Pregnancy after heart transplantation: a well-thought-out decision? The Quebec provincial experience - a multi-centre cohort study.

Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. We reviewed our provincial experience of pregnancy in HTx recipients by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long-term survival was compared to HTx recipient women of childbearing age who did not become pregnant. Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1 (2.6-27.0) years after HTx. Immunosuppression was CNI-based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4% vs. 5.5%), hypertension (38.5% vs. 4.6%), and diabetes (15.4% vs. 5.6%). Mean gestational age was 35.1 (23.4-39.6) weeks (72.2% live births; 53.8% prematurity). Mean birthweight was 2418 (660-3612) g. Serum creatinine increased during pregnancy, becoming significant after delivery (P = 0.0239), and returning to preconception level in all but three patients within a year. After 4.6 (1.2-17.2) years of follow-up, two rejection episodes occurred in one patient. Long-term mortality was similar to overall HTx women (Kaplan-Meier; P = 0.8071). Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival.

Generation of priority research questions to inform conservation policy and management at a national level.

Integrating knowledge from across the natural and social sciences is necessary to effectively address societal tradeoffs between human use of biological diversity and its preservation. Collaborative processes can change the ways decision makers think about scientific evidence, enhance levels of mutual trust and credibility, and advance the conservation policy discourse. Canada has responsibility for a large fraction of some major ecosystems, such as boreal forests, Arctic tundra, wetlands, and temperate and Arctic oceans. Stressors to biological diversity within these ecosystems arise from activities of the country's resource-based economy, as well as external drivers of environmental change. Effective management is complicated by incongruence between ecological and political boundaries and conflicting perspectives on social and economic goals. Many knowledge gaps about stressors and their management might be reduced through targeted, timely research. We identify 40 questions that, if addressed or answered, would advance research that has a high probability of supporting development of effective policies and management strategies for species, ecosystems, and ecological processes in Canada. A total of 396 candidate questions drawn from natural and social science disciplines were contributed by individuals with diverse organizational affiliations. These were collaboratively winnowed to 40 by our team of collaborators. The questions emphasize understanding ecosystems, the effects and mitigation of climate change, coordinating governance and management efforts across multiple jurisdictions, and examining relations between conservation policy and the social and economic well-being of Aboriginal peoples. The questions we identified provide potential links between evidence from the conservation sciences and formulation of policies for conservation and resource management. Our collaborative process of communication and engagement between scientists and decision makers for generating and prioritizing research questions at a national level could be a model for similar efforts beyond Canada.

Recurrent Cardiovascular Events in Survivors of Myocardial Infarction With ST-Segment Elevation (from the AMI-QUEBEC Study).

The characteristics and predictors of long-term recurrent ischemic cardiovascular events (RICEs) after myocardial infarction with ST-segment elevation (STEMI) have not yet been clarified. We aimed to characterize the 10-year incidence, types, and predictors of RICE. We obtained 10-year follow-up of STEMI survivors at 17 Quebec hospitals in Canada (the AMI-QUEBEC Study) in 2003. There were 858 patients; mean age was 60 years and 73% were male. The majority of patients receive reperfusion therapy; 53.3% and 39.2% of patients received primary percutaneous coronary intervention (PCI) and fibrinolytic therapy, respectively. Seventy-five percent of patients underwent in-hospital PCI (elective, rescue, and primary). At 10 years, 42% of patients suffered a RICE, with most RICEs (88%) caused by recurrent cardiac ischemia. The risk of RICE was the highest during the first year (23.5 per patient-year). At 10 years, the all-cause mortality was 19.3%, with 1/3 of deaths being RICE-related. Previous cardiovascular event, heart failure during the index STEMI hospitalization, discharge prescription of calcium blocker increased the risk of RICE by almost twofold. Each point increase in TIMI (Thrombolysis In Myocardial Infarction) score augmented the risk of RICE by 6%, whereas discharge prescription of dual antiplatelets reduced the risk of RICE by 23%. Our findings suggested that survivors of STEMI remain at high long-term risk of RICE despite high rate of reperfusion therapy and in-hospital PCI. Patients with previous cardiovascular event, in-hospital heart failure, and high TIMI score were particularly susceptible to RICE. Future studies are needed to confirm the impacts of calcium blocker and dual antiplatelets on long-term risk of RICE.

