934

Letters to the Editor

The Journal of Heart and Lung Transplantation August 2008

Martin Cadeiras, MD a Manuel Bayern, PhD Candidate a Elizabeth Burke, RN, NP a Russell Dedrick, PhD b Anatasia Gangadin, BS a Farhana Latif, MD a Khurram Shazad, MD a Anshu Sinha, PhD Candidate a Esteban G. Tabak, PhD c Charles C. Marboe, MD a Andrea C. Califano, PhD a Mario C. Deng, MD, FACC, FESC a a College of Physicians and Surgeons Columbia University New York, NY, USA b XDx, Inc. Brisbane, CA, USA c Courant Institute of Mathematical Science New York University New York, NY, USA

CLENBUTEROL IMPAIRS MUSCLE QUALITY AND IS POTENTIALLY DANGEROUS To the Editor: In their study, Kamalakkannan et al1 investigated the effect of an anabolic agent on muscle strength and exercise capacity in patients with chronic heart failure (CHF). Their investigation of clenbuterol is of great interest and complements an earlier study by Harrington et al,2 who used salbutamol in the treatment of CHF and showed a potential negative effect of this 2-agonist. Harrington et al found that salbutamol failed to improve exercise capacity and increased the risk of arrhythmia, and therefore they proposed a trial with clenbuterol as a more potent anabolic agent. Nevertheless, the results presented by Kamalakkannan et al leave more questions unanswered. The exercise capacity (peakVO2) did not increase after clenbuterol, and if data are analyzed in detail, one must assume a weakening of muscle as the net effect. This can be derived from their data showing a gain in lean mass in the clenbuterol-treated patients (26.1 5.1 to 27.1 5.1 kg) while peakVO2 remained unchanged (13.8 4.5 to 13.9 4.3 ml/kg/min), and hence the proportion of oxygen per kilogram lean mass, which is a indicator of muscle quality, could be calculated as approximately 47.1 ml/kglean/min pre-clenbuterol and 45.6 ml/ kglean/min post-clenbuterol. Because oxygen supply by heart and lungs remained constant, as indicated by the unchanged ejection fraction on echocardiography and by the unchanged peakVO2, the decline in peakVO2/lean mass illustrates a worsening of muscle quality despite an increase in absolute muscle force. This impaired muscle quality may result from insufcient muscle perfusion, low mitochondrial content, endothelial dysfunction or from a shift to fast-twitch bers. Thus, even the positive anabolic effects of clenbuterol must be interpreted with caution, and must be placed in context with the severe adverse effects. The increase in heart rate in 1 patient of their study was covered only by an increase in metoprolol dose, another patient developed a ventricular tachycardia, and 60% of patients on clenbuterol had muscle cramps and tremors. This is in line with the typical side effects known from the literature and from the criticisms presented by the ESC.3 In conclusion, the study by Kamalakkannan et al was very informative, but the result is to the disadvantage of clenbuterol and should give further evidence to refuse the use of 2-agonists in CHF. Dirk Habedank, MD Martin Steeg, MD Stefan D. Anker, MD, PhD Department of Clinical Medicine

REFERENCES
1. Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005;24: 1710 20. 2. Rodriguez ER, Skojec DV, Tan CD, et al. Antibody-mediated rejection in human cardiac allografts: evaluation of immunoglobulins and complement activation products C4d and C3d as markers. Am J Transplant 2005;5:2778 85. 3. Reed EF, Demetris AJ, Hammond E, et al. Acute antibodymediated rejection of cardiac transplants. J Heart Lung Transplant 2006;25:1539. 4. Deng MC, Eisen HJ, Mehra RM, et al. Non-invasive detection of rejection in cardiac allograft recipients using gene expression proling. Am J Transplant 2006;6:150 60. 5. Tusher VG, Tibshirani R, Chu G. Signicance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001;98:5116 21. 6. Zeeberg BR, Qin H, Narasimhan S, et al. High-Throughput GoMiner, an industrial-strength integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of common variable immune deciency (CVID). BMC Bioinformatics 2005;6:168. 7. Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genomewide expression proles. Proc Natl Acad Sci USA 2005;102: 1554550. 8. Mueller TF, Einecke G, Reeve J, et al. Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am J Transplant 2007;7:271222. 9. Racusen LC. Immunopathology of organ transplantation. Springer Semin Immunopathol 2003;25:141 65. 10. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 1998;95:14863 8.

