⫾ 38 0.76 Prosthetic size (mm) 23 ⫾ 2 23 ⫾ 2 0.92 using SPSS for Windows, version Baseline peak velocity (m/s) 2.57 ⫾ 0.35 2.52 ⫾ 0.48 0.68 11.5. (SPSS Inc., Chicago, Illinois). Baseline mean gradient (mm Hg) 16 ⫾ 5 16 ⫾ 6 0.77 Patients’ clinical characteristics 1.67 ⫾ 0.24 1.78 ⫾ 0.41 0.21 Baseline effective orifice area (cm2) are listed in Table 1. There were only Indexed effective orifice area (cm2/m2) 0.97 ⫾ 0.17 1.02 ⫾ 0.25 0.38 Baseline degree of aortic regurgitation (mean) 0.59 ⫾ 0.52 0.51 ⫾ 0.55 0.54 3 current smokers and only 1 patient Left ventricular ejection fraction (%) 56 ⫾ 11 56 ⫾ 10 0.92 with end-stage renal disease requirSystemic hypertension 13 (59%) 74 (51%) 0.62 ing dialysis in the entire study group. Diabetes mellitus 4 (18%) 35 (24%) 0.64 Creatinine values at baseline were Hypercholesterolemia (⬎220 mg/dl) 21 (95%) 19 (13%) ⬍0.001 available in 20 of the statin-treated Proven coronary artery disease 17 (77%) 41 (28%) ⬍0.001 Associated coronary bypass 15 (68%) 26 (18%) ⬍0.001 patients (91%) and in 119 of the nonTime from surgery to first echo (yrs) 0.6 ⫾ 0.9 0.8 ⫾ 2 0.63 treated patients (82%), and the mean Porcine bioprosthetic valves 19 (86%) 119 (82%) 0.62 value was not different between the 2 Pericardial bioprosthetic valves 3 (14%) 26 (18%) 0.62 groups (1.28 ⫾ 0.49 and 1.24 ⫾ 0.33 Stentless valves 2 (9%) 19 (13%) 0.59 mg/dl, respectively, p ⫽ 0.64). As expected, more patients in the statin group had documented hypercholesterolemia, proven coronary artery TABLE 2 Changes in Echocardiographic Data and Major Clinical Events During Follow-up disease, or had associated coronary artery bypass grafting at the time of Statin Therapy aortic valve replacement. Three difVariables ⫹ (n ⫽ 22) 0 (n ⫽ 145) p Value ferent statins were administered to the statin group. The agents used, the Rate of increase of peak velocity 0.038 ⫾ 0.074 0.140 ⫾ 0.228 ⬍0.001 (m/s/yr) number of patients, and the mean Rate of increase of mean gradient 0.54 ⫾ 1.03 2.47 ⫾ 4.31 ⬍0.001 daily dosage (⫾ SD) were simvasta(mm Hg/yr) tin (11 patients, 11 ⫾ 5 mg), prava0.031 ⫾ 0.052 0.100 ⫾ 0.150 ⬍0.001 Rate of decrease of effective statin (7 patients, 19 ⫾ 4 mg), and orifice area (cm2/yr) Rate of decrease of indexed 0.019 ⫾ 0.031 0.056 ⫾ 0.086 ⬍0.001 atorvastatin (4 patients, 14 ⫾ 5 mg). effective orifice area No significant adverse effects of sta2 2 (cm /m /yr) tin treatment were recorded during Worsening of aortic regurgitation 2/22 (9.1%) 48/145 (33.1%) 0.022 follow-up. (ⱖ1/3 degrees) Follow-up echocardiographic data Combined parameter of 2/22 (9.1%) 63/145 (43.4%) 0.002 prosthetic degeneration and major clinical events are listed in progression* Table 2. There were 25 deaths and 3 Major clinical events 3/22 (14%) 28/145 (19%) 0.73 repeat aortic operations for biopros(death/reoperation for thetic degeneration in the group taking degeneration) no statins (19%) compared with 3 *Defined as the existence of either an annual rate of increase in peak prosthetic velocity of ⱖ0.3 deaths in the group taking statins m/s/yr or worsening of aortic regurgitation of ⱖ1/3 degrees. (14%, p ⫽ 0.73). No episodes of prosthetic valve endocarditis were encountered. A combined parameter of prosby body surface area. Aortic regurgitation was graded thetic degeneration progression, defined as the existence semiquantitatively by color Doppler echocardiogra- of either an annual rate of increase in peak velocity of phy.6 The echocardiographic Doppler data of the last ⱖ0.3 m/s/year7 or worsening of aortic regurgitation with examination were compared with the initial data. In ⱖ1/3 degrees was more frequently found in the group the case of repeat operation, the last echocardio- without statins. The odds ratio of prosthetic degeneration graphic examination before surgery was considered. progression (defined by this parameter) with statin treatProgression of bioprosthetic aortic valve degenera- ment was 0.13 (95% confidence interval 0.03 to 0.58). tion was assessed by measuring the changes in peak The odds ratio of worsening aortic regurgitation with and mean prosthetic gradients, effective orifice statin treatment was 0.20 (95% confidence interval: 0.04 area, and indexed effective orifice area. Rates were to 0.90). The overall annual rate of progression of peak calculated on an annualized basis (by dividing the prosthetic velocity was similar between porcine and periabsolute change by the time interval between ex- cardial valves (0.13 ⫾ 0.23 vs 0.09 ⫾ 0.13 m/s/year, p ⫽ aminations). 0.31) and between stented and stentless valves (0.13 ⫾ Continuous data are expressed as mean ⫾ SD and 0.20 vs 0.13 ⫾ 0.30 m/s/year, p ⫽ 0.85). TABLE 1 Baseline Clinical and Echocardiographic Characteristics of the Two Groups
