***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Transplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy . We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound . METHODS AND RESULTS Intravascular ultrasound examination was performed in 93 patients at 27.2+/-15.0 and 369 . 7+/-23.9 days after transplantation . The maximally and minimally diseased sites were selected in each segment as defined by Coronary Artery Surgery Study classification . For each matched site , maximal plaque thickness was measured . Lesions ( maximum plaque thickness > /=0.5 mm ) present at baseline examination were defined as donor lesions . On follow-up , lesions that developed at previously normal sites were defined as de novo lesions . The distribution and severity of donor and de novo lesions were similar in proximal , mid , and distal segments . The de novo lesions were less focal ( 43 % vs 74 % ) and more circumferential ( 69 % vs 45 % ) compared with the donor lesions , but there was significant morphological heterogeneity . Similar numbers of patients with and those without donor lesions developed de novo lesions . Moreover , progression of donor lesions was not associated with the presence or absence of de novo lesions . CONCLUSIONS Differentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult . Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction . This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other BACKGROUND Despite improvements in immunosuppressive therapy , the most advantageous combination for cardiac transplant recipients has not been established . This r and omized controlled trial was performed to evaluate the efficacy and safety of 3 immunosuppressive protocol s. METHODS Between 2003 and 2005 , 78 de novo cardiac transplant recipients were r and omized 2:2:1 to receive steroids and tacrolimus plus mycophenolate mofetil ( TAC/MMF ; n = 34 ) , TAC and sirolimus ( TAC/SRL ; n = 29 ) , or SRL and MMF ( SRL/MMF ) plus anti-thymocyte globulin ( ATG ; n = 15 ) . Steroids were withdrawn after 6 months . RESULTS The 5-year survival was 85.3 % for TAC/MMF , 93.1 % for TAC/SRL , and 86.7 % for SRL/MMF ( p = 0.31 for TAC/MMF vs TAC/SIR ; p = 0.47 for TAC/MMF vs SIR/MMF and p = 0.86 for TAC/SIR vs SIR/MMF ) . Despite the use of ATG , patients in the SRL/MMF group revealed numerically fewer freedom from acute rejection episodes : TAC/MMF , 82.4 % ; TAC/SRL , 85.2 % ; SRL/MMF , 73.3 % ( p = 0.33 ) . Mean creatinine at 5 years revealed preservation of renal function in the SRL/MMF vs the TAC/MMF group ( p = 0.045 ) : TAC/MMF , 1.70±0.91 mg/dl ; TAC/SRL , 1.44±0.65 mg/dl ; and SRL/MMF , 1.25±0.46 mg/dl . Freedom from cardiac allograft vasculopathy was improved in the SRL/MMF group ( 93.3 % ) compared with TAC/MMF ( 73.5 % ) and TAC/SRL ( 80.8 % ) groups , reaching no statistical significance . Freedom from cytomegalovirus infection was TAC/MMF , 72.2 % ; TAC/SRL , 89.7 % ; and SRL/MMF , 86.7 % . There was a trend toward improved freedom from cytomegalovirus infection with TAC/SRL vs TAC/MMF ( p = 0.076 ) . More frequent discontinuations of study medication occurred in SRL-based immunosuppression protocol s ( TAC/SRL vs TAC/MMF , p = 0.034 ; SRL/MMF vs TAC/MMF , p = 0.003 ) . CONCLUSIONS The 3 strategies yield no survival advantage at 5 years , with higher numeric rates of rejection and adverse effects in the calcineurin inhibitor-free arm . A trend was observed in favor of freedom from cardiac allograft vasculopathy and preservation of renal function in the calcineurin inhibitor-free arm . However , the clinical relevance on outcomes is unclear because only few patients were receiving the assigned treatment protocol BACKGROUND 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 . METHODS This pilot , r and omized , 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 . RESULTS Fifty-two patients were r and omized .  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 ) . CONCLUSIONS 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 We examined the relationship between donor‐specific HLA antibody ( DSA ) presence and graft function , hemodynamics , cardiac allograft vasculopathy ( CAV ) , and major adverse cardiac events ( MACE ) in stable long‐term heart‐transplanted ( HTx ) patients OBJECTIVES A pre-planned sub study of a larger multicenter r and omized trial was undertaken to compare the efficacy of everolimus with reduced-dose cyclosporine in the prevention of cardiac allograft vasculopathy ( CAV ) after heart transplantation to that of mycophenolate mofetil ( MMF ) with st and ard-dose cyclosporine . BACKGROUND CAV is a major cause of long-term mortality following heart transplantation .  