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Glucose intolerance, as reflected by hemoglobin A1c level, is associated with the incidence and severity of transplant coronary artery disease
Study Question: Does impaired glucose tolerance influence development of transplant coronary artery disease (CAD)? Methods: A total of 151 consecutive survivors (88 men, 63 women) of orthotopic heart transplantation 3.5– 4.7 years (mean 4.1) after their surgery were studied with routine annual coronary angiography. Plasma hemoglobin A1c and intracoronary ultrasound were also done. Transplant CAD was graded by angiography as a) none, b) mild (stenosis in any vessel ⱕ30%), c) moderate (31– 69%) or d) severe (ⱖ70%) and by intracoronary ultrasound as mean intimal thickness ⱖ0.3 mm in any coronary segment. Results: Plasma hemoglobin A1c was associated with increased severity of transplant CAD as evidenced by angiographic grade and correlated with disease severity (r⫽0.24, p⬍0.05). Mean intimal thickness, on intracoronary ultrasound, ⱖ0.3 mm was associated with higher levels of plasma hemoglobin A1c. A multivariate logistic regression analysis revealed that plasma hemoglobin A1c was an independent predictor of transplant CAD (as detected by angiography or intracoronary ultrasound). Conclusions: The authors concluded that impaired glucose tolerance contributes to the pathogenesis of transplant CAD. Perspective: Because transplant CAD is a leading cause of death, this study is important. Although this is a singlecenter study, these findings suggest that good glycemic control may be important to prevent transplant CAD. This study should provide further impetus to develop regimens of immunosuppressive therapy that do not impair glucose tolerance. RB
to the investigations reviewed all clinical data and determined which patients had acute heart failure (a cohort of 447 patients). Results: The study found that (using a three-factor analysis) a BNP level ⱖ100 pg/mL contributed significantly to the prediction of heart failure over each of the radiologic findings. A multivariate regression analysis showed that both BNP levels ⱖ100 pg/mL and chest X-ray findings (cardiomegaly, cephalization and interstitial edema) added significant, predictive information above historical and clinical predictors of heart failure. Conclusions: The investigators conclude that, in patients presenting to the emergency department with dyspnea, chest radiographs and BNP levels aid in diagnosing heart failure. Perspective: This interesting study demonstrated the value of BNP in patients with acute dyspnea. The question remains whether any cost benefit accrues in performing BNP measurements in patients whose heart failure has been confirmed by history, physical examination and chest radiography. RB
Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline: Results of a Randomized Study Silwa K, Woodiwiss A, Kone VN, et al. Circulation 2004:109: 750 –5. Study Question: Does the immunomodulating agent pentoxifylline enhance left ventricular function in patients with ischemic cardiomyopathy? Methods: This single-center study randomized 38 patients with ischemic cardiomyopathy to receive either 400 mg tid of pentoxifylline or placebo in addition to standard therapy. Serial echocardiogram, radionuclide ventriculography, biochemistry and clinical examination were performed at baseline and after 6 months. Study data were assessed in a blinded fashion. Results: Pentoxifylline improved left ventricular ejection fraction (LVEF), functional class and improved systolic blood pressure as compared to the placebo group. Plasma concentrations of inflammatory markers such as CRP, TNF-␣, BNP and a marker of apoptosis Fas/Apo-1 were reduced in the pentoxifylline group. Conclusions: The authors concluded that pentoxifylline when added to standard therapy in patients with ischemic cardiomyopathy improves clinical status and LVEF. Perspective: This very small study had only 20 patients in the treatment group and 18 in the placebo group. The promising results must be confirmed in a much larger trial before this can be accepted as standard therapy. RB/KE
Selection of Patients for Heart Transplantation in the Current Era of Heart Failure Therapy Butler J, Khadim G, Paul KM, et al. J Am Coll Cardiol 2004;43: 787–93. Study Question: What is the role of peak exercise oxygen consumption and heart failure survival score (HFSS) in predicting survival with the widespread use of beta-blockers, spironolactone and defibrillators? Methods: Peak VO2 levels and HFSS were compared between 320 patients before 1997 and 187 patients from after 1999. The latter group was associated with widespread use of beta-blockers, spironolactone and defibrillators. Outcomes, including those who underwent cardiac transplantation, were compared between the two groups. Results: In the group from before 1997 the survival was 78% at 1 year and 67% at 2 years, whereas in the group associated with widespread use of beta-blockers, spironolactone and defibrillators, the survival was 88% at 1 year and 79% at 2 years. One-year survival without urgent transplantation or left ventricular assist device was improved in the current era regardless of the peak VO2, particularly in patients where VO2 was ⬎10 mL/kg/min. Also, in patients from the era where the use of beta-blockers, spironolactone and
Glucose Intolerance, as Reflected by Hemoglobin A1c Level, Is Associated With the Incidence and Severity of Transplant Coronary Artery Disease Kato T, Chan MCY, Gao SZ, et al. J Am Coll Cardiol 2004;43: 1034 – 41.