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that statin therapy may slow the progression of mild or moderate aortic stenosis in human native valves.1–3 Clinical Factors Present Absent p Value Two other studies10,11 using electron-beam computed tomography Age ⱖ70 yrs 0.11 ⫾ 0.21 0.15 ⫾ 0.24 0.27 Diabetes mellitus 0.17 ⫾ 0.31 0.12 ⫾ 0.21 0.25 showed a significantly decreased rate Hypertension 0.12 ⫾ 0.26 0.14 ⫾ 0.21 0.59 in aortic valve calcium accumulation Coronary artery disease 0.12 ⫾ 0.22 0.13 ⫾ 0.22 0.81 in patients treated with statins comHypercholesterolemia (⬎220 mg/dl) 0.15 ⫾ 0.32 0.12 ⫾ 0.20 0.47 pared with controls. These results 0.12 ⫾ 0.17 0.13 ⫾ 0.27 0.87 Body mass index ⱖ25 (kg/m2) Statin use 0.04 ⫾ 0.07 0.14 ⫾ 0.23 ⬍0.001 are remarkably similar in suggesting that statin treatment could slow the rate of progression of native aortic valve stenosis. The possible mechanism of statin treatment benefit in TABLE 4 Influence of Clinical Factors on Annual Rate of Change in Prosthetic slowing aortic stenosis progression is Indexed Effective Orifice Area (cm2/m2/yr) not clear. The correlation between Clinical Factors Present Absent p Value lipid levels and aortic stenosis proAge ⱖ70 yrs ⫺0.050 ⫾ 0.078 ⫺0.054 ⫾ 0.091 0.79 gression is very controversial. Two Diabetes mellitus ⫺0.045 ⫾ 0.061 ⫺0.056 ⫾ 0.090 0.56 studies1,10 found a significant corHypertension ⫺0.050 ⫾ 0.075 ⫺0.058 ⫾ 0.094 0.58 relation, whereas other studies2,3 Coronary artery disease ⫺0.056 ⫾ 0.091 ⫺0.047 ⫾ 0.073 0.52 showed a lack of correlation beHypercholesterolemia (⬎220 mg/dl) ⫺0.051 ⫾ 0.088 ⫺0.054 ⫾ 0.084 0.85 tween lipid levels and aortic steno⫺0.058 ⫾ 0.083 ⫺0.044 ⫾ 0.080 0.28 Body mass index ⱖ25 (kg/m2) Statin use ⫺0.019 ⫾ 0.031 ⫺0.056 ⫾ 0.086 ⬍0.001 sis progression. In the present study, statin-treated patients had a reduced progression of bioprosThe influence of several clinical factors on biopros- thetic degeneration despite higher cholesterol levthetic aortic valve degeneration was also evaluated. els. This is concordant with results obtained in Results are listed in Tables 3 and 4. The only factor native aortic stenosis,3 and suggests that the beneassociated with progression of bioprosthetic aortic ficial effect of statins in slowing bioprosthetic valve valve degeneration was statin treatment; patients degeneration is not due to their lipid-lowering eftreated with statins had significantly lower rates of fects, but rather to their pleiotropic effects over and bioprosthetic degeneration, as assessed by different above lipid lowering, including anti-inflammatory parameters. Because in the univariate analyses both effects,12 with reduction of C-reactive protein indethe rate of increase in peak velocity and the rate of pendent of lipid changes.13 decrease in indexed effective orifice area were influOur study provides evidence that statin treatment is enced significantly only by statin treatment, while all associated with significantly less bioprosthetic aortic other variables had no effect (p values ⬎0.20 for all valve degeneration. This finding could influence the the other variables), a multivariate analysis was not type of aortic valve prosthesis chosen in patients reperformed. quiring aortic valve replacement, and could therefore ••• contribute to the clinical decision-making in these In our study, although all echocardiographic pa- patients. rameters of bioprosthetic aortic valve function were similar at baseline in the 2 groups, the annual rates of change of all these parameters were significantly re- 1. Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older duced in the statin group. persons. Am J Cardiol 2001;88:693–695. At present, all porcine valves have similar rates of 2. Novaro GM, Tiong IY, Pearce GL, Lauer MS, Sprecher DL, Griffin BP. Effect 8 structural valve degeneration. In our study, more of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of patients had a porcine aortic valve than a pericardial calcific aortic stenosis. Circulation 2001;104:2205–2209. Bellamy MF, Pellikka PA, Klarich KW, Tajik AJ, Enriquez-Sarano M. Assovalve, and there were more stented than stentless 3. ciation of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase invalves. However, there were no differences regarding hibitor treatment, and progression of aortic stenosis in the community. J Am Coll the proportion of porcine versus pericardial prosthe- Cardiol 2002;40:1723–1730. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, ses, or the proportion of stented versus stentless valves 4. Gutgesell H, Reichek N, Sahn D, Schnittger I, et al. Recommendations for between the 2 groups (Table 1). Several studies, con- quantification of the left ventricle by two-dimensional echocardiography. J Am ducted both in animal models and in humans, ad- Soc Echocardiogr 1989;2:358 –367. 5. Chafizadeh ER, Zoghbi WA. Doppler echocardiographic assessment of the St. dressed the question on the role of statin treatment in Jude Medical prosthetic valve in the aortic position using the continuity equation. the progression of aortic valve stenosis. In a choles- Circulation 1991;83:213–223. terol-fed rabbit model, hypercholesterolemia was 6. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insuffiby Doppler color flow mapping. J Am Coll Cardiol 1987;9:952–959. proved to produce atherosclerotic lesions in the aortic ciency 7. Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, Healy NL, Kraft CD, valve, and atorvastatin was proved to influence the Miyake-Hull CY, Schwaegler RG. Prospective study of asymptomatic valvular pathogenic mechanism, reducing the extent of athero- aortic stenosis: clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95:2262–2270. sclerotic changes in the aortic valve.9 Over the last 8. Grunkemeier GL, Bodnar E. Comparative assessment of bioprosthesis durayears, a number of nonrandomized studies reported bility in the aortic position. J Heart Valve Dis 1995;4:49 –55. TABLE 3 Influence of Clinical Factors on Annual Rate of Increase in Peak Prosthetic Velocity (m/s/yr)
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9. Rajamannan NM, Subramaniam M, Springett M, Sebo TC, Niekrasz M, McConnell JP, Singh RJ, Stone NJ, Bonow RO, Spelsberg TC. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation 2002;105:2660 –2665. 10. Pohle K, Maffert R, Ropers D, Moshage W, Stilianakis N, Daniel WG, Achenbach S. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001; 104:1927–1932.
11. Shavelle DM, Takasu J, Budoff MJ, Mao S, Zhao XQ, O’Brien KD. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet 2002;359:1125– 1126. 12. Farmer JA. Pleiotropic effects of statins. Curr Atheroscler Rep 2000;2:208 – 217. 13. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation 1999; 100:230 –235.
Intracardiac Echocardiography During Transcatheter Interventions for Congenital Heart Disease John F. Rhodes, Jr., MD, Athar M. Qureshi, MD, Tamar J. Preminger, MD, E. Murat Tuzcu, MD, Ivan P. Casserly, MD, Kent W. Dauterman, MD, Lourdes R. Prieto, MD, C. Igor Mesia, MD, Geoffrey K. Lane, MBBS, Penny A. Radvansky, RN, and Larry A. Latson, MD Although transesophageal echocardiography is often used for guidance during transcatheter interventions, few data exist regarding the use of the newer modality of intracardiac echocardiography. This brief report summarizes our single center experience using intracardiac echocardiographic guidance during transcatheter interventional procedures for congenital heart disease. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:1482–1484)
catheterization for structural heart disease has changed dramatically over the past deIcadenterventional as transcatheter closure devices for septal defects and patent foramen ovale have become partially or completely approved by the Food and Drug Administsration (FDA). Many of these interventions are typically guided by both fluoroscopic and echocardiographic imaging. The standard ultrasound technique for guidance during transcatheter interventions for congenital heart disease has been transesophageal echocardiography (TEE).1 Echocardiography specialists, even in the catheterization laboratory, usually perform TEE.2 However, recent advances have made intracardiac ultrasound imaging by the invasive cardiologist a viable alternative. We report data regarding the efficacy and safety of intracardiac echocardiography (ICE) during interventional catheterization procedures. •••
Data were retrospectively collected for all patients who underwent a cardiac catheterization procedure using ICE between May 2001 and February 2003. All procedures were performed while patients were under conscious sedation. A standard 11Fr venous sheath was placed percutaneously. An AcuNav (Acuson) From the Departments of Cardiovascular Medicine and Pediatric and Congenital Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Dr. Rhodes’ address is: Pediatric Cardiovascular Program, Duke University Medical Center, DUMC-3090, Durham, North Carolina 27710. E-mail: [email protected]. Manuscript received March 13, 2003; revised manuscript received and accepted August 21, 2003.
