RAndomized Comparison of raDIal vs. femorAL Access for Routine Catheterization of Heart Transplant Patients (RADIAL-heart transplant study).

Although a transradial approach (TRA) is considered feasible in many clinical situations, no data are available in patients undergoing orthotopic heart transplantation (OHT). Our goal was to randomly compare TRA versus a transfemoral approach (TFA) in this clinical setting. This single-center, prospective, randomized trial was conducted from January to November 2006, and all OHT patients scheduled for a control coronary angiography were randomized to receive TRA or TFA. The primary endpoint was the amount of contrast used during the procedure. The participating interventional cardiologists were intermediate-volume radial operators, and this was their initial experience of TRA in OHT patients. The analysis was performed according to the intention-to-treat principle. Overall, 49 patients (mean age, 55 ± 13 years; 74% male) were included in the trial: 26 patients were assigned to TRA, and 23 were assigned to TFA. A higher amount of contrast (147 mL [range, 113-175 mL] vs 105 mL [range, 86-127 mL]; P = .009), a longer fluoroscopy time (9.2 minutes [range, 6-12 minutes] vs 3.5 minutes [range, 3-5 minutes]; P < .001), a trend toward increased number of catheters used for left ostium cannulation, and a higher crossover rate (19% vs 0%; P = .03) were associated with TRA compared with TFA. Furthermore, patients treated with TRA exhibit a shorter hospital stay (6 [range 4-8]) compared with the other group (26 [range 24-28]) (P < .001). There were no significant differences between the 2 groups regarding total procedural time, and no vascular complications were reported in either group. For these operators with their first experience of TRA in OHT patients, TFA seemed to be more efficient.

Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study.

BACKGROUND: The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may influence the development of CMV viremia and CMV disease in these patients. METHODS: HT recipients ≥18 years of age (n=199) were included in the study. Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. RESULTS: The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor+/recipient-) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (P<0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P=0.005). CONCLUSIONS: In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMV disease was very low. Having a CMV-positive donor was identified as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.

Usefulness of sirolimus as rescue therapy in heart transplant recipients with renal failure: analysis of the Spanish Multicenter Observational Study (RAPACOR).

BACKGROUND: Chronic renal failure is a common complication of heart transplantation. Sirolimus (SRL) is an immunosuppressive drug that, unlike calcineurin inhibitors (CNIs), is not associated with nephrotoxicity. METHODS: We collected efficacy and safety data from a Spanish registry of heart transplant recipients who were switched from a CNI to SRL due to renal failure. Patients were included if the serum creatinine level before switching was >1.5 mg/dL and/or the estimated creatinine clearance level was below 50 mL/min. RESULTS: Ninety-seven patients started SRL due to renal impairment. When SRL was started, CNIs were progressively tapered and in some cases withdrawn. Mean baseline creatinine level was 2.5 mg/dL and mean creatinine clearance level was 39 mL/min. Only 1 episode of acute rejection was observed in a patient receiving SRL plus cyclosporine (CsA) but the eventual allograft function remained stable. Compared with baseline, a significant improvement in renal function was observed at 6 months among patients who stopped CNIs before the third month after SRL was started, although not among those who continued taking CNIs. Upon multivariate analysis, no predictors of response were observed. SRL was withdrawn in 18% of patients due to adverse events. CONCLUSIONS: Switching to SRL was safe in heart allograft recipients, improving renal function among those previously receiving a CNI. Renal function improves if CNIs are withdrawn soon after starting SRL.

Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.

BACKGROUND: Because myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens. METHODS AND RESULTS: Forty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage. CONCLUSIONS: Apoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

Somatostatin receptor scintigraphy predicts impending cardiac allograft rejection before endomyocardial biopsy.