Hypertriglyceridemic waist: a useful screening phenotype in preventive cardiology?

The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles--the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Apolipoprotein-B, low-density lipoprotein cholesterol, and the long-term risk of coronary heart disease in men.

We examined whether plasma apolipoprotein-B (apo-B) levels add further information on the risk of coronary heart disease (CHD) after taking into account low-density lipoprotein (LDL) cholesterol concentrations and other traditional risk factors. Among 2,072 CHD-free men from the Québec Cardiovascular Study at entry and followed for 13 years, 230 had a first CHD event (CHD death or nonfatal myocardial infarction). Increased apo-B (tertile 1 vs 3) levels were associated with a significant increased risk of CHD after adjustment for nonlipid and lipid risk factors other than LDL cholesterol levels (relative risk 1.89, 95% confidence interval 1.31 to 2.73). High plasma LDL cholesterol concentrations (tertile 1 vs 3) were also associated with an increased risk of CHD independently of nonlipid and lipid risk factors (relative risk 2.02, 95% confidence interval 1.44 to 2.84). However, apo-B levels modulated to a significant extent the risk of CHD associated with increased concentrations of LDL cholesterol (>/=4.3 mmol/L). For instance, among men with high LDL cholesterol levels, those with an apo-B level <128 mg/dl were not at increased risk for CHD (relative risk 1.53, 95% confidence interval 0.89 to 2.62). In contrast, high levels of apo-B and LDL cholesterol were associated with a significant twofold increased risk of CHD (p <0.001). Receiver-operating curve analysis also indicated that plasma apo-B levels improved the ability to discriminate incident CHD cases among patients with high LDL cholesterol levels compared with a model based on LDL cholesterol levels (p = 0.04). In conclusion, plasma apo-B levels modulated the risk of CHD associated with LDL cholesterol over a 13-year follow-up.

Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study.

OBJECTIVE: The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study. METHODS AND RESULTS: Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-C<255A, respectively) were estimated from polyacrylamide gradient gel electrophoresis of whole plasma in the cohort of 2072 men of the population-based Quebec Cardiovascular Study. All men were free of IHD at the baseline examination and followed-up for a period of 13 years, during which 262 first IHD events (coronary death, nonfatal myocardial infarction, and unstable angina pectoris) were recorded. Our study confirmed the strong and independent association between LDL-C<255A levels as a proxy of the small dense LDL phenotype and the risk of IHD in men, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07). CONCLUSIONS: These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

Delays to reperfusion therapy in acute ST-segment elevation myocardial infarction: results from the AMI-QUEBEC Study.

BACKGROUND: Through the AMI-QUEBEC Study we sought to describe delays to reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) and to identify factors associated with prolonged delays. METHODS: We reviewed the charts of all consecutive patients with STEMI admitted to 17 hospitals in the province of Quebec in 2003 to obtain data on the time from presentation to reperfusion therapy. Data were available for 1189 (83.0%) of 1432 patients. RESULTS: The median delay to reperfusion therapy was 32 minutes (first and third quartile [Q1, Q3] 20, 49) for 535 patients who received fibrinolytic therapy, 109 minutes (Q1, Q3 79, 150) for 455 patients who underwent primary percutaneous coronary intervention (PCI) at the initial hospital of presentation and 142 minutes (Q1, Q3 115, 194) for 199 patients who underwent primary PCI after an interhospital transfer. Patients who presented outside daytime working hours, those who received primary PCI and those who required interhospital transfer for primary PCI were less likely to receive reperfusion therapy within current recommended times (odds ratios [ORs] 0.49, 0.56 and 0.15, respectively). Increased age was associated with prolonged delays only among patients who received fibrinolytic therapy (OR for each 10-year increase in age 0.95, 95% credible interval [CrI] 0.93-0.99 for fibrinolytic therapy and 0.99, 95% CrI 0.95-1.05, for primary PCI). INTERPRETATION: In 2003, many patients with STEMI in Quebec were not treated within the recommended times. Delays may be reduced by reorganizing pre-and in-hospital care for patients with STEMI to expedite delivery of reperfusion therapy.

Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study.

We tested the hypothesis that elevated plasma interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen concentrations are independent risk factors and interact in increasing the long-term risk of ischemic heart disease (IHD) in men. A total of 1982 IHD-free men from the Quebec Cardiovascular Study were followed over a period of 13 years during which 210 first fatal IHD events and non-fatal myocardial infarctions were recorded. Increased CRP levels (4th versus 1st quartile) were not associated with an increased risk of IHD after adjustment for non-lipid risk factors (age, body mass index, systolic blood pressure, diabetes, smoking and medication use at baseline), lipid risk factors (LDL and HDL cholesterol and triglyceride levels) and for IL-6 and fibrinogen (RR=0.70, 95% CI=0.43-1.13). High plasma IL-6 levels (4th versus 1st quartile) were associated with a 70% greater risk of IHD independent of confounding risk factors and of the other 2 inflammatory markers (RR=1.71, 95% CI=1.07-2.75). The relationship between high fibrinogen levels (4th versus 1st quartile) and IHD risk was borderline significant in multivariate analyses (RR=1.53, 95% CI=0.97-2.43). An inflammation score based on plasma IL-6 and fibrinogen levels improved the IHD risk predictive value of a multivariate model of traditional risk factors (p=0.03). Including plasma CRP levels into the inflammatory score provided no additional predictive value. In conclusion, elevated plasma IL-6 concentrations are more strongly related to IHD risk than CRP and fibrinogen. An inflammation score based on high plasma IL-6 and fibrinogen levels used in combination with traditional risk factors may improve our ability to adequately identify high risk individuals.

Insulin resistance syndrome, body mass index and the risk of ischemic heart disease.

BACKGROUND: Many people who are not obese according to standard height and weight criteria may still display features of insulin resistance syndrome and thus be at high risk of ischemic heart disease. We sought to investigate the effect of cumulative features of insulin resistance syndrome on the risk of ischemic heart disease associated with variations in body mass index (BMI) among men who participated in the Quebec Cardiovascular Study. METHODS: A cohort of 1824 nondiabetic men free of ischemic heart disease was evaluated at the 1985 baseline evaluation and followed for a period of 13 years, during which 284 first ischemic heart disease events were recorded. Relative hazards (RHs) of ischemic heart disease in 3 BMI groups (normal weight, overweight and obese) were estimated using Cox proportional hazards regression. RESULTS: Although obese men (BMI > or = 30 kg/m2) were the most likely to accumulate features of insulin resistance syndrome, the univariate risk of ischemic heart disease in this group was not significantly increased compared with normal-weight men (BMI < 25 kg/m2) (RH 1.26, 95% confidence interval [CI] 0.88-1.80). However, obese men who accumulated more than 4 features of insulin resistance syndrome were at increased risk of ischemic heart disease (RH 1.81, 95% CI 1.02-3.19) compared with normal-weight men who had fewer than 3 features of the syndrome. Conversely, having more than 4 features of insulin resistance syndrome was associated with a 3-fold increase in the risk of ischemic heart disease among normal-weight men (RH 3.01, 95% CI 1.70-5.32). INTERPRETATION: Although obesity is an important risk factor for ischemic heart disease, variations in BMI alone poorly reflect the risk of ischemic heart disease associated with features of insulin resistance syndrome.

Does correction of the friedewald formula using lipoprotein(a) change our estimation of ischemic heart disease risk? The Quebec Cardiovascular Study.