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©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 December 15, 2003
10Fr multifrequency, single-plane ICE catheter was connected to a Sequoia or Cypress ultrasound console (Siemens Medical Solutions, Mountain View, California). The catheter was pretested in a saline solution to confirm imaging before placement in the patient and then advanced through the sheath with the operator’s fingers close to the tip to avoid damaging the ultrasound crystals. We preferred to advance the catheter under fluoroscopic guidance to the right atrium to ensure safe passage through the vasculature. Careful steering of the catheter tip was critical along the common femoral and common iliac vein, and in the inferior vena cava at the level of the hepatic veins. If there was difficulty advancing the ICE catheter, a long (30-cm) venous sheath can be used to overcome difficulty in getting through the common femoral and common iliac vein. After advancing the catheter in the neutral (unlocked) position to the high right atrium, it was deflected posterior and rightward (patient’s right and control knob left) and locked in a position slightly to the right of the patient’s spine. The catheter was then either advanced superior-inferior by advancing/ withdrawing the catheter or anterior-posterior by rotating counterclockwise/clockwise to change the image. Only minor manipulations were made to avoid overtorquing the catheter and thus loss of position once the catheter was released. •••
During the study period, 203 patients (median age 47 years, range 9 to 85) underwent a transcatheter intervention with ICE guidance. During each catheterization, the invasive physician performed ICE imaging as well as transcatheter intervention. In most of our patients (n ⫽ 191), the standard transfemoral approach with a venous sheath in bilateral veins was used. This approach was used in 7 patients despite the presence of an inferior vena cava filter. The venous sheath for ICE was placed in the same femoral vein as the delivery sheath for 9 patients, and for 2 patients with femoral venous occlusion, the venous sheath for the ICE catheter was placed in the internal jugular vein. Also, for 1 patient with an interrupted inferior 0002-9149/03/$–see front matter doi:10.1016/j.amjcard.2003.08.067
1. Sacco RL, Kargman DE, Zamanillo MC. Race-ethnic differences in stroke risk
factors among hospitalized patients with cerebral infarction: the Northern Manhattan Stroke Study. Neurology 1995;45:659 –663. 2. Hajat C, Dundas R, Stewart JA, Lawrence E, Rudd AG, Howard R, Wolfe CD. Cerebrovascular risk factors and stroke subtypes: differences between ethnic groups. Stroke 2001;32:37–42. 3. Bornstein NM, Aronovich BD, Karepov VG, Gur AY, Treves TA, Oved M, Korczyn AD. The Tel Aviv Stroke Registry: 3600 consecutive patients. Stroke 1996;27:1770 –1773.
Effect of Statins on the Progression of Bioprosthetic Aortic Valve Degeneration Francesco Antonini-Canterin, MD, Alfredo Zuppiroli, MD, Bogdan A. Popescu, MD, Gianluca Granata, MD, Eugenio Cervesato, PhD, Rita Piazza, MD, Daniela Pavan, MD, and Gian Luigi Nicolosi, MD To date, there is no proved medical therapy able to significantly reduce the degenerative process of biologic prosthetic aortic valves. It has recently been suggested that statins may reduce the progression of native aortic valve stenosis. We examined the effect of statin treatment on bioprosthetic aortic valve degeneration and found a beneficial effect of statins in slowing bioprosthetic degeneration. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:1479 –1482)
systematic retrospective analysis of our adult echocardiography computerized database was A performed. All patients with a bioprosthetic aortic valve who were studied between 1988 and 2002 were screened for inclusion in the study. Patients were required to have at least 2 complete transthoracic echocardiographic examinations ⬎6 months apart. Demographic, clinical, and laboratory data were obtained by review of patients’ medical records and by interviews. Use of a statin was identified and information regarding type of drug, dose, and duration of treatment was obtained.1–3 Treatment with a lipidlowering agent was done at the discretion of the patient’s physician. One hundred sixty-seven patients (97 men and 70 women, mean ⫾ SD age 71 ⫾ 9 years at the first examination) were identified who met study criteria. Mean follow-up duration was 46 ⫾ 38 months (range 6 to 165). Among them, 22 (13.2%) received statins throughout follow-up (11 men, mean ⫾ SD age 73 ⫾ 6 years). ••• From Unita` Operativa di Cardiologia, A.R.C., Azienda Ospedaliera S. Maria degli Angeli, Pordenone, Italy; Azienda Ospedaliera Careggi, Firenze, Italy; and “Prof. Dr. C.C. Iliescu” Institute of Cardiovascular Diseases, Bucharest, Romania. Dr. Popescu was supported by a Research Fellowship of the Association for Research in Cardiology, Pordenone, Italy. Dr. Antonini-Canterin’s address is: Unita` Operativa di Cardiologia, A.R.C., Azienda Ospedaliera S. Maria degli Angeli Via Montereale 24, 33170 Pordenone, Italy. E-mail: cardiologia@ aopn.fvg.it. Manuscript received July 16, 2003; revised manuscript received and accepted August 22, 2003. ©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 December 15, 2003
