Predictors of perceived social support in long-term survivors of cardiac transplant: the role of psychological distress, quality of life, demographic characteristics and clinical course.

AIM: To examine associations between perceived social support, quality of life, psychopathological, demographic and clinical variables in long-term heart transplant survivors. METHODS: Sixty six patients transplanted from 10.2 ± 3.3 years completed the Interpersonal Support Evaluation List, Symptom Questionnaire and World Health Organization Quality of Life-BREF. Parameters of post-transplant medical course were retrieved. Spearman rank order correlation, Mann-Whitney U test, Kruskal-Wallis test and multiple regression analyses were performed. RESULTS: At multiple regression analyses SQ depression significantly predicted Interpersonal Support Evaluation List (ISEL) total and appraisal scores (p = 0.005 and p = 0.047), indicating better satisfaction for support in patients with less depressive symptoms. Low levels of depression and being married or living as married were significantly associated with better ISEL belonging (p = 0.03 and p = 0.008) and self-esteem (p < 0.001 and p = 0.038). Skin cancer significantly correlated with better tangible (p = 0.02) and total (p = 0.05) support. Social quality of life was positively associated with ISEL total (p < 0.01), appraisal (p < 0.05), belonging (p < 0.01) and tangible (p < 0.05) scores; yet, it significantly predicted none of the them. CONCLUSIONS: Depressive symptoms may worsen patients' satisfaction for their interpersonal support. Marital status seems to foster sense of belonging and self-esteem. The paucity of significant associations between ISEL and clinical parameters may reflect the caregivers' continuous provision of support regardless of clinical status.

Psychological predictors of mortality in heart transplanted patients: a prospective, 6-year follow-up study.

BACKGROUND: Some reports suggest a link between poor psychological adjustment to heart transplantation and an increased risk of subsequent adverse clinical outcome. Despite its prognostic and therapeutic implications, this issue is still lacking adequate empirical studies. We prospectively tested the predictive value of a complete set of psychiatric and psychological variables, collected with both self-rating and observer-based instruments at midterm after heart transplantation, on the subsequent 6-year survival status. METHODS: Ninety-five heart transplanted patients underwent the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders-4th Edition and the structured interview for Diagnostic Criteria for Psychosomatic Research and filled three questionnaires assessing the dimensions of psychological distress, quality of life, and psychological well-being. Demographic characteristics and several clinical parameters were also collected. A 6-year follow-up survival was performed. RESULTS: Analyses of survival showed that hostility, depression, purpose in life, the occurrence of at least one cardiac event, chronic renal insufficiency, diabetes, number of drug prescriptions, a New York Heart Association (NYHA) class more than or equal to II, and ischemic origin of the cardiopathy significantly predicted subsequent survival duration. When multivariate analyses were performed, high levels of hostility and the presence of diabetes resulted the independent predictors of survival status. CONCLUSIONS: These findings point out the predictive role of specific components of psychological adjustment to heart transplantation and pose the basis for the evaluation of whether the provision of pharmacologic and psychotherapeutic interventions, aimed at reducing the empirically identified psychological risk factors, may result in a better long-term outcome.

[Coronary allograft vasculopathy: pathophysiological interaction between the immune system, infections and metabolic syndrome]. / La malattia coronarica del cuore trapiantato: interazione fisiopatologica tra sistema immunitario, infezioni e sindrome metabolica.

Cardiac allograft vasculopathy is still the main cause of long-term graft loss after heart transplantation. Indeed, recent advances in immunosuppression management led to a significant improvement in short-term survival, while long-term death rate did not change significantly in the last 20 years. In this paper, we will review the latest advances in the understanding of this peculiar form of atherosclerosis, focusing on the mechanisms that can be potentially targeted by specific therapeutic interventions.

Relevance of cardioverter defibrillators for the prevention of sudden cardiac death on the timing of heart transplantation.