BACKGROUND: LDL-cholesterol is usually calculated using the Friedewald formula. This calculation method does not take into account the presence of Lp(a), which is associated with LDL-cholesterol. Dahlen has suggested that the Friedewald formula should be modified to account for Lp(a) associated cholesterol. This study was undertaken to determine if correction of the Friedewald formula would result in a better evaluation of ischemic heart disease (IHD) risk. METHODS: 2222 men free from IHD were prospectively followed for 5 years for the appearance of myocardial infarction, coronary insufficiency or coronary death. At the baseline evaluation all had a complete fasting lipid profile which included Lp(a) determinations. LDL-cholesterol levels were calculated from total cholesterol, total triglycerides and HDL-cholesterol using the Friedewald formula and also using the Dahlen modification of the Friedewald formula. RESULTS: During the follow-up there were 89 first IHD events. Both types of LDL-cholesterol calculations showed that the last tertile of the LDL-cholesterol distribution in comparison to the first tertile, doubles the relative risk (RR: 2.15; 95% confidence limits: 1.23-3.75) using the Friedewald formula (RR: 2.18; 95% confidence limits: 1.25-3.81) using the Dahlen modification. Lp(a) levels were not an independent predictor of IHD risk. CONCLUSION: Modification of the Friedewald formula to account for Lp(a) levels does not improve our evaluation of IHD risk.

Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Québec Cardiovascular Study.

Insulin resistance, through numerous related disturbances in glucose and lipoprotein-lipid metabolism, is associated with an increased risk of ischemic heart disease (IHD). The purpose of the present study was to examine the relationship between increased plasma free fatty acid (FFA) concentrations, as a feature of the insulin resistance syndrome, and the risk of IHD in men. Analyses were carried out in a nested, case-control sample of men selected from a population of 2103 individuals without IHD at baseline among whom 114 developed IHD during a 5-year follow-up period. Incident IHD cases were matched with controls for age, body mass index, smoking habits and alcohol intake. Analyses were performed while excluding (88 cases and 98 controls) and including (103 cases and 99 controls) patients with type 2 diabetes. Among non-diabetic individuals, elevated plasma FFA concentrations (3rd tertile of the distribution) yielded a twofold increase in the risk of IHD (odds ratio [OR] 2.1, P=0.05) compared with lower plasma FFA levels (lowest tertile) after adjusting for non-lipid risk factors. Further adjustment for insulin, triglycerides, apolipoprotein B, HDL cholesterol and small dense LDL attenuated significantly the relationship between plasma FFA concentrations and the risk of IHD. High plasma FFA levels showed no synergism with selected features of the insulin resistance syndrome in determining the risk of IHD. Inclusion of diabetic subjects in the study did not improve FFA independent prognostic value to the risk of IHD. These results suggest that elevated plasma FFA concentrations are associated with an increased risk of IHD. However, a single fasting measurement of plasma FFA levels does not appear to improve our ability to predict IHD onset in men when information on other risk factors is considered.

The impact of brain death on survival after heart transplantation: time is of the essence.

BACKGROUND: It has been suggested that the modality of brain death and time from brain death until harvest impact survival and rejection after heart transplantation. METHODS: Donor files from 475 adult heart-transplant recipients were examined. From these files, a total management time (time from incident leading to brain death until aortic cross clamp) was determined, and the cause of brain death was noted. Recipient characteristics, details of postoperative course, as well as survival were obtained from the Stanford University Medical Center Heart Transplantation Database. RESULTS: Two hundred and thirty (48.4%) donors sustained traumatic injuries, 112 (23.6%) suffered a subarachnoid hemorrhage, and 102 (21.4%) died of a gunshot wound to the head. The modality of brain death did not influence medium and long-term survival. A management time longer than 72 hours was associated with poorer outcome of the heart-transplant recipients. There were significantly more treated rejection episodes in recipients whose donor sustained traumatic injuries. CONCLUSION: Modality of brain death does not impact survival but appears to influence rejection. Increased management time is associated with adverse survival trends in heart-transplant recipients.