These clinical data were recorded: clinical status; year of aortic bioprosthesis implantation and time interval to the moment of the first echocardiographic examination; history of hypertension, hypercholesterolemia, diabetes mellitus, current smoking, and endstage renal disease requiring dialysis. Also, prior evidence of coronary artery disease (history of myocardial infarction, coronary angioplasty, coronary artery bypass grafting, or coronary artery disease by coronary angiography [epicardial coronary stenosis ⬎50%]) was recorded. The major clinical events were defined as death or repeat aortic valve operation for structural valve deterioration. All echocardiographic data were acquired and interpreted by an experienced staff cardiologist. Interpretation of echocardiographic studies was conducted without knowledge of the present study. Comprehensive examinations were performed on all study patients, including 2-dimensional, pulsed- and continuous-wave, and color Doppler echocardiography. Commercially available echocardiographic systems equipped with 2.5- to 3.5-MHz phased-array transducers were used. Standard views and techniques were used according to the guidelines of the American Society of Echocardiography.4 Peak and mean aortic valve flow velocities were determined by continuouswave Doppler, systematically sampling the flow from different windows, and selecting the highest profile envelope. The maximal instantaneous gradient and the mean gradient across the aortic valve were derived from aortic continuous-wave Doppler velocities by the simplified Bernoulli equation. Gradients were obtained by averaging the values over ⬎3 consecutive beats in sinus rhythm and 5 consecutive beats in atrial fibrillation. Prosthetic effective orifice area was calculated by the continuity equation method. Because we aimed at analyzing changes with time rather than absolute values of effective orifice area, the labeled size of the prosthesis was used instead of the left ventricular outflow tract diameter in the continuity equation, as previously described,5 to ensure less variability in the serial analysis. Indexed effective orifice area was calculated by dividing effective orifice area 0002-9149/03/$–see front matter doi:10.1016/j.amjcard.2003.08.066
1479
categoric data as percentages. For comparing analysis between patients treated and not treated with statins, Statin Therapy Student’s t test was used for continuous variables and the chi-square test Variables ⫹ (n ⫽ 22) 0 (n ⫽ 145) p Value for dichotomous variables. A p value Age (yrs) 73 ⫾ 6 71 ⫾ 9 0.27 ⬍0.05 was considered significant. Men/women 11/11 86/59 0.55 Statistical analysis was performed Follow-up duration (mo) 44 ⫾ 35 46 ⫾ 38 0.76 Prosthetic size (mm) 23 ⫾ 2 23 ⫾ 2 0.92 using SPSS for Windows, version Baseline peak velocity (m/s) 2.57 ⫾ 0.35 2.52 ⫾ 0.48 0.68 11.5. (SPSS Inc., Chicago, Illinois). Baseline mean gradient (mm Hg) 16 ⫾ 5 16 ⫾ 6 0.77 Patients’ clinical characteristics 1.67 ⫾ 0.24 1.78 ⫾ 0.41 0.21 Baseline effective orifice area (cm2) are listed in Table 1. There were only Indexed effective orifice area (cm2/m2) 0.97 ⫾ 0.17 1.02 ⫾ 0.25 0.38 Baseline degree of aortic regurgitation (mean) 0.59 ⫾ 0.52 0.51 ⫾ 0.55 0.54 3 current smokers and only 1 patient Left ventricular ejection fraction (%) 56 ⫾ 11 56 ⫾ 10 0.92 with end-stage renal disease requirSystemic hypertension 13 (59%) 74 (51%) 0.62 ing dialysis in the entire study group. Diabetes mellitus 4 (18%) 35 (24%) 0.64 Creatinine values at baseline were Hypercholesterolemia (⬎220 mg/dl) 21 (95%) 19 (13%) ⬍0.001 available in 20 of the statin-treated Proven coronary artery disease 17 (77%) 41 (28%) ⬍0.001 Associated coronary bypass 15 (68%) 26 (18%) ⬍0.001 patients (91%) and in 119 of the nonTime from surgery to first echo (yrs) 0.6 ⫾ 0.9 0.8 ⫾ 2 0.63 treated patients (82%), and the mean Porcine bioprosthetic valves 19 (86%) 119 (82%) 0.62 value was not different between the 2 Pericardial bioprosthetic valves 3 (14%) 26 (18%) 0.62 groups (1.28 ⫾ 0.49 and 1.24 ⫾ 0.33 Stentless valves 2 (9%) 19 (13%) 0.59 mg/dl, respectively, p ⫽ 0.64). As expected, more patients in the statin group had documented hypercholesterolemia, proven coronary artery TABLE 2 Changes in Echocardiographic Data and Major Clinical Events During Follow-up