UNLABELLED: Information on the incidence of decompensation of chronic heart failure (CHF) in heart transplantation (HT) candidates eligible for prophylactic implantable cardioverter defibrillators (ICD) could provide insights into the influence of ICD on the timing for HT. METHODS: We investigated the prevalence of candidates satisfying SCD-HeFT and MADIT-II criteria for prophylactic ICD among patients (n = 317) with CHF referred to our tertiary center for HT. In addition to standard clinical and laboratory assessments, baseline evaluation included two-dimensional standard transthoracic echocardiogram and 12-lead electrocardiogram. RESULTS: At baseline, 19% of patients (n = 60) satisfied MADIT II criteria, and 58% (n = 185) fulfilled SCD-HeFT criteria. A total of 60% patients (n = 190) were eligible for prophylactic ICD implantation according to at least one set of criteria. Five-yr CHF decompensation-free survival was 68 +/- 4% in patients eligible for prophylactic ICD (p = 0.003), (RR 2.5, 95% CI 1.35-4.63). CONCLUSIONS: SCD-HeFT could imply a threefold rise in ICD eligibility in tertiary settings. As ICD-eligible patients would likely remain at high risk of progressive ventricular dysfunction, strict follow-up should be considered extremely important to allow a timely referral for HT.

Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure.

BACKGROUND: It is unknown whether time-related changes of pulmonary hypertension (PH) have prognostic relevance in severe chronic heart failure (CHF). METHODS: All CHF patients referred for follow-up from 1996 through 2003 were screened for this study. Eligibility depended on availability of a concomitant clinical, laboratory, electrocardiographic (ECG), echocardiographic and right-heart catheterization (RHC) assessment at index evaluation, as well as absence of pre-capillary PH. RESULTS: One hundred ninety-six patients (age 54 +/- 9 years; 27% women, 73% men; 50% in New York Heart Association [NYHA] Class III or IV) were included. PH at index evaluation was an independent predictor of acute heart failure or cardiovascular death (AHF/CD), with adjusted risk ratio (RR) = 2.30, 95% confidence interval (CI) 1.42 to 3.73 and p < 0.001. A pre-study (> or =6 months) RHC was available for 174 of the 196 patients. Worsening of mean pulmonary artery pressure (mPAP) of > or =30% (a pre-specified cut-off corresponding to the 75th percentile of DeltamPAP%) provided prognostic information independent of all index-evaluation parameters (adjusted RR = 2.60, 95% CI 1.45 to 4.67, p = 0.001), and from time-related changes in the other hemodynamic parameters (p < or = 0.033). CONCLUSIONS: PH retains independent prognostic significance even after adjusting for a large set of clinical/laboratory/instrumental parameters. Furthermore, serial measurements of mPAP seem to provide additional prognostic information as compared with a single assessment. These findings indicate that serial evaluations of PAP may help identify a sub-set of high-risk CHF patients deserving a particularly close follow-up to facilitate timely indications for non-pharmacologic strategies, including (when appropriate) heart transplantation.

Role of severe functional mitral regurgitation in predicting electrical remodeling in idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate incidence and predictors of clinically relevant QRS widening (predefined as > or = 10% with respect to baseline) in idiopathic dilated cardiomyopathy (IDC) and particularly the prognostic role of functional mitral regurgitation (MR). Although QRS widening in left ventricular systolic dysfunction carries relevant prognostic and therapeutic implications, its incidence and predictors in patients with IDC remain unknown. METHODS: We analyzed 114 patients with IDC receiving optimized medical treatment (age 52 +/- 10 years; 44% males; 36% New York Heart Association class III-IV) who underwent clinical, echocardiographic, hemodynamic, and laboratory evaluations and at least two electrocardiograms > or = 6 months after the index evaluation. RESULTS: During follow-up (median 20 months), 19 (17%) patients developed clinically relevant QRS widening, corresponding to an incidence of 8% per year. At multivariable analysis, the presence of echocardiographically detected severe MR (P = 0.029) and mean right atrial pressure (RAP) by right heart catheterization (P = 0.021) independently predicted clinically relevant QRS widening. CONCLUSIONS: Clinically relevant QRS widening is relatively frequent in IDC despite optimized medical treatment, and is independently predicted by MR severity and high RAP. IDC patients presenting either of these risk-factors might benefit from strict follow-up, which could also allow timely detection of the onset of indications for cardiac resynchronization therapy.