The Journal of Heart and Lung Transplantation Volume 27, Number 8

Letters to the Editor

935

Charite Campus Virchow Applied Cachexia Research Berlin, Germany REFERENCES

1. Kamalakkannan G, Petrilli CM, George I, et al. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant 2008;27:457 61. 2. Harrington D, Chua TP, Coats AJ. The effect of salbutamol on skeletal muscle in chronic heart failure. Int J Cardiol 2000;73: 257 65. 3. Deligiannis A, Bjrnstad H, Carre F, et al. ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes. Eur J Cardiovasc Prev Rehabil 2006;13:68794.

A WORD OF CAUTION FOR PATIENTS UNDERGOING LUNG TRANSPLANTATION WITH ASSOCIATED MITRAL REGURGITATION To the Editor: Lung transplantation has become a well-accepted therapy for end-stage lung disease. Unfortunately, the lung transplant recipient is at risk for developing several complications, with ischemiareperfusion injury, acute rejection and infections being the most common in the peri-operative period.1 The clinical presentations of these complications are very similar and are manifested as respiratory distress and, in severe cases of respiratory failure, require prolonged ventilation. The presence of mitral regurgitation (MR), with its hemodynamic consequences and possibility of development of pulmonary edema, further complicates the post-operative course. We treated a 34-year-old woman with advanced lung disease secondary to systemic lupus erythematosus (SLE) together with lupus affection of the heart with resultant MR. She was on corticosteroid therapy for SLE and oral anti-coagulants due to previous cerebral stroke. Echocardiography showed prolapse of both mitral leaflets with Grade 3 /4 MR, left atrial diameter of 42 mm, left ventricular end-systolic and end-diastolic diameters of 32 and 46 mm, respectively, and an ejection fraction of 60%. Cardiac catheterization revealed a pulmonary artery pressure of 55/10 mm Hg. Based on these data the treating cardiologist recommended follow-up treatment for MR. The patient underwent bilateral sequential lung transplantation with cardiopulmonary bypass (CPB). The postoperative course was complicated. After 3 weeks of mechanical ventilationinitially through the endotracheal tube then through the tracheotomy tube disconnection from ventilator was tried several times, but each time the patient developed pulmonary edema, then underwent desaturation and was reconnected to the ventilator again. After exclusion of other potential factors, MR

was considered the incriminating factor for failure to wean and we decided to proceed to mitral valve surgery, which was done 5 weeks after transplantation. Intraoperatively, the posterior leaet and the related annulus were heavily calcied and the valve seemed damaged beyond repair; therefore, the valve was replaced with a St Jude mechanical valve. After valve replacement, the patient was successfully disconnected from the ventilator on Day 3 post-operatively and was shifted to the transplantation ward on Day 8 post-operatively. The subsequent course was uneventual. The optimal time for MR surgery remains a matter of controversy.2,3 The current ACC/AHA guidelines recommend surgery for symptomatic patients or when asymptomatic patients develop early signs of left ventricular dysfunction, pulmonary hypertension or atrial brillation.4 However, in patients with advanced lung disease it is difcult to specify whether the symptoms are of cardiac or pulmonary origin. In addition, a good percentage of these patients have pulmonary hypertension secondary to the original lung disease, which further complicates the decision-making process. Moreover, the transplanted lung goes through transitional changes in the early post-transplant period characterized by altered function of the alveolar capillary barrier with increased permeability, alveolar uid accumulation and decreased uid clearanceall of which mandate special consideration for this group of patients. Even before development of the ACC/AHA hemodynamic criteria for surgery, we supported consideration of early surgery for moderately severe or severe MR in patients listed for double-lung transplantation. Valve surgery should be planned at the time of transplantation. Abdel-Mohsen Hamad, MD a Giovanna Rizzardi, MD a Tommaso Bottio, MD b Gino Gerosa, MD b Federico Rea, MD a a Division of Thoracic Surgery b Division of Cardiac Surgery Department of Cardiothoracic and Vascular Sciences University of Padua Padua, Italy REFERENCES
1. Meyers BF, de la Morena M, Sweet SC, et al. Primary graft dysfunction and other selected complications of lung transplantation: a single-center experience of 983 patients. J Thorac Cardiovasc Surg 2005;129:14219. 2. Rosenhek R, Rader F, Klaar U, et al. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation 2006;113: 2238 44.