disease, or had associated coronary artery bypass grafting at the time of Statin Therapy aortic valve replacement. Three difVariables ⫹ (n ⫽ 22) 0 (n ⫽ 145) p Value ferent statins were administered to the statin group. The agents used, the Rate of increase of peak velocity 0.038 ⫾ 0.074 0.140 ⫾ 0.228 ⬍0.001 (m/s/yr) number of patients, and the mean Rate of increase of mean gradient 0.54 ⫾ 1.03 2.47 ⫾ 4.31 ⬍0.001 daily dosage (⫾ SD) were simvasta(mm Hg/yr) tin (11 patients, 11 ⫾ 5 mg), prava0.031 ⫾ 0.052 0.100 ⫾ 0.150 ⬍0.001 Rate of decrease of effective statin (7 patients, 19 ⫾ 4 mg), and orifice area (cm2/yr) Rate of decrease of indexed 0.019 ⫾ 0.031 0.056 ⫾ 0.086 ⬍0.001 atorvastatin (4 patients, 14 ⫾ 5 mg). effective orifice area No significant adverse effects of sta2 2 (cm /m /yr) tin treatment were recorded during Worsening of aortic regurgitation 2/22 (9.1%) 48/145 (33.1%) 0.022 follow-up. (ⱖ1/3 degrees) Follow-up echocardiographic data Combined parameter of 2/22 (9.1%) 63/145 (43.4%) 0.002 prosthetic degeneration and major clinical events are listed in progression* Table 2. There were 25 deaths and 3 Major clinical events 3/22 (14%) 28/145 (19%) 0.73 repeat aortic operations for biopros(death/reoperation for thetic degeneration in the group taking degeneration) no statins (19%) compared with 3 *Defined as the existence of either an annual rate of increase in peak prosthetic velocity of ⱖ0.3 deaths in the group taking statins m/s/yr or worsening of aortic regurgitation of ⱖ1/3 degrees. (14%, p ⫽ 0.73). No episodes of prosthetic valve endocarditis were encountered. A combined parameter of prosby body surface area. Aortic regurgitation was graded thetic degeneration progression, defined as the existence semiquantitatively by color Doppler echocardiogra- of either an annual rate of increase in peak velocity of phy.6 The echocardiographic Doppler data of the last ⱖ0.3 m/s/year7 or worsening of aortic regurgitation with examination were compared with the initial data. In ⱖ1/3 degrees was more frequently found in the group the case of repeat operation, the last echocardio- without statins. The odds ratio of prosthetic degeneration graphic examination before surgery was considered. progression (defined by this parameter) with statin treatProgression of bioprosthetic aortic valve degenera- ment was 0.13 (95% confidence interval 0.03 to 0.58). tion was assessed by measuring the changes in peak The odds ratio of worsening aortic regurgitation with and mean prosthetic gradients, effective orifice statin treatment was 0.20 (95% confidence interval: 0.04 area, and indexed effective orifice area. Rates were to 0.90). The overall annual rate of progression of peak calculated on an annualized basis (by dividing the prosthetic velocity was similar between porcine and periabsolute change by the time interval between ex- cardial valves (0.13 ⫾ 0.23 vs 0.09 ⫾ 0.13 m/s/year, p ⫽ aminations). 0.31) and between stented and stentless valves (0.13 ⫾ Continuous data are expressed as mean ⫾ SD and 0.20 vs 0.13 ⫾ 0.30 m/s/year, p ⫽ 0.85). TABLE 1 Baseline Clinical and Echocardiographic Characteristics of the Two Groups
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that statin therapy may slow the progression of mild or moderate aortic stenosis in human native valves.1–3 Clinical Factors Present Absent p Value Two other studies10,11 using electron-beam computed tomography Age ⱖ70 yrs 0.11 ⫾ 0.21 0.15 ⫾ 0.24 0.27 Diabetes mellitus 0.17 ⫾ 0.31 0.12 ⫾ 0.21 0.25 showed a significantly decreased rate Hypertension 0.12 ⫾ 0.26 0.14 ⫾ 0.21 0.59 in aortic valve calcium accumulation Coronary artery disease 0.12 ⫾ 0.22 0.13 ⫾ 0.22 0.81 in patients treated with statins comHypercholesterolemia (⬎220 mg/dl) 0.15 ⫾ 0.32 0.12 ⫾ 0.20 0.47 pared with controls. These results 0.12 ⫾ 0.17 0.13 ⫾ 0.27 0.87 Body mass index ⱖ25 (kg/m2) Statin use 0.04 ⫾ 0.07 0.14 ⫾ 0.23 ⬍0.001 are remarkably similar in suggesting that statin treatment could slow the rate of progression of native aortic valve stenosis. The possible mechanism of statin treatment benefit in TABLE 4 Influence of Clinical Factors on Annual Rate of Change in Prosthetic slowing aortic stenosis progression is Indexed Effective Orifice Area (cm2/m2/yr) not clear. The correlation between Clinical Factors Present Absent p Value lipid levels and aortic stenosis proAge ⱖ70 yrs ⫺0.050 ⫾ 0.078 ⫺0.054 ⫾ 0.091 0.79 gression is very controversial. Two Diabetes mellitus ⫺0.045 ⫾ 0.061 ⫺0.056 ⫾ 0.090 0.56 studies1,10 found a significant corHypertension ⫺0.050 ⫾ 0.075 ⫺0.058 ⫾ 0.094 0.58 relation, whereas other studies2,3 Coronary artery disease ⫺0.056 ⫾ 0.091 ⫺0.047 ⫾ 0.073 0.52 showed a lack of correlation beHypercholesterolemia (⬎220 mg/dl) ⫺0.051 ⫾ 0.088 ⫺0.054 ⫾ 0.084 0.85 tween lipid levels and aortic steno⫺0.058 ⫾ 0.083 ⫺0.044 ⫾ 0.080 0.28 Body mass index ⱖ25 (kg/m2) Statin use ⫺0.019 ⫾ 0.031 ⫺0.056 ⫾ 0.086 ⬍0.001 sis progression. In the present study, statin-treated patients had a reduced progression of bioprosThe influence of several clinical factors on biopros- thetic degeneration despite higher cholesterol levthetic aortic valve degeneration was also evaluated. els. This is concordant with results obtained in Results are listed in Tables 3 and 4. The only factor native aortic stenosis,3 and suggests that the beneassociated with progression of bioprosthetic aortic ficial effect of statins in slowing bioprosthetic valve valve degeneration was statin treatment; patients degeneration is not due to their lipid-lowering eftreated with statins had significantly lower rates of fects, but rather to their pleiotropic effects over and bioprosthetic degeneration, as assessed by different above lipid lowering, including anti-inflammatory parameters. Because in the univariate analyses both effects,12 with reduction of C-reactive protein indethe rate of increase in peak velocity and the rate of pendent of lipid changes.13 decrease in indexed effective orifice area were influOur study provides evidence that statin treatment is enced significantly only by statin treatment, while all associated with significantly less bioprosthetic aortic other variables had no effect (p values ⬎0.20 for all valve degeneration. This finding could influence the the other variables), a multivariate analysis was not type of aortic valve prosthesis chosen in patients reperformed. quiring aortic valve replacement, and could therefore ••• contribute to the clinical decision-making in these In our study, although all echocardiographic pa- patients. rameters of bioprosthetic aortic valve function were similar at baseline in the 2 groups, the annual rates of change of all these parameters were significantly re- 1. Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older duced in the statin group. persons. Am J Cardiol 2001;88:693–695. At present, all porcine valves have similar rates of 2. Novaro GM, Tiong IY, Pearce GL, Lauer MS, Sprecher DL, Griffin BP. Effect 8 structural valve degeneration. In our study, more of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of patients had a porcine aortic valve than a pericardial calcific aortic stenosis. Circulation 2001;104:2205–2209. Bellamy MF, Pellikka PA, Klarich KW, Tajik AJ, Enriquez-Sarano M. Assovalve, and there were more stented than stentless 3. ciation of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase invalves. However, there were no differences regarding hibitor treatment, and progression of aortic stenosis in the community. J Am Coll the proportion of porcine versus pericardial prosthe- Cardiol 2002;40:1723–1730. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, ses, or the proportion of stented versus stentless valves 4. Gutgesell H, Reichek N, Sahn D, Schnittger I, et al. Recommendations for between the 2 groups (Table 1). Several studies, con- quantification of the left ventricle by two-dimensional echocardiography. J Am ducted both in animal models and in humans, ad- Soc Echocardiogr 1989;2:358 –367. 5. Chafizadeh ER, Zoghbi WA. Doppler echocardiographic assessment of the St. dressed the question on the role of statin treatment in Jude Medical prosthetic valve in the aortic position using the continuity equation. the progression of aortic valve stenosis. In a choles- Circulation 1991;83:213–223. terol-fed rabbit model, hypercholesterolemia was 6. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insuffiby Doppler color flow mapping. J Am Coll Cardiol 1987;9:952–959. proved to produce atherosclerotic lesions in the aortic ciency 7. Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, Healy NL, Kraft CD, valve, and atorvastatin was proved to influence the Miyake-Hull CY, Schwaegler RG. Prospective study of asymptomatic valvular pathogenic mechanism, reducing the extent of athero- aortic stenosis: clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997;95:2262–2270. sclerotic changes in the aortic valve.9 Over the last 8. Grunkemeier GL, Bodnar E. Comparative assessment of bioprosthesis durayears, a number of nonrandomized studies reported bility in the aortic position. J Heart Valve Dis 1995;4:49 –55. TABLE 3 Influence of Clinical Factors on Annual Rate of Increase in Peak Prosthetic Velocity (m/s/yr)
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9. Rajamannan NM, Subramaniam M, Springett M, Sebo TC, Niekrasz M, McConnell JP, Singh RJ, Stone NJ, Bonow RO, Spelsberg TC. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation 2002;105:2660 –2665. 10. Pohle K, Maffert R, Ropers D, Moshage W, Stilianakis N, Daniel WG, Achenbach S. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001; 104:1927–1932.