Everolimus has been shown to reduce the severity and incidence of CAV as measured by first year intravascular ultrasound ( IVUS ) . MMF , in combination with cyclosporine , has also been shown to have a beneficial effect in slowing the progression of CAV . METHODS Study patients were a pre-specified subgroup of the 553-patient Everolimus versus mycophenolate mofetil in heart transplantation : a r and omized , multicenter trial who underwent heart transplantation and were r and omized to everolimus 1.5 mg or MMF 3 g/day . IVUS was performed at baseline and at 12 months . Evaluable IVUS data were available in 189 patients ( 34.6 % ) . RESULTS Increase in average maximal intimal thickness ( MIT ) from baseline to month 12 was significantly smaller in the everolimus 1.5 mg group compared with the MMF group ( 0.03 mm vs. 0.07 mm , p < 0.001 ) . The incidence of CAV , defined as an increase in MIT from baseline to month 12 of greater than 0.5 mm , was 12.5 % with everolimus versus 26.7 % with MMF ( p = 0.018 ) . These findings remained irrespective of sex , age , diabetic status , donor disease , and across lipid categories . CONCLUSIONS Everolimus was significantly more efficacious than MMF in preventing CAV as measured by IVUS among heart-transplant recipients after 1 year , a finding , which was maintained in a range of patient sub population s. CV surgery : transplantation , ventricular assistance , cardiomyopathy AIMS Cardiac allograft vasculopathy ( CAV ) is a major limitation to long-term survival following cardiac transplantation . Conventional imaging modalities such as angiography and intravascular ultrasound fail to characterize CAV plaque morphology . Our aim was to characterize CAV in vivo using the high spatial resolution of intracoronary optical coherence tomography ( OCT ) . METHODS AND RESULTS We prospect ively enrolled 53 cardiac transplant patients to undergo OCT of the left anterior descending coronary artery ( LAD ) in addition to annual CAV screening by coronary angiography and intravascular ultrasound ( IVUS ) .  The proximal 30 mm of the LAD was divided into three segments of 10 mm each ( n = 156 ) . Segments with CAV plaque on IVUS were analysed by OCT for specific CAV morphological characteristics within the framework of three groups according to follow-up time after heart transplantation : ( i ) 0 - 3 months ( n = 18 ) , ( ii ) 12 - 36 months ( n = 55 ) , and ( iii ) ≥48 months ( n = 83 ) . The prevalence of atherosclerotic characteristics such as eccentric plaques , calcification , and lipid pools increased from 6 , 0 , and 6 % in group 1 to 78 , 42 , and 61 % in group 3 , respectively ( all P < 0.001 ) . The prevalence of vulnerable plaque features such as thin-cap fibroatheroma , macrophages , and microchannels increased from 0 % in group 1 to 12 , 29 , and 33 % in group 3 , respectively ( P = 0.19 , P = 0.006 , and P = 0.003 ) . Complicated coronary lesions such as intimal laceration , intraluminal thrombus , and layered complex plaque increased from 0 % in group 1 to 18 , 19 , and 57 % in group 3 ( P = 0.009 , P < 0.001 , and P < 0.001 ) . Plaque rupture was identified in 4 % of group 3 segments . CONCLUSION The current study gives new insight into CAV that extends far beyond the current concept of concentric and fibrosing vasculopathy , that is , the development of atherosclerosis with vulnerable plaque and complicated coronary lesions BACKGROUND Coronary artery disease occurs in an accelerated fashion in the  donor heart after heart transplantation ( TxCAD )  , but the cause is poorly understood . The risk of developing TxCAD is increased by cytomegalovirus ( CMV ) infection and decreased by use of calcium blockers . Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness , and we now propose to determine whether this therapy also prevents TxCAD . METHODS AND RESULTS One hundred forty-nine consecutive patients ( 131 men and 18 women aged 48+/-13 years ) were r and omized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation . Immunosuppression consisted of muromonab-CD3 ( OKT-3 ) prophylaxis and maintenance with cyclosporine , prednisone , and azathioprine . Mean follow-up time was 4.7+/-1.3 years . In a post hoc analysis of this trial design ed to assess efficacy of ganciclovir for prevention of CMV disease , we compared the actuarial incidence of TxCAD , defined by annual angiography as the presence of any stenosis . Because calcium blockers have been shown to prevent TxCAD , we analyzed the results by stratifying patients according to use of calcium blockers . TxCAD could not be evaluated in 28 patients because of early death or limited follow-up . Among the evaluable patients , actuarial incidence of TxCAD at follow-up ( mean , 4.7 years ) in ganciclovir-treated patients ( n=62 ) compared with placebo ( n=59 ) was 43+/-8 % versus 60+/-10 % ( P<0.1 ) . By Cox multivariate analysis , independent predictors of TxCAD were donor age > 40 years ( relative risk , 2.7 ; CI , 1.3 to 5.5 ; P<0.01 ) and no ganciclovir 
    Output:
    
While confirming known concepts , we found supportive evidence that CAV pathophysiology may vary according to the time post-transplant and the prevalence of metabolic versus immune-mediated risk factors .
Selective revascularization of focal lesions in patients with CAV may result in some clinical benefit , but CAV prevention , rather than treatment , by controlling risk factors and by using targeted immunosuppressive therapies is the most evidence -based approach to reduce disease progression