The invasive nature of endomyocardial biopsy has led to a search for alternative diagnostic modalities for the detection of cardiac allograft rejection. To date, no non-invasive test meets all the requirements for the detection of acute and chronic rejection. The rejection process usually presents with lymphocyte infiltration with or without myocyte necrosis, which indicates the severity of cardiac allograft rejection and the necessity of treatment. Activated lymphocytes express somatostatin receptors; thus somatostatin receptor imaging could be used to target them. The aim of this study was to assess the feasibility of using somatostatin receptor imaging to target activated lymphocytes in the process of cardiac allograft rejection. Thirteen somatostatin receptor imaging studies were performed on ten cardiac allograft recipients 12-4,745 days after transplantation, simultaneously with endomyocardial biopsy, to assess the imaging of activated lymphocytes in comparison with histological findings. Somatostatin receptor imaging was performed 4 h after the injection of 110 MBq of the somatostatin analogue indium-111 pentetreotide. 111In-pentetreotide uptake was visually scored and semi-quantitatively estimated by the calculation of a heart-to-lung ratio (HLR). The visual score correlated with the HLR. Intense/moderate uptake on visual assessment and an HLR >1.6 was observed in eight studies. In three of these studies there was significant rejection in the simultaneous endomyocardial biopsy [International Society of Heart and Lung Transplantation (ISHLT) rejection grade 3A/4]. Intense/moderate uptake was associated with mild or no rejection in the remaining five patients, and in four of them the next endomyocardial biopsy performed 1 week later demonstrated significant rejection requiring treatment. Two patients with low uptake and an HLR <1.6 had no evidence of rejection either in the simultaneous endomyocardial biopsy or in the endomyocardial biopsy performed the following week. These preliminary results indicate the feasibility of targeting activated lymphocytes with somatostatin receptor imaging in the detection of cardiac allograft rejection. Somatostatin receptor imaging may predict impending rejection at least 1 week before the endomyocardial biopsy becomes positive. The late appearance of diagnostic endomyocardial biopsy probably reflects a lag-time between lymphocytic activation and induction of myocyte damage. Furthermore, somatostatin receptor imaging at 4 h may in any case allow earlier intervention in the event of rejection, given the time required for histological processing of endomyocardial biopsy.

Validation of the Agency for Health Care Policy and Research (AHCPR) classification for managing unstable angina.

To validate the AHCPR classification for the prognosis of unstable angina, 225 consecutive patients were recruited with a suspected diagnosis of that condition attending a tertiary hospital from November 1994 through April 1995 and followed for one year. One-hundred fifty-six (69.3%) patients were considered at high risk, 37 (16.5%) at intermediate, and 32 (14.2%) at low risk of cardiac complications. All of the patients with major in-hospital cardiac complications (8 patients) had at least one of the features of the high risk group. The high to intermediate-low hazard ratio (HR) for one-year cardiac complications after the onset of unstable angina was 4.03. Predictors of major complications (myocardial infarction or death) after the follow-up were age > 65 (HR, 5.69); diabetes (HR, 4.94); heart failure (HR, 2.65); and prolonged angina (HR, 2.55). AHCPR classification correctly identified patients with risk of severe outcomes at the hospital. Also, the classification predicted outcomes one year after hospitalization, diabetes being an important determinant of adverse cardiac events.

Sympathetic reinnervation of cardiac allografts evaluated by 123I-MIBG imaging.

UNLABELLED: Some heart-transplant patients present with improved heart rate response to exercise and anginal pain suggesting reinnervation of allografts. Studies performed up to 5 y post-transplantation have suggested that reinnervation is a slow process that occurs only after 1 y post-transplantation. The purpose of this study was to evaluate the extent of sympathetic reinnervation in heart-transplant patients and its relation to cardiac function. METHODS: We performed 123I-metaiodobenzylguanidine (MIBG) studies and rest/exercise radionuclide ventriculography in 31 heart-transplant patients 6 mo to 12 y post-transplantation. Intensity of myocardial MIBG uptake was quantified by a heart-to-mediastinum ratio (HMR), and the regional distribution of MIBG was determined by tomographic studies. RESULTS: HMR correlated positively with time after transplantation (r = 0.607, P < 0.001). Patients studied from 2 to 12 y post-transplantation had an HMR significantly higher than patients studied before 2 y post-transplantation (1.62 +/- 0.2 versus 1.34 +/- 0.2, P < 0.05). Myocardial MIBG uptake was anterolateral in 16 patients, anterior in 3 and anterolateral and septal in 3. Myocardial MIBG uptake was absent in 9 patients. Vasculopathy developed in 8 patients, and 5 of them (63%) had decreased myocardial MIBG uptake. Peak filling rate was higher in patients studied from 2 to 12 y post-transplantation (2.7 +/- 0.8 end-diastolic volume (EDV)/s versus 2.16 +/- 0.5 EDV/s, P = 0.02). CONCLUSION: Sympathetic reinnervation increases with time after heart transplantation and is seen more frequently after 2 y post-transplantation. Complete reinnervation of the transplanted heart does not occur even up to 12 y post-transplantation. Early vasculopathy may delay the process of sympathetic reinnervation.

Attenuated severity of new acute ischemic events in patients with previous coronary heart disease receiving long-acting nitrates.