Prognostic stratification of women with chronic heart failure referred for heart transplantation: relevance of gender as compared with gender-related characteristics.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Static and dynamic predictors of adverse events in patients with intermediate cardiopulmonary capacity referred for heart transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Relationship between psychiatric disorders and physical status during the course of a heart transplantation program: a prospective, longitudinal study.

BACKGROUND: 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. METHODS: We report a prospective, longitudinal study on patients (n=127) undergoing HT in order to investigate the relationship between psychiatric disorders and physical status. RESULTS: 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). CONCLUSIONS: 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.

Homocysteine-lowering therapy and early progression of transplant vasculopathy: a prospective, randomized, IVUS-based study.

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.

Safety and efficacy of two types of influenza vaccination in heart transplant recipients: a prospective randomised controlled study.

BACKGROUND: Influenza may cause severe disease in immunosuppressed patients. Different vaccines have been proved to be efficacious to prevent influenza in tranplant recipients. Since the last five years the addition of adjuvants to improve the immune response to vaccine preparations has been proposed and evaluated. In this study, two antigenically identical vaccines, but different for the presence of adjuvants were randomised among a cohort of heart transplant recipients to evaluate their safety and immunogenicity. METHODS: 58 patients, receiving an heart transplant more than 6 months before, were randomised to receive one shoot vaccination with Fluad (containing the MF59 adjuvant) or Agrippal (no adjuvant added) or to enter the control, not-vaccinated, group. The immune response to influenza was evaluated separately for type A and type B viruses and for the IgG and the IgM antibodies. Patients were clinically evaluated at least monthly up to 6 months. RESULTS: Influenza symptoms were reported by 33% of patients receiving Fluad, 29% of the Agrippal and 63% of the control group. 4 episodes of acute myocardial rejection >/=3A were identified without difference between the three groups. CONCLUSIONS: The superior efficacy of vaccines containing adjuvants was not found and the data clearly confirmed that vaccination against influenza is safe and effective in heart transplant recipients. The use of vaccine containing adjuvant substances do not ameliorate the clinical performance of the immunisation suggesting that less expensive influenza vaccine preparation without adjuvant substances could be equally useful to protect heart transplant recipients.

Impaired dendritic cell immunophenotype and function in heart transplant patients undergoing active cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus (HCMV) infects dendritic cells (DCs) in vitro and inhibits their maturation properties and their ability to stimulate T-cell proliferation and cytotoxicity. This study analyzed HCMV infection of DCs in vivo. METHODS: We compared blood DCs and monocyte-derived DCs from heart-transplant patients undergoing an acute HCMV infection with DCs obtained from HCMV-negative transplant patients. Diagnosis of active HCMV infection was established by antigenemia test. RESULTS: We detected viral RNA and antigens in defined DC subsets obtained from patients undergoing an active HCMV infection. In addition, we found an impaired immunophenotype in immature DCs from HCMV-positive subjects and a reduced ability of mature DCs from the same group of patients to stimulate allogenic T-cell proliferation. CONCLUSIONS: The impaired immunophenotype and function detected in DCs from transplant patients undergoing an active HCMV infection may be a mechanism used by the virus to interfere with early immune functions and thereby contributing to the HCMV-induced immunosuppression in these patients.

Implications of cardiac resynchronization therapy and prophylactic defibrillator implantation among patients eligible for heart transplantation.

This study analyzed the relations and time-related changes in eligibility for cardiac resynchronization therapy and prophylactic defibrillator implantation in 161 potential candidates for heart transplantation. Although up to 62% of patients who fulfilled the severity criteria for heart transplantation were eligible for either device, this percentage increased as clinical/instrumental parameters of heart failure severity worsened.

Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells.

