Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure.

OBJECTIVES: The purpose of this study was to assess the tolerability and efficacy of carvedilol in patients with New York Heart Association (NYHA) functional class IV symptoms. BACKGROUND: Carvedilol, a nonselective beta-adrenergic blocking drug with alpha-adrenergic blocking and antioxidant properties, has been shown to improve left ventricular function and clinical outcome in patients with mild to moderate chronic heart failure. METHODS: We retrospectively analyzed the outcomes of 230 patients with heart failure treated with carvedilol who were stratified according to baseline functional class: 63 patients were NYHA class IV and 167 were NYHA class I, II or III. Carvedilol was commenced at 3.125 mg b.i.d. and titrated to 25 mg b.i.d. as tolerated. Patients with class IV symptoms were older (p = 0.03), had lower left ventricular fractional shortening (p < 0.001), had lower six-min walk distance (p < 0.001) and were receiving more heart failure medications at baseline compared with less symptomatic patients. RESULTS: Nonfatal adverse events while taking carvedilol occurred more frequently in class IV patients (43% vs. 24%, p < 0.0001), and more often resulted in permanent withdrawal of the drug (25% vs. 13%, p < 0.01). Thirty-seven (59%) patients who were NYHA class IV at baseline had improved by one or more functional class at 3 months, 8 (13%) were unchanged and 18 (29%) had deteriorated or died. Among the less symptomatic group, 62 (37%) patients had improved their NYHA status at 3 months, 73 (44%) were unchanged and 32 (19%) had deteriorated or died. The differences in symptomatic outcome at three months between the two groups were statistically significant (p = 0.001, chi-square analysis). Both groups demonstrated similar significant improvements in left ventricular dimensions and systolic function. CONCLUSIONS: Patients with chronic NYHA class IV heart failure are more likely to develop adverse events during initiation and dose titration when compared with less symptomatic patients but are more likely to show symptomatic improvement in the long term. We conclude that carvedilol is a useful adjunctive therapy for patients with NYHA class IV heart failure; however, they require close observation during initiation and titration of the drug.

Efficacy and safety of pravastatin vs simvastatin after cardiac transplantation.

Prior studies of cardiac transplant recipients have shown that pravastatin reduces 12-month rejection and mortality after cardiac transplantation and simvastatin reduces 4-year mortality, low-density lipoprotein (LDL) cholesterol levels, and intimal thickening. In a 12-month observational study, cardiac transplant recipients received open-label pravastatin 40 mg (n = 42) or simvastatin 20 mg daily (n = 45) on an alternating basis from the time of transplantation. Lipid levels, safety, and post-transplant outcomes were compared. We found no significant differences in total LDL or high-density lipoprotein cholesterol, triglycerides, linearized infection or rejection rates, liver function tests, or immunosuppressant dosages between groups at 1, 3, 6, or 12 months. Rhabdomyolysis or myositis occurred only in patients on simvastatin (n = 6, 13.3%) with no episodes for patients on pravastatin (p = 0. 032). Survival at 12 months on an actual treatment basis was 97.6% for patients on pravastatin and 83.7% for those on simvastatin (p = 0.078). Immunosuppression-related deaths occurred in only 2.4% (1 patient) on pravastatin vs 15.6% (n = 7) on simvastatin (p = 0.06). Pravastatin and simvastatin resulted in comparable lipid profiles. Pravastatin use was however free from the high rates of rhabdomyolysis and myositis seen with simvastatin use. Pravastatin was additionally associated with a trend toward superior survival, attributable to fewer immunosuppression-related deaths. For safety and pharmacokinetic reasons, pravastatin should be considered the statin of choice after heart transplantation.

Lung transplantation for chronic obstructive pulmonary disease at St Vincent's Hospital.

BACKGROUND: Lung transplantation (LTx) offers selected patients with end-stage chronic obstructive pulmonary disease (COPD) an improved quality of life and possibly enhanced survival. AIM: To determine local outcomes of LTx for COPD we analysed 173 consecutive heart-LTx (n = 8), single LTx (SLTx; n = 99) and bilateral LTx (BLTx; n = 66) carried out at a single institution during 1989-2003 for smoking-related emphysema (E) (n = 112) and emphysema related to alpha-1 antitrypsin deficiency (AATD) (n = 61). METHODS: There were 98 men and 75 women with a mean age of 50 +/- 6 years (standard deviation) (range 32-63 years). Median waiting time was 113 days (interquartile range (IQR) 50-230 days), and median inpatient stay was 13 days (IQR 9-21 days). RESULTS: Perioperative survival (30 days) was 95% with deaths from sepsis (n = 5), cerebrovascular accident (n = 3) and multiorgan failure (n = 1). Mean follow-up period was 1693 +/- 1302 days (2-4,805 days). The 1-, 5- and 10-year survivals (%) were similar for patients with E and AATD (P = 0.480 log rank) at 86 +/- 5, 57 +/- 7 and 31 +/- 11, respectively, but 1- and 5-year survivals for E were higher after BLTx than after SLTx (97 +/- 2 and 81 +/- 8 vs 85 +/- 4 and 47 +/- 6) (P = 0.015). Pretransplant body mass index, forced expiratory volume in 1 second, forced vital capacity, PaCO(2), PaO(2), six-minute walk distance, home oxygen use, age, sex, cytomegalovirus donor-recipient mismatch, cardiopulmonary bypass use, year of transplant and ischaemic time did not influence survival after LTx. Increasing donor age was a survival risk factor for patients with E but not for those with AATD (hazard ratio 1.043; 95%confidence interval 1.014-1.025). CONCLUSION: Survival after LTx for COPD is similar to survival for other forms of solid organ transplantation, in part reflecting risk factor management.