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to the investigations reviewed all clinical data and determined which patients had acute heart failure (a cohort of 447 patients). Results: The study found that (using a three-factor analysis) a BNP level ⱖ100 pg/mL contributed significantly to the prediction of heart failure over each of the radiologic findings. A multivariate regression analysis showed that both BNP levels ⱖ100 pg/mL and chest X-ray findings (cardiomegaly, cephalization and interstitial edema) added significant, predictive information above historical and clinical predictors of heart failure. Conclusions: The investigators conclude that, in patients presenting to the emergency department with dyspnea, chest radiographs and BNP levels aid in diagnosing heart failure. Perspective: This interesting study demonstrated the value of BNP in patients with acute dyspnea. The question remains whether any cost benefit accrues in performing BNP measurements in patients whose heart failure has been confirmed by history, physical examination and chest radiography. RB
Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline: Results of a Randomized Study Silwa K, Woodiwiss A, Kone VN, et al. Circulation 2004:109: 750 –5. Study Question: Does the immunomodulating agent pentoxifylline enhance left ventricular function in patients with ischemic cardiomyopathy? Methods: This single-center study randomized 38 patients with ischemic cardiomyopathy to receive either 400 mg tid of pentoxifylline or placebo in addition to standard therapy. Serial echocardiogram, radionuclide ventriculography, biochemistry and clinical examination were performed at baseline and after 6 months. Study data were assessed in a blinded fashion. Results: Pentoxifylline improved left ventricular ejection fraction (LVEF), functional class and improved systolic blood pressure as compared to the placebo group. Plasma concentrations of inflammatory markers such as CRP, TNF-␣, BNP and a marker of apoptosis Fas/Apo-1 were reduced in the pentoxifylline group. Conclusions: The authors concluded that pentoxifylline when added to standard therapy in patients with ischemic cardiomyopathy improves clinical status and LVEF. Perspective: This very small study had only 20 patients in the treatment group and 18 in the placebo group. The promising results must be confirmed in a much larger trial before this can be accepted as standard therapy. RB/KE
Selection of Patients for Heart Transplantation in the Current Era of Heart Failure Therapy Butler J, Khadim G, Paul KM, et al. J Am Coll Cardiol 2004;43: 787–93. Study Question: What is the role of peak exercise oxygen consumption and heart failure survival score (HFSS) in predicting survival with the widespread use of beta-blockers, spironolactone and defibrillators? Methods: Peak VO2 levels and HFSS were compared between 320 patients before 1997 and 187 patients from after 1999. The latter group was associated with widespread use of beta-blockers, spironolactone and defibrillators. Outcomes, including those who underwent cardiac transplantation, were compared between the two groups. Results: In the group from before 1997 the survival was 78% at 1 year and 67% at 2 years, whereas in the group associated with widespread use of beta-blockers, spironolactone and defibrillators, the survival was 88% at 1 year and 79% at 2 years. One-year survival without urgent transplantation or left ventricular assist device was improved in the current era regardless of the peak VO2, particularly in patients where VO2 was ⬎10 mL/kg/min. Also, in patients from the era where the use of beta-blockers, spironolactone and
Glucose Intolerance, as Reflected by Hemoglobin A1c Level, Is Associated With the Incidence and Severity of Transplant Coronary Artery Disease Kato T, Chan MCY, Gao SZ, et al. J Am Coll Cardiol 2004;43: 1034 – 41.
ACC CURRENT JOURNAL REVIEW May 2004
48