BACKGROUND: Statins exert anti-inflammatory effects independently of cholesterol-lowering properties. Cytomegalovirus (CMV) infection appears to be implicated in the pathophysiology of atherosclerosis by inducing inflammatory modifications in endothelial cells, especially in immunosuppressed patients. We investigated whether the activity of statins can inhibit replication of CMV in human endothelial cells. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were infected with CMV and coincubated with fluvastatin at 0.1 and 0.2 micromol/L. Fluvastatin inhibited (P<0.001) CMV antigen expression, and this effect was dose related (P<0.001). Quantitative polymerase chain reaction showed that CMV DNA concentration was consistently lower in supernatants from fluvastatin-treated cells than in infected controls, and viral particle concentration was up to 30 times lower in 0.2 micromol/L fluvastatin-treated cells than in infected controls (10.5+/-0.9 versus 0.34+/-0.03 per 10(3) pfu/mL, P<0.001). Addition of mevalonate to treated cultures almost completely abolished fluvastatin inhibition of viral growth. Electrophoretic mobility shift assay showed that fluvastatin reduced nuclear factor-kappaB binding activity in CMV-infected cells. CONCLUSIONS: HMG-CoA inhibition by fluvastatin restrains CMV replication in HUVECs by inhibiting viral antigen expression, DNA synthesis, and viral particle production, conceivably by involving a reduction of nuclear factor-kappaB binding activity.

Combined heart and liver transplantation for familial amyloidotic neuropathy: considerations from the hepatic point of view.

Few cases of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy have been reported, and the technique for the operation is far from being consolidated. Three patients with amyloidogenic transthyretin (ATTR)-related (variant Glu89Gln to ATTR Glu89Gln) cardiomyopathy underwent CHLT at our institution. Patient 1 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All three patients underwent cardiac and sequential hepatic transplantation using the piggyback technique with organs procured from the same donor. Venovenous bypass (VVB) was used only in patient 1, with an uncomplicated procedure. After CHLT, his cardiac performance remained normal, and no progression of amyloidosis was observed. Patient 2 had no intraoperative complications, but experienced postoperative bleeding, renal failure, sepsis, and heart failure and eventually died of multiorgan failure 2 months after transplantation. In patient 3, right hemicolectomy was required intraoperatively because of intestinal ischemia without significant hemodynamic perturbations, whereas extracardiac symptoms of amyloidosis gradually worsened postoperatively. Two patients (no. 1 and 3) currently are alive after 38 and 18 months, respectively. CHLT for ATTR Glu89Gln can be performed successfully, even in patients with advanced disease. However, the most compromised patients are more exposed to intraoperative risks, postoperative complications, and worsening of extracardiac and extrahepatic symptoms. The need for VVB remains to be evaluated.

Serial versus isolated assessment of clinical and instrumental parameters in heart failure: prognostic and therapeutic implications.

BACKGROUND: In heart failure (HF), it is not known whether analysis of serial changes in prognostic parameters provides incremental information with respect to comprehensive isolated clinical and instrumental assessments. METHODS: We analyzed time-related changes in a period > or =6 months in a broad panel of clinical and instrumental (electrocardiographic, echocardiographic, hemodynamic, and cardiopulmonary) parameters in 105 patients with HF (age, 53 +/- 10 years; 88% men; 55% New York Heart Association classification III-IV; EF, 24% +/- 6%). RESULTS: Among the time-related parameters, QRS widening (adjusted RR per 10 ms, 1.21; 95% CI, 1.10-1.48; P =.003) and peak oxygen uptake (pVO2) decrease (adjusted RR per mL/Kg/min, 1.11; 95% CI, 1.01-1.22; P =.034) provided independent, incremental information for predicting cardiac death/need for heart transplantation (CD/HT) with respect to the entire panel of isolated readings. The overall rate of CD/HT-free survival after 12 months was 60% +/- 5%. Patients who were clinically stable with QRS widening and pVO2 decrease values of <10% had a better CD/HT event-free survival rate at 1 year (92% +/- 5% vs 50% +/- 6%; P <.001). CONCLUSIONS: This study indicates that analysis of time-related changes in prognostic parameters provides relevant incremental prognostic information and may help in the risk stratification of patients with HF and the selection of candidates for HT. In particular, patients who were clinically stable and had QRS widening and a pVO2 decreases <10% in a period > or =6 months appear to be characterized by a good prognosis and may not be suitable candidates for HT.