Impact of concurrent amiodarone treatment on the tolerability and efficacy of carvedilol in patients with chronic heart failure.

OBJECTIVE: To assess the safety and efficacy of carvedilol when administered to heart failure patients already receiving amiodarone. DESIGN: Retrospective analysis of the clinical outcome of 230 patients treated with carvedilol for chronic heart failure, stratified according to whether they were already receiving amiodarone (amiodarone group, 80 patients) or not (non-amiodarone group, 130 patients) at baseline. SETTING: Heart failure clinic at a university affiliated public teaching hospital. MAIN OUTCOME MEASURES: Incidence of adverse events; changes in functional status and echocardiographic dimensions at three months. RESULTS: Adverse reactions to carvedilol occurred in 33 (41%) of the amiodarone group and 43 (29%) of the non-amiodarone group (p = 0.049). Carvedilol was discontinued in 21 (26%) of the amiodarone group and 37 (25%) of the non-amiodarone group (NS). The clinical outcome at three months did not differ significantly between the two groups; 31 (39%) of the amiodarone group improved their New York Heart Association status, 28 (35%) were unchanged, and 21 (26%) deteriorated compared with 67 (45%), 51 (34%), and 32 (21%), respectively, for the non-amiodarone group (NS). Both groups had highly significant decreases in heart rate and left ventricular end systolic dimension, and a significant increase in left ventricular ejection fraction after three months of carvedilol treatment, with no significant differences between the groups. CONCLUSIONS: The beneficial effects of carvedilol on left ventricular remodelling, systolic function, and symptomatic status are not affected by concurrent treatment with amiodarone. Adverse reactions necessitating cessation of carvedilol are no more frequent in patients receiving amiodarone.

Diagnostic value of follow-up transbronchial lung biopsy after lung rejection.

Although transbronchial lung biopsy (TBBx) is widely acknowledged as the "gold standard" for diagnosis of acute rejection, controversy exists regarding the need to perform follow-up procedures. Over a 5-yr period, we performed 1,142 TBBx of which 173 were follow-up TBBx in 99 patients with pulmonary allograft rejection greater than or equal to International Society for Heart and Lung Transplantation (ISHLT) grade A(2) on initial TBBx. Rejection on the previous 173 TBBx was associated with lymphocytic bronchiolitis/bronchitis (LBB) > or = ISHLT grade B(2) in 82 patients and with cytomegalovirus (CMV) pneumonitis in 16 patients. Persistent rejection (> or = A(2)) was observed in 45 of 173 (26%) follow-up TBBx. Persistent B grade rejection (> or = B(2)) was present in 28 patients whereas new B grade rejection developed in 11 patients with > or = A(2) grade rejection. Rejection > or = B(2) was significantly (p < 0.05) associated with rejection > or = A(2). Fifteen follow-up TBBx showed new B grade rejection without signs of > or = A(2) rejection. A new diagnosis of CMV pneumonitis was made in 33 of 173 (19%). CMV pneumonitis occurred in 35 follow-up TBBx, four associated with > or = A(2) rejection and eight with > or = B(2) rejection. The overall incidence of bronchiolitis obliterans syndrome (BOS) in both groups was similar. Patients with persistent rejection on follow-up TBBx developed BOS at a median of 1.3 yr and median of 2.0 yr (p = not significant [NS]) posttransplantation. The practice of follow-up TBBx after rejection within 2 yr posttransplant is clinically useful as it provides valuable diagnostic information.

Prophylactic nasopharyngeal tube insertion prevents acute hypoxaemia due to upper-airway obstruction during flexible bronchoscopy.

Insertion of a nasopharyngeal tube (NT) is a highly effective approach to the management of acute hypoxaemia during flexible bronchoscopy (FB) in lung -transplant recipients. We noted that lung transplant recipients undergoing FB who had been treated previously with NT insertion had further episodes of oxygen desaturation (<90%), despite supplemental oxygen therapy. Prophylactic NT insertion prevented acute hypoxaemia in the majority of lung transplant recipients, with previously documented FB-related oxygen desaturation secondary to UAO. Additional jaw support may be needed in some patients with severe upper-airway obstruction.