BACKGROUND: Platelet aggregation and secondary vasoconstriction are key events in the genesis of acute coronary syndromes. HYPOTHESIS: Since nitrates have vasodilatory and antiaggregant effects, treatment with long-acting nitrates at the time of onset of acute coronary syndromes could be associated with attenuation of their severity. METHODS: A consecutive series of 533 patients with acute coronary syndrome and past history of coronary artery disease admitted to the Cardiology Service of a general hospital was studied. A specific questionnaire assessed the use of nitrates and other relevant drugs, as well as other clinical variables. The diagnosis of unstable angina or acute myocardial infarction (MI) was established according to clinical, electrocardiographic, and enzymatic criteria. RESULTS: In the whole cohort, 169 patients had MI and 364 had unstable angina. Previous use of long-acting nitrates was significantly more common in patients with unstable angina (56%) than in those with MI (37%) (p < 0.0001). Multivariate analysis identified being a nonsmoker [odds ratio: 95%, confidence limits (CL) 0.37, 0.23-0.59], previous unstable angina (CL 0.62, 0.41-0.92), use of aspirin (CL 0.58, 0.41-0.92), and use of long-acting nitrates (CL 0.61, 0.40-0.93) as the independent predictors of the development of unstable angina rather than MI; of these the combination of nitrates and aspirin was the strongest predictor. CONCLUSIONS: Long-acting nitrates as well as aspirin are suggested to have a protective or modifying effect on the development of acute coronary syndromes, favoring unstable angina rather than acute MI.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation.

OBJECTIVES: The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND: Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS: In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS: Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS: The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

[Patients with acute coronary syndrome: therapeutic approach (management patterns) and 1-year prognosis in a tertiary general hospital]. / Pacientes con síndrome coronario agudo: abordaje terapéutico (patrones de manejo) y pronóstico al año en un hospital general terciario.

BACKGROUND: To assess the determinants of short-term and one-year prognosis of all patients with suspected acute coronary syndrome seen by the cardiologist on duty in the Emergency Service of a tertiary hospital during a six month period. PATIENTS AND METHODS: 153 consecutive patients with a diagnosis of acute myocardial infarction, 225 with a diagnosis of unstable angina and 89 with a diagnosis of atypical chest pain were identified and their in-hospital characteristics and one-year prognosis were prospectively assessed. RESULTS: Age was higher than 65 years in 53% of acute myocardial infarction and in 54% of unstable angina patients. Only 3 patients were lost to follow-up. 35% of acute myocardial infarction patients had died or had reinfarction after one year and 16% of unstable angina patients had died or had suffered acute myocardial infarction. Baseline features, management patterns and prognosis of patients admitted with acute myocardial infarction to the Cardiology Service, to other hospital areas or to other hospitals were markedly different, and admission in areas other than the Cardiology Service was an independent mortality predictor. In unstable angina, complications happened in patients older than 75 years, those with previous revascularization procedures, those undergoing revascularization or those with lesions not deemed revascularizeable. CONCLUSIONS: a) In the study population there was a predominance of elderly patients; the proportion of patients with poor prognosis was considerably high; b) a sizeable proportion of patients with severe complications was scarcely represented in the major clinical trials; c) the possibility arises of a distribution of care resources tending to concentrate the greater therapeutic efforts in the patients with good prognosis.

Clinical outcome of severe asymptomatic chronic aortic regurgitation: a long-term prospective follow-up study.

One hundred one patients with asymptomatic chronic severe aortic regurgitation and normal ejection fraction were monitored for up to 10 years (mean 55.4 +/- 33.5 months). Predefined surgical indications were the development of cardiac symptoms or the documentation of impaired basal left ventricular function. During the follow-up period there were no cardiac deaths; 14 patients needed surgery, 8 because of development of symptoms and 6 because of left ventricular impairment. The risk of surgery was 12% at 5 years and 24% at 10 years. Baseline end-systolic diameter > 50 mm and radionuclide ejection fraction < 60% were independent predictors or either cardiac symptoms or left ventricular dysfunction. In patients needing surgery, a pattern of progressive left ventricular dilatation was demonstrated. There were no deaths during surgery, and echocardiographic and radionuclide parameters normalized in the first year of follow-up. Our data confirm that the prognosis of severe aortic regurgitation in patients with no symptoms is good and that the occurrence of asymptomatic left ventricular dysfunction is an uncommon event. Surgery can be safely postponed until the appearance of cardiac symptoms or the documentation of left ventricular dysfunction at rest.