[Clinical problems in heart transplant recipients]. / I problemi clinici del cardiopatico trapiantato.

Heart transplantation has become a more and more effective therapeutic strategy in severe heart failure patients. An opportune management of the several medical, immunological and psychological complications, that may occur during heart transplant recipients' life, is mandatory to succeed in this therapeutic approach. Indeed, thanks to heart transplantation, recipients may recover from a lethal cardiovascular disease, but on the other hand, they may encounter several co-morbidities. An optimized management has to involve not only the referring Transplant Center, but also the single patient's personal cardiologist and general physician. Therefore, the present paper has the educational aim to present the most common clinical problems occurring during heart transplant recipients' follow-up, by reviewing current literature in the light of the experience gained by the Bologna Heart Transplant Unit.

Distance between patients' subjective perceptions and objectively evaluated disease severity in chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a socially relevant condition carrying an adverse prognosis. Systematic analysis is needed of the relationship between quality of life (QoL) - what patients are most interested in - and objective parameters of CHF severity - which largely determines physicians' care. METHODS: We prospectively investigated QoL, as ascertained by the Minnesota Living with Heart Failure Questionnaire, alongside all the currently used objective clinical/instrumental (electrocardiographic, echocardiographic, hemodynamic and functional capacity) indicators of disease severity in 106 consecutive CHF patients. RESULTS: Besides persistence of sinus rhythm (p = 0.007), the only objective parameters that correlated with QoL were NYHA class (p < 0.001) and distance covered during the six minutes walking test (p < 0.001) (two indications of patients' ability to attend to their daily needs). Presence of left bundle branch block was associated with a worse QoL only in patients with CHF due to ischemic heart disease (p = 0.032). All the other clinical/instrumental parameters showed no relation with QoL (p > 0.150 in all cases). CONCLUSIONS: Objective indicators of disease severity, which largely determine physicians' care, appear to have little bearing on QoL, suggesting that current treatment for CHF fails to satisfy patients' perceived needs. The possibility of cost-effective nonpharmaceutical therapeutic protocols (e.g. psychological interventions) specifically designed to improve patients' QoL deserves investigation as a much needed new approach to the management of CHF.

Relevance of cytomegalovirus infection and coronary-artery remodeling in the first year after heart transplantation: a prospective three-dimensional intravascular ultrasound study.

BACKGROUND: Transplant coronary artery disease (TxCAD) is a major cause of long-term mortality after heart transplantation. Although vascular remodeling has been implicated in the pathophysiology of TxCAD, its determinants remain unknown. METHODS: Twenty-nine consecutive heart-transplant recipients prospectively received intravascular ultrasound (IVUS) of the left-anterior descending artery 1 and 12 months after transplant, with volumetric reconstruction of the proximal 30 mm. RESULTS: Overall, patients exhibited intimal volume increase (+83%, P<0.001), wheras vessel volume remained largely unchanged (+4%, P=0.270); consequently, overall lumen volume decreased (-6%, P=0.058). Among the clinical and laboratory variables, cytomegalovirus (CMV) infection requiring treatment (occurring in 12 patients), as assessed by pp65 antigenemia, was independently associated with the impaired ability of the vessel wall to enlarge in response to intimal volume increase, ultimately resulting in lumen loss (OR [95% CI]=0.098 [0.010-0.920]; P=0.042). However, adequate vessel response to intimal hyperplasia with consequent lumen preservation was observed in the remaining 17 patients who did not present CMV infection requiring treatment. CONCLUSIONS: The present study demonstrates that either adequate or inadequate coronary remodeling may occur during the first year after transplantation. Moreover, for the first time, it strongly suggests that remodeling modalities may be negatively influenced by the occurrence of clinically relevant CMV infection. Randomized prospective trials are warranted to investigate whether aggressive treatment of CMV infection may help prevent TxCAD.