11. Shavelle DM, Takasu J, Budoff MJ, Mao S, Zhao XQ, O’Brien KD. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet 2002;359:1125– 1126. 12. Farmer JA. Pleiotropic effects of statins. Curr Atheroscler Rep 2000;2:208 – 217. 13. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation 1999; 100:230 –235.
Intracardiac Echocardiography During Transcatheter Interventions for Congenital Heart Disease John F. Rhodes, Jr., MD, Athar M. Qureshi, MD, Tamar J. Preminger, MD, E. Murat Tuzcu, MD, Ivan P. Casserly, MD, Kent W. Dauterman, MD, Lourdes R. Prieto, MD, C. Igor Mesia, MD, Geoffrey K. Lane, MBBS, Penny A. Radvansky, RN, and Larry A. Latson, MD Although transesophageal echocardiography is often used for guidance during transcatheter interventions, few data exist regarding the use of the newer modality of intracardiac echocardiography. This brief report summarizes our single center experience using intracardiac echocardiographic guidance during transcatheter interventional procedures for congenital heart disease. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:1482–1484)
catheterization for structural heart disease has changed dramatically over the past deIcadenterventional as transcatheter closure devices for septal defects and patent foramen ovale have become partially or completely approved by the Food and Drug Administsration (FDA). Many of these interventions are typically guided by both fluoroscopic and echocardiographic imaging. The standard ultrasound technique for guidance during transcatheter interventions for congenital heart disease has been transesophageal echocardiography (TEE).1 Echocardiography specialists, even in the catheterization laboratory, usually perform TEE.2 However, recent advances have made intracardiac ultrasound imaging by the invasive cardiologist a viable alternative. We report data regarding the efficacy and safety of intracardiac echocardiography (ICE) during interventional catheterization procedures. •••
Data were retrospectively collected for all patients who underwent a cardiac catheterization procedure using ICE between May 2001 and February 2003. All procedures were performed while patients were under conscious sedation. A standard 11Fr venous sheath was placed percutaneously. An AcuNav (Acuson) From the Departments of Cardiovascular Medicine and Pediatric and Congenital Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Dr. Rhodes’ address is: Pediatric Cardiovascular Program, Duke University Medical Center, DUMC-3090, Durham, North Carolina 27710. E-mail: [email protected]. Manuscript received March 13, 2003; revised manuscript received and accepted August 21, 2003.
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10Fr multifrequency, single-plane ICE catheter was connected to a Sequoia or Cypress ultrasound console (Siemens Medical Solutions, Mountain View, California). The catheter was pretested in a saline solution to confirm imaging before placement in the patient and then advanced through the sheath with the operator’s fingers close to the tip to avoid damaging the ultrasound crystals. We preferred to advance the catheter under fluoroscopic guidance to the right atrium to ensure safe passage through the vasculature. Careful steering of the catheter tip was critical along the common femoral and common iliac vein, and in the inferior vena cava at the level of the hepatic veins. If there was difficulty advancing the ICE catheter, a long (30-cm) venous sheath can be used to overcome difficulty in getting through the common femoral and common iliac vein. After advancing the catheter in the neutral (unlocked) position to the high right atrium, it was deflected posterior and rightward (patient’s right and control knob left) and locked in a position slightly to the right of the patient’s spine. The catheter was then either advanced superior-inferior by advancing/ withdrawing the catheter or anterior-posterior by rotating counterclockwise/clockwise to change the image. Only minor manipulations were made to avoid overtorquing the catheter and thus loss of position once the catheter was released. •••
During the study period, 203 patients (median age 47 years, range 9 to 85) underwent a transcatheter intervention with ICE guidance. During each catheterization, the invasive physician performed ICE imaging as well as transcatheter intervention. In most of our patients (n ⫽ 191), the standard transfemoral approach with a venous sheath in bilateral veins was used. This approach was used in 7 patients despite the presence of an inferior vena cava filter. The venous sheath for ICE was placed in the same femoral vein as the delivery sheath for 9 patients, and for 2 patients with femoral venous occlusion, the venous sheath for the ICE catheter was placed in the internal jugular vein. Also, for 1 patient with an interrupted inferior 0002-9149/03/$–see front matter doi:10.1016/j.amjcard.2003.08.067