Left Atrial Glucose Metabolism Evaluation by 18F-FDG-PET in Persistent Atrial Fibrillation and in Sinus Rhythm.

The role of atrial metabolism alterations for initiation and atrial fibrillation (AF) persistence remains poorly understood. Therefore, we evaluated left atrial glucose metabolism by nicotinic acid derivative stimulated 18-fluorodeoxyglucose positron emission tomography in 36 patients with persistent AF undergoing catheter ablation before and 3 months after return to sinus rhythm and compared values against healthy controls. Under identical hemodynamics and metabolic conditions, and although left ventricular FDG uptake remained unchanged, patients in persistent AF presented significantly higher total left atrial and left atrial appendage uptake, which decreased significantly after return to sinus rhythm, despite improvement of passive and active atrial contractile function. These findings support a role of altered glucose metabolism and metabolic wasting underlying the pathophysiology of persistent AF.

The CECARI Study: Everolimus (Certican®) Initiation and Calcineurin Inhibitor Withdrawal in Maintenance Heart Transplant Recipients with Renal Insufficiency: A Multicenter, Randomized Trial.

In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30-60 mL/min/1.73 m2) were randomized to start everolimus with CNI withdrawal (N = 29) or continue their current CNI-based immunosuppression (N = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.18). In the on-treatment analysis, the difference did reach statistical significance (+9.4 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.047). The composite safety endpoint of all-cause mortality, major adverse cardiovascular events, or treated acute rejection was not different between groups. Nonfatal adverse events occurred in 96.6% of patients in the everolimus group and 57.1% in the CNI group (p < 0.001). Ten patients (34.5%) in the everolimus group discontinued the study drug during follow-up due to adverse events. The poor adherence to the everolimus therapy might have masked a potential benefit of CNI withdrawal on renal function.

What is the potential increase in the heart graft pool by cardiac donation after circulatory death?

Heart transplantation remains the only definite treatment option for end-stage heart diseases. The use of hearts procured after donation after circulatory death (DCD) could help decrease the heart graft shortage. The aim of this study was to evaluate the potential increase in heart graft pool by developing DCD heart transplantation. We retrospectively reviewed our local donor database from 2006 to 2011, and screened the complete controlled DCD donor population for potential heart donors, using the same criteria as for donation after brain death (DBD) heart transplantation. Acceptable donation warm ischemic time (DWIT) was limited to 30 min. During this period 177 DBD and 70 DCD were performed. From the 177 DBD, a total of 70 (39.5%) hearts were procured and transplanted. Of the 70 DCD, eight (11%) donors fulfilled the criteria for heart procurement with a DWIT of under 30 min. Within the same period, 82 patients were newly listed for heart transplantation, of which 53 were transplanted, 20 died or were unlisted, and 9 were waiting. It could be estimated that 11% of the DCD might be heart donors, representing a 15% increase in heart transplant activity, as well as potential reduction in the deaths on the waiting list by 40%.

Myocardial contractile reserve during exercise predicts left ventricular reverse remodelling after cardiac resynchronization therapy.

AIMS: Lack of response to cardiac resynchronization therapy (CRT) may be due to the presence of significant amount of scar or fibrotic tissue at myocardial level. This study sought to investigate the potential impact of myocardial contractile reserve as assessed during exercise echocardiography on left ventricular (LV) reverse remodelling (decrease in LV end-systolic volume > or =15% after 6 months of CRT). METHODS AND RESULTS: Fifty-one consecutive patients with heart failure underwent exercise Doppler echocardiography before CRT implantation to assess global contractile reserve and local contractile reserve (assessed by two-dimensional speckle tracking) in the region of the LV pacing lead. Responders (30 patients) showed a greater exercise-induced increase in left ventricular ejection fraction (LVEF) compared with non-responders (P < 0.001). Contractile reserve was directly related to the improvement in LVEF and to LV reverse remodelling after 6 months of CRT (P < 0.001). A 6.5% exercise-induced increase in LVEF yielded a sensitivity of 90% and a specificity of 85.7% to predict the response after 6 months of CRT. Baseline myocardial deformation as well as contractile reserve in the LV pacing lead region was greater in responders than in non-responders (P < 0.0001). CONCLUSION: Myocardial contractile reserve (global and regional) is a strong predictive factor of LV reverse remodelling after CRT.