Association of fibrinogen and lipoprotein(a) as a coronary heart disease risk factor in men (The Quebec Cardiovascular Study).

Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented. Men with CHD were older, smoked more, had a higher prevalence of diabetes, and higher levels of systolic blood pressure, cholesterol, low-density lipoprotein cholesterol, Lp(a), and fibrinogen, and lower plasma high-density lipoprotein cholesterol levels. Only fibrinogen levels in the upper tertile of the distribution compared with the lower tertiles were associated with a significant risk of CHD (adjusted risk ratio 2.5; 95% confidence interval [CI] 1.4 to 4.2; p = 0.0010). Such an association was not observed with Lp(a). To assess a possible relation between fibrinogen and Lp(a) to the risk of CHD events, men were assigned to 1 of 4 groups according to fibrinogen median levels and a Lp(a) cut-off level of 300 mg/L: group 1: fibrinogen < 4.05 g/L and Lp(a) < 300 mg/L; group 2: fibrinogen < 4.05 g/L and Lp(a) > or =300 mg/L; group 3: fibrinogen > or =4.05 g/L and Lp(a) < 300 mg/L; and group 4: fibrinogen > or =4.05 g/L and Lp(a) > or =300 mg/L. Using group 1 as a reference, a significant risk ratio was only documented in group 4 (2.5; 95% CI 1.2 to 5.1; p = 0.0132). In this population, high fibrinogen levels associated with high Lp(a) levels significantly increased the risk of CHD.

Effect of plasma C-reactive protein levels in modulating the risk of coronary heart disease associated with small, dense, low-density lipoproteins in men (The Quebec Cardiovascular Study).

This purpose of this study was to investigate how plasma C-reactive protein (CRP), a nonspecific acute-phase reactant, modulates the risk of coronary heart disease (CHD) associated with the small, dense, low-density lipoprotein (LDL) phenotype. LDL particle size and plasma CRP were measured in the Quebec Cardiovascular Study cohort of 2,025 men free of CHD at baseline, among whom 103 had a first CHD event during a 5-year follow-up period. Plasma CRP levels were measured using the Behring Latex-Enhanced (highly sensitive) CRP assay. LDL particle size phenotype was characterized using 2% to 16% polyacrylamide gradient gel electrophoresis. There were weak but significant associations between plasma CRP levels and features of LDL size, such as the proportion of LDL with a diameter <255 A (r = 0.09, p <0.001) and LDL peak particle size (r = -0.09, p <0.001). Variations in plasma CRP levels modulated the risk of CHD associated with small LDL peak particle size (relative risk 4.3 vs 2.5 in men with high vs low plasma CRP levels, respectively) and with an elevated proportion of LDL <255 A (relative risk 6.6 vs 3.0). Thus, increased plasma CRP levels further elevate the risk of CHD associated with having small, dense LDL particles.

Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk.

The objective of the present study was to examine concordance/discordance among 4 atherogenic indexes of cardiovascular risk: plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, and apolipoprotein B-100 (apoB). Analyses were conducted in a cohort of 2,103 men without coronary artery disease (CAD) at the onset of the Quebec Cardiovascular Study. Although there were strong and highly significant correlations among the 4 risk indexes (0.78 < r < 0.97), only 50% of all subjects had concordant apoB and LDL cholesterol levels (i.e., values that fell into the same quintile of the population distribution). Moreover, concordance/discordance was not the same throughout the range of both variables; it was greater at the extremes of their respective distributions (65%), but significantly less in the midpoints (<40%). ApoB appeared to be more concordant with non-HDL cholesterol than with LDL cholesterol, although >1/3 of all subjects had discordant levels. Kappa analysis confirmed that there was only fair agreement between apoB and total or LDL cholesterol (0.38 and 0.36, respectively) and only moderate agreement between non-HDL cholesterol and apoB (0.47). Finally, a significant proportion of subjects (528 of 2,103) who had disproportionately higher apoB levels than would have been predicted based on their LDL cholesterol concentrations was more obese and manifested several features of the metabolic syndrome. They also had a significantly increased cardiovascular risk. In summary, plasma apoB and the various cholesterol indexes are complementary rather than competitive indexes of atherosclerotic risk and provide further evidence as to why measurement of apoB should be part of a standard lipoprotein assessment of CAD risk.

