Recovery of circadian melatonin rhythm after a melatonin holiday in daytime haemodialysis patients on long-term exogenous melatonin.

The effects of exogenous melatonin on sleep diminish after its long-term use in haemodialysis patients. Our aim was to determine whether melatonin levels accumulate after chronic (at least three months) use of exogenous melatonin, 5 mg daily, and whether discontinuation of this treatment improves endogenous melatonin production and improves the circadian sleep-wake rhythm. In this case series, stable haemodialysis patients discontinued their chronic exogenous melatonin usage for seven days and melatonin concentrations in saliva were analysed. The primary endpoint was recovery of a normal circadian melatonin rhythm. Secondary endpoints were the effects on melatonin pharmacokinetics and sleep parameters. At day three after discontinuation the normal circadian melatonin rhythm recovered in the two patients who discontinued the treatment for the full week. They also had an effective maximum trough level of melatonin. Discontinuing melatonin seems to result in recovery of the circadian rhythm, based on achievement of effective melatonin thresholds. Further research is necessary to investigate whether sleep parameters improve after a drug holiday.most appropriate treatment.

Longitudinal Strain Stress-Echo Evaluation of Aged Marginal Donor Hearts: Feasibility in the Adonhers Project.

BACKGROUND: The Adonhers (aged donor heart rescue by stress-echo protocol) Project was created to resolve the current shortage of donor hearts. One of the great limits of stress echo is the operator dependency. Speckle-tracking echocardiography (STE), offering a quantitative objective analysis of myocardial deformation, may help to overcome this limit. This study aimed to verify feasibility of a stress-strain echo analysis in selection of aged donor hearts for heart transplant. METHODS: From February 2014 to October 2015, 22 marginal candidate donors (16 men) ages 58 ± 4 years were initially enrolled. After legal declaration of brain death, all marginal donors underwent bedside echocardiography, with baseline and (when resting echocardiography was normal) dipyridamole (0.84 mg/kg in 6 minutes) stress echo. In all patients, left ventricular (LV) longitudinal myocardial deformation was obtained by STE in the 4-, 2-, and 3-chamber views, obtaining the average global longitudinal strain (GLS). GLS was assessed at baseline and at the peak of stress echo. RESULTS: Baseline echocardiography showed wall motion abnormalities in 9 patients (excluded from donation). Stress echocardiography was performed in the remaining 13 patients. Results were normal in 8, who were uneventfully transplanted in marginal recipients. Stress results were abnormal in 5 (excluded from donation). STE was obtained in all cases (100% feasibility) and ΔGLS was significantly different between normal and pathological stress-echo (+13.2 ± 5.2 versus -6.1% ± 3.1%, P = .0001, respectively). CONCLUSIONS: STE showed an excellent feasibility in analysis of LV myocardial longitudinal strain at baseline and at the peak of stress echo of marginal heart donors. Further experience is needed to confirm STE as a valuable additional mean to better interpret stress echo in marginal donors.

First Evidence of Cardiac Stem Cells From the Left Ventricular Apical Tip in Patients With Left Ventricular Assist Device Implantation.

BACKGROUND: Recent studies have challenged the dogma that the adult heart is a postmitotic organ and raise the possibility of the existence of resident cardiac stem cells (CSCs). Our study aimed to explore if these CSCs are present in the "ventricular tip" obtained during left ventricular assist device (LVAD) implantation from patients with end-stage heart failure (HF) and the relationship with LV dysfunctional area extent. METHODS: Four consecutive patients with ischemic cardiomyopathy and end-stage HF submitted to LVAD implantation were studied. The explanted "ventricular tip" was used as a sample of apical myocardial tissue for the pathological examination. Patients underwent clinical and echocardiographic examination, both standard transthoracic echocardiography (TTE) and speckle tracking echocardiography (STE), before LVAD implantation. RESULTS: All patients presented severe apical dysfunction, with apical akinesis/diskinesis and very low levels of apical longitudinal strain (-3.5 ± 2.9%). Despite this, the presence of CSCs was demonstrated in pathological myocardial samples of "ventricular tip" in all 4 of the patients. It was found to be a mean of 6 c-kit cells in 10 fields magnification 40×. CONCLUSIONS: Cardiac stem cells can be identified in the LV apical segment of patients who have undergone LVAD implantation despite LV apical fibrosis.

Evaluation of Right Ventricular Function in the Management of Patients Referred for Left Ventricular Assist Device Therapy.

BACKGROUND: Speckle tracking echocardiography analysis (STE) has recently allowed an in-depth analysis of right ventricular (RV) performance. The aim of the study was to observe RV function by STE in patients with advanced heart failure before and after left ventricular assist device (LVAD) implantation. METHODS: A transthoracic echocardiogram was performed in 19 patients referred for LVAD implant at baseline and with serial echocardiograms after LVAD implantation (Jarvik 2000). All echocardiographic images were analyzed off line by an independent operator to calculate with STE the RV free wall longitudinal strain (RVLS). RESULTS: All the patients, except 4, showed a progressive increase of RVLS after LVAD implant. However, 4 patients, who presented the lowest RVLS values at baseline, presented a further RV failure in the postoperative. The value of -11% represented the empirical preoperative cutoff able to identify patients at greater risk of postimplant RV failure. CONCLUSIONS: RV myocardial deformation may have important clinical implications for the selection and management of LVAD patients. It can be used to evaluate RV function before LVAD implantation, to drive decisional strategy regarding the management of this type of patients, and after LVAD implant for the follow-up.