Patients with end stage renal failure (ESRF) have an increased risk of premature cardiovascular disease. Left ventricular (LV) abnormalities, so called 'uremic cardiomyopathy', are associated with poorer outcome. Cardiac magnetic resonance imaging (CMR) accurately defines LV dimensions and identifies underlying myocardial pathology. We studied the relationship between LV function and myocardial pathology in ESRF patients with CMR. A total of 134 patients with ESRF underwent CMR. LV function was assessed with further images acquired after gadolinium-diethylentriaminepentaacetic acid (DTPA). The presence of myocardial fibrosis was indicated by late gadolinium enhancement (LGE). Two main myocardial pathologies were identified. A total of 19 patients (14.2%) displayed 'subendocardial LGE' representing myocardial infarction, which was associated with conventional cardiovascular risk factors including a history of ischemic heart disease (IHD) (P < 0.001), hypercholesterolemia (P < 0.05), and diabetes (P < 0.01). Patients with subendocardial LGE had greater LV mass (P < 0.05), LV dilation (P < 0.01), and LV systolic dysfunction (P < 0.001) compared to patients with no evidence of LGE. The second pattern, 'diffuse LGE', seen in 19 patients (14.2%) appeared to represent regional areas of diffuse myocardial fibrosis. Diffuse LGE was associated with greater LV mass compared to patients without LGE (P < 0.01) but not systolic dysfunction. In total, 28.4% of all patients exhibited evidence of myocardial fibrosis demonstrated by LGE. In contrast to published literature describing three forms of uremic cardiomyopathy - left ventricular hypertrophy (LVH), dilation, and systolic dysfunction, we have shown that LVH is the predominant cardiomyopathy specific to uremia, while LV dilation and systolic dysfunction are due to underlying (possibly silent) ischemic heart disease.

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end-stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twentytwo patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow-up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 ± 0.6 years vs. listed not transplanted 4.1 ± 1.4 years vs. not listed 3.1 ± 1.7 years; p < 0.001). Ninety-nine patients underwent coronary angiography; 65 had normal or lowgrade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.

Background and objectives: Patients with end-stage renal failure (ESRD) have an increased risk of premature cardiovascular (CV) disease. Left ventricular hypertrophy is an independent risk factor for CV events and death in ESRD. Renal transplantation has been associated with reduction in CV risk and echocardiographic regression of left ventricular hypertrophy. However, echocardiography overestimates LV mass in ESRD patients. Cardiac magnetic resonance (CMR) provides more detailed, volume-independent, measures of cardiac structure. Changes in LV mass measured by CMR after renal transplantation were studied.Design, setting, participants, & measurements: Fifty patients underwent CMR on two occasions. Twenty-five were transplanted before the second scan. CMR was performed to measure LV mass index (LVMI), ejection fraction, end-diastolic and end-systolic volumes. Changes were expressed as percentage change over time. Patients with CV events between scans (e.g., acute coronary syndrome, myocardial infarction) were excluded. All transplant patients had serum creatinine <150 mol/L.Results: There was no significant change in LVMI between patients who underwent renal transplantation and those who remained on dialysis (transplanted mean, 2.75%/yr, ؎ 9.1 versus dialysis, ؊3.6%/yr ؎ 16.7). In addition, there were no significant changes in end-diastolic volume (transplant, 0.1%/yr ؎ 19.5 versus not transplanted, ؊3.4%/yr ؎ 31.5), end-systolic volume (transplanted mean, 15.2%/yr ؎ 65.2 versus not transplanted, 3.0%/yr ؎ 55.5), or ejection fraction (transplant, 2.1%/yr ؎ 11.9 versus not transplanted, ؊0.4%/yr ؎ 5.3).Conclusions: Renal transplantation is not associated with significant regression of LVMI on CMR compared with patients who remain on the transplant waiting list.

Key PointsQuestionIs transcatheter aortic valve implantation (TAVI) noninferior to surgical aortic valve replacement (surgery) in patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk?FindingsIn this randomized clinical trial that included 913 patients at moderately increased operative risk due to age or comorbidity, all-cause mortality at 1 year was 4.6% with TAVI vs 6.6% with surgery, a difference that met the prespecified noninferiority margin of 5%.MeaningAmong patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, treatment with TAVI was noninferior to surgery with respect to all-cause mortality at 1 year.

Cardiovascular disease is the principal cause of mortality in patients with renal failure. Left ventricular (LV) abnormalities are adverse prognostic indicators for cardiovascular outcome. The aim of this study was to use cardiac magnetic resonance scanning (CMR) to define LV functional abnormalities in haemodialysis (HD) patients and clarify the determinants of blood pressure (BP) and the effect of anaemia in this population. We studied 44 HD patients and 11 controls with CMR performed following dialysis. Forty patients and 11 controls completed the study. LV mass (P<0.001) and estimated systemic vascular resistance (SVR) (P = 0.002) were significantly higher in the dialysis group compared to controls. LV ejection fraction (P = 0.002) and SV (P = 0.043) were lower than controls. In the HD patients, BP correlated significantly with cardiac output (CO; r = 0.569, P<0.001) and end diastolic volume (EDV; r = 0.565, P<0.001) but there was no correlation between BP and SVR (r = 0.201, P = 0.594). Haemoglobin was inversely correlated with both CO (r = -0.531, P<0.001) and EDV (r = -0.493, P = 0.001) and positively with SVR (r = 0.402, P = 0.009). HD patients had a higher LV mass and lower ejection fraction than controls. The relationship of BP with CO, but not SVR, supports the theory that a major determinant of BP is intravascular volume and CO rather than vascular resistance although there was a fixed increase in SVR in this population. Improved understanding of the mechanisms underlying increased SVR and improved control of CO and intravascular volume may allow better therapeutic strategies. CMR provides insights into the pathophysiology of hypertension and LV dysfunction in HD patients.

1. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) reduce serum cholesterol and have proven benefits in the treatment of cardiovascular disease. However, recent work suggests that statins may exert immunosuppressive effects in isolated lymphocytes and in solid organ transplant recipients. Fluvastatin does not interfere with the metabolism of commonly used immunosuppressive agents and, therefore, may have benefits in transplant recipients. 2. The aim of the present study was to investigate the potential immunomodulatory effects of fluvastatin in vitro in human lymphocytes and the underlying effects on signal transduction. 3. In vitro, fluvastatin (10 micromol/L) caused a time-dependent inhibition of T cell proliferation in response to cross-linking of CD3. 4. Thymidine incorporation was reduced by 22, 81 and 92% at days 1, 3 and 5, respectively. 5. Mevalonate (1 micromol/L) treatment for 4 or 24 h significantly reduced the inhibitory effects of fluvastatin; the reversal was abrogated by simultaneous exposure to mevalonate and a farnesyl transferase inhibitor. 6. At a subcellular level, fluvastatin treatment was associated with reduced functional activity of Ras-dependent extracellular signal-regulated kinase pathways and of Rho-dependent p38 activation. 7. These data suggest that the potential immunosuppressive actions of statins involve inhibition of subcellular pathways dependent on isoprenylation of signal peptides, including Ras, Rho and related G-proteins.

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Complex atrial anatomy continues to challenge transcatheter device closure of septal defects. Devices and technology continue to evolve. We report three cases from our institution where the new Gore Septal Occluder was utilized for the closure of a lateral tunnel fenestration, a moderate-sized secundum atrial septal defect and a long tunnel patent foramen ovale. Each case highlights the successful use of this new generation device in challenging circumstances.