Reversal of diabetes-induced rat graft transplant coronary artery disease by metformin.

BACKGROUND: Induction of diabetes in rat heterotopic heart transplantation models leads to an accelerated form of severe transplant coronary artery disease (TxCAD). We undertook this study to determine whether treatment of diabetes with metformin would favorably affect TxCAD. METHODS: Heterotopic abdominal heart transplantation was performed in rat isograft and allograft models. After transplantation, diabetes was induced with streptozotocin. Fifty percent of the animals received metformin at 500 mg/kg twice daily. We quantitatively assessed TxCAD using histologic sections of harvested hearts at 30 and 60 days with computer-assisted morphometry. We compared vessels in the first tertile of the area distribution with vessels in the last tertile. RESULTS: Fasting glucose levels in metformin-treated animals were 161 +/- 45 mg/dl compared with 400 +/- 120 mg/dl (p < 0.05) in untreated rats. Treatment with metformin led to decreased diabetes-induced TxCAD in the larger vessels. This effect was sustained during the study course in the isografts but not in the allografts. Treatment with metformin did not prevent progression of TxCAD in the smaller vessels at 60 days. CONCLUSIONS: Metformin reduced luminal occlusion and severe TxCAD in the larger vessels but did not alter the course of TxCAD in the smaller vessels. These results may have therapeutic implications for patients.

Post-operative conversion from cyclosporine to tacrolimus in heart transplantation: a single-center experience.

BACKGROUND: Tacrolimus is a potent calcineurin inhibitor that was introduced to heart transplantation in the early 1990s. The side-effect profile of tacrolimus is more favorable than that of cyclosporine and some reports have suggested an advantage of tacrolimus in the treatment of rejection. The present study was undertaken to determine whether a late conversion to tacrolimus affords these benefits to heart transplant recipients. METHODS: Charts from 109 patients who underwent conversion from cyclosporine to tacrolimus for recurrent rejection or adverse effects were retrospectively reviewed. RESULTS: During the year after conversion to tacrolimus, there was a significant decrease in treated rejection episodes. Conversion to tacrolimus rapidly resulted in an improved lipid profile. Two years after conversion blood pressure was significantly reduced. Apart from rejection, these benefits were found mainly among individuals converted to tacrolimus within 1 year of heart transplantation. CONCLUSIONS: Conversion from cyclosporine to tacrolimus is safe and results in a more favorable risk factor profile. However, most of the benefits are seen in individuals converted within 1 year of transplantation.

Preferential involvement of larger vessels in a rat model of diabetes-induced graft vasculopathy.

Using previously described models of diabetes-induced transplant coronary artery atherosclerosis (TxCAD), we quantitatively assessed TxCAD using computer-assisted morphometric measurements. More than 95% of the evaluated vessels were intramyocardial vessels. The first and last tertile of the vessel size distribution were evaluated for the presence of TxCAD. Severe TxCAD, defined as a luminal occlusion > or =75%, was more prevalent in the larger vessels. We observed a differential involvement based on vessel size in diabetes-induced TxCAD.

Cardiac allograft vasculopathy by intravascular ultrasound in heart transplant patients: substudy from the Everolimus versus mycophenolate mofetil randomized, multicenter trial.

OBJECTIVES: A pre-planned substudy of a larger multicenter randomized 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 standard-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 randomized, multicenter trial who underwent heart transplantation and were randomized 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 subpopulations. CV surgery: transplantation, ventricular assistance, cardiomyopathy.