Impact of contractile reserve on acute response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) provides benefit for congestive heart failure, but still 30% of patients failed to respond to such therapy. This lack of response may be due to the presence of significant amount of scar or fibrotic tissue at myocardial level. This study sought to investigate the potential impact of myocardial contractile reserve as assessed during exercise echocardiography on acute response following CRT implantation. METHODS: Fifty-one consecutive patients with heart failure (LV ejection fraction 27% +/- 5%, 67% ischemic cardiomyopathy) underwent exercise Doppler echocardiography before CRT implantation to assess global contractile reserve (improvement in LV ejection fraction) and local contractile reserve in the region of the LV pacing lead (assessed by radial strain using speckle tracking analysis). Responders were defined by an increase in stroke volume > or = 15% after CRT. RESULTS: Compared with nonresponders, responders (25 patients) showed a greater exercise-induced increase in LV ejection fraction, a higher degree of mitral regurgitation and a significant extent of LV dyssynchrony. The presence of contractile reserve was directly related to the acute increase in stroke volume (r = 0.48, p < 0.001). Baseline myocardial deformation as well as contractile reserve in the LV pacing lead region was greater in responders during exercise than in nonresponders (p < 0.0001). CONCLUSION: The present study showed that response to CRT largely depends not only on the extent of LV dyssynchrony and the severity of mitral regurgitation but also on the presence of contractile reserve.

Is cystatin C useful for the detection and the estimation of low glomerular filtration rate in heart transplant patients?

Although previously studied in patients with chronic kidney disease, there is less data for the use of cystatin C and cystatin C-based formulas in heart transplant recipients. The ability of creatinine and cystatin C to detect renal failure (glomerular filtration rate [GFR] below 60 mL/min/1.73 m(2)) in heart transplant patients has been compared. The accuracy and precision of a creatinine-based formula (Modification of Diet in Renal Disease [MDRD]) versus a cystatin C-based formula (Rule's formula) to estimate GFR have also been studied. GFR was measured using the (51)Cr-ethylenediamine tetraacetic acid tracer in 27 patients. There was no significant difference between GFR and the reciprocal of creatinine or cystatin C. Receiver operating characteristic curves for cystatin C and creatinine were similar. Both formulas were well correlated with the GFR. The bias of the cystatin C-based was significantly better than one of the MDRD formula, but the standard deviation appeared better for the MDRD formula (bias of +3.9 mL/min/1.73 m(2) versus +12 mL/min/1.73 m(2) and SD of 8.5 versus 11.6, respectively). Plasma cystatin C has no clear advantage over serum creatinine to detect renal failure in heart transplanted patients.

Creatinine-based formulae for the estimation of glomerular filtration rate in heart transplant recipients.

Chronic renal failure (CRF) is a common complication in heart transplant patients. Serum creatinine has clear limitations for the detection and estimation of glomerular filtration rate (GFR). Various creatinine-based formulae are classically used for GFR estimation, but little scientific evidence exists for such use in a heart transplant population. GFR was measured using the plasmatic clearance of the glomerular tracer (51)Cr-EDTA in 27 heart transplant patients with two measures for 22 of the patients. Forty-nine measures were thus available for analysis. The precision and accuracy (Bland and Altman analysis) of the Cockcroft, simplified Modified Diet in Renal Diseases (MDRD) and new Mayo Clinic formulae were compared. The mean GFR of the population was 39 +/- 15 mL/min/1.73 m(2). All formulae were well correlated with the GFR. With the Bland and Altman analysis, the accuracy of the MDRD formula appeared higher than that of the Cockcroft or the Mayo Clinic formulae (bias of +12 mL/min/1.73 m(2), vs. +19.9 mL/min/1.73 m(2), and +22.1 mL/min/1.73 m(2), respectively). The difference between the estimated and measured GFR was higher than 20 mL/min/1.73 m(2) in 51% and 55% cases when using the Cockcroft and the Mayo Clinic formulae respectively, whereas the difference was only noted in 14% cases when the MDRD was used. Among creatinine-based formulae, the MDRD appears the most precise and accurate for estimating the GFR in heart transplant patients. However, when the GFR must be measured with high accuracy, we recommend the use of a reference method like inulin or (51)Cr-EDTA plasma clearance techniques.