- [Show abstract] [Hide abstract] ABSTRACT: Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold. This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters. Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02). Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries.
- [Show abstract] [Hide abstract] ABSTRACT: Cardiac allograft vasculopathy (CAV) is the major cause limiting long term graft survival after heart transplantation (HT), and is characterized by changes in coronary artery geometry, such as intimal thickening and vessel remodeling. Given the limited strategies available to reduce its impact on outcome, early diagnosis of CAV - for which intravascular ultrasound (IVUS) is the gold standard - is crucial to appropriately modulate therapy and to reduce contributing risk factors. However, a highly reproducible image-analysis method is required to capture the complex mechanisms beyond CAV-related changes in coronary geometry.
- [Show abstract] [Hide abstract] ABSTRACT: Whereas the efficacy of statins after heart transplantation (HT) in controlled study settings has been clearly demonstrated, more extensive data are required on the safety and effectiveness of long-term treatment in routine clinical practice. We analyzed the risks and benefits in clinical practice of treatment with statins in all patients who survived HT for at least a month from December 1985 through 2001. During a mean follow-up of 4.8+/-3.8 years, 186 patients were treated with statins (for a median duration [25th to 75th percentile] of 29 [12 to 54] months), while 48 received dietary therapy alone. Patients treated with statins (pravastatin, 48%; atorvastatin, 37%; simvastatin, 14%) presented linearized rates of rhabdomyolisis, myositis, and significant transaminase elevation of 0.37%, 0.74%, and 0.37% per year of treatment, respectively (no fatal event occurred). Low-density lipoprotein decreased after statins by 19% (P<.001). At multivariate analysis, treatment with statins was independently associated with reduced risk of cardiac allograft vasculopathy and overall mortality (P<.001). Our data provide necessary confirmation of the safety and effectiveness in routine clinical practice of appropriately monitored long-term administration of statins (particularly atorvastatin, pravastatin, and simvastatin) in the chronic post-HT phase. Strict follow-up is needed for HT recipients receiving high doses of statins with/without other medications potentially exacerbating the risk of adverse effects.
- [Show abstract] [Hide abstract] ABSTRACT: Few studies are available regarding prognostic stratification of women with severe chronic heart failure (CHF). Although women seem to have a better outcome than men, this may be due to favorable baseline characteristics. We analyzed a cohort of CHF patients referred for heart transplantation (HT) who underwent clinical/laboratory/instrumental evaluation. Women and men were frequency matched for baseline age (53 +/- 14 vs 53 +/- 9 years, p = 0.92), left ventricular ejection fraction (33 +/- 10 vs 31 +/- 8%, p = 0.90) and ischemic etiology (17 vs 22%, p = 0.50). A total of 198 patients were analyzed (109 women matched to 89 men). In addition to matching parameters, prevalence of severe symptoms, diabetes and hypertension were also comparable (p > or = 0.25). After 3 years, cardiovascular death or need for HT (CD/HT) event-free survival was 78 +/- 4% in women and 50 +/- 6% in men (p = 0.005). On multivariate analysis, female gender was associated with a lower risk of CD/HT (relative risk [RR] 0.52; 95% confidence interval [CI] 0.30 to 0.89; p = 0.017), independently of symptoms, blood pressure (BP), left ventricular end-diastolic diameter (LVEDD) and mitral regurgitation (MR). Nevertheless, CD/HT event-free survival at 3 years was 49 +/- 9% for women with New York Heart Association (NYHA) Class III or IV status, who presented with either severe MR, mean BP < or =60 mm Hg or LVEDD > or =35 mm/m2. In advanced CHF, women patients seem to have a better prognosis irrespective of baseline characteristics, supporting the hypothesis that female gender is protective against myocardial injury. However, women with severe symptoms accompanied by either hypotension, severe left ventricular enlargement or MR are at high risk and deserve cautious follow-up and consideration for HT.
- [Show abstract] [Hide abstract] ABSTRACT: Chronic heart failure (CHF) patients with intermediate cardiopulmonary capacity referred for heart transplantation are at "medium risk," and are not amenable to further stratification based solely on peak VO(2.) Accordingly, we analyzed whether time-related and/or non-time-related parameters could provide incremental prognostic information in CHF patients with intermediate cardiopulmonary capacity. We analyzed 134 patients with a peak VO(2) of 10 to 18 ml/kg/min (age 54 +/- 9 years, 66% males) and a left ventricular ejection fraction (LVEF) of 27% +/- 8% who underwent an extensive clinical/instrumental (electrocardiogram, echocardiogram, cardiopulmonary exercise test) index evaluation; for all patients, an equivalent pre-study evaluation (performed >or=6 months before) was also available. Among index-evaluation parameters, systolic blood pressure (p < 0.001), LVEF (p = 0.036), and presence of severe mitral regurgitation (p = 0.006) independently predicted cardiac death/need for heart transplantation. Stable clinical condition from pre-study to index-evaluation accompanied by <10% QRS widening and <10% decrease in peak VO(2) provided incremental prognostic information with respect to all index-evaluation parameters (p = 0.014). CHF patients with intermediate peak VO(2) who display "stable" CHF present a lower incidence of adverse cardiac events, particularly in the absence of hypotension, severe mitral regurgitation, and severe reduction of LVEF. Such a stratification might be clinically useful for deciding between medical treatment alone and consideration for heart transplantation.
- [Show abstract] [Hide abstract] ABSTRACT: Evidence of a lack of relationship between psychiatric disorders and physical status during a heart transplantation (HT) program would configure mental well-being as an independent endpoint deserving specific interventions. We report a prospective, longitudinal study on patients (n=127) undergoing HT in order to investigate the relationship between psychiatric disorders and physical status. At pre-HT evaluation, at least one psychiatric disorder according to the DSM-IV diagnoses was present in 27 patients (21%); the prevalence of psychiatric disorders was not related (p > or = 0.150) to physical status (assessed by clinical, electrocardiographic, echocardiographic, and hemodynamic parameters). At post-HT evaluation 1 year after HT, all clinical-instrumental parameters significantly improved (p < or = 0.016), but not the prevalence of psychiatric disorders, which were diagnosed in 34 patients (p = 0.016 vs pre-HT). During the HT program, no significant relationship exists between physical status and prevalence of psychiatric disorders, which increases after the operation. This finding indicates the need for the mandatory provision of adequate psychological support during all of the phases of the HT experience.
University of Bologna
Bolonia, Emilia-Romagna, Italy
- Institute of Cardiology