Prognostic value of new left atrial volume index severity partition cutoffs after cardiac rehabilitation program in patients undergoing cardiac surgery

Background: Previous studies showed that left atrial enlargement is an independent marker of adverse outcomes in both primary and secondary cardiovascular prevention. However, no data are available on long-term outcomes in patients undergoing valve surgery and/or coronary artery by-pass graft (CABG) surgery. Aim of the study was to evaluate long-term prognostic role of left atrial volume index (LAVi) after cardiac surgery, using the cutoff values recently proposed by the European Association of Cardiovascular Imaging and American Society of Echocardiography. Methods: We created a retrospective registry of 1703 consecutive patients who underwent cardiovascular rehabilitation program after cardiac surgery, including CABG, valve surgery and valve + CABG surgery. LAVi was calculated as ratio of left atrium volume to body surface area, in ml/m2 at discharge; 563 patients with available LAVi data were included in the study. Results: In the whole population LAVi was 36 ± 14 ml/m2 (mean ± SD) and the follow-up time was 5 ± 1. 5 years. Increased LAVi (>34 ml/m2) predicted major adverse cardiovascular and cerebrovascular events (MACCEs) (HR = 2.1; CI95 %: 1.4–3.1; p < 0.001) and cardiovascular mortality (HR = 2.2; CI95 %: 1.0–4.5; p = 0.032). An increased LAVi remained MACCEs predictor after adjustement for age, gender, diabetes, atrial fibrillation at discharge, echocardiographic E/A ratio and left ventricular ejection fraction (HR = 1.8; CI95 %: 1.0–3.0; p = 0. 036). When the study population was split according to increasing LAVi values, left atrium enlargement resulted a predictor of progressively worse adverse outcome. Conclusions: LAVi is a predictor of long-term adverse cardiovascular outcome after cardiac surgery, even after correction for main clinical and echocardiographic variables. The recently recommended LAVi severity cutoffs appear adequate to effectively stratify outcome in patients undergoing rehabilitation after cardiac surgery

Red blood cell distribution width as a novel prognostic marker after myocardial revascularization or cardiac valve surgery

The red blood cell distribution width (RDW) measures the variability in the size of circulating erythrocytes. Previous studies suggested a powerful correlation between RDW obtained from a standard complete blood count and cardiovascular diseases in both primary and secondary cardiovascular prevention. The current study aimed to evaluate the prognostic role of RDW in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. The study included 1.031 patients with available RDW levels, prospectively followed for a mean of 4.5 +/- 3.5 years. The mean age was 68 +/- 12 years, the mean RDW was 14.7 +/- 1.8%; 492 patients (48%) underwent cardiac rehabilitation after myocardial revascularization, 371 (36%) after cardiac valve surgery, 102 (10%) after valve-plus-coronary artery by-pass graft surgery, 66 (6%) for other indications. Kaplan-Meier analysis and Cox hazard analysis were used to associate RDW with mortality. Kaplan-Meier analysis demonstrated worse survival curves free from overall (log-rank p&lt;0.0001) and cardiovascular (log-rank p&lt;0.0001) mortality in the highest RDW tertile. Cox analysis showed RDW levels correlated significantly with the probability of overall (HR 1.26; 95% CI 1.19-1.32; p&lt;0.001) and cardiovascular (HR 1.31; 95% CI 1.23-1.40; p&lt;0.001) mortality. After multiple adjustments for cardiovascular risk factors, hemoglobin, hematocrit, C-reactive protein, microalbuminuria, atrial fibrillation, glomerular filtration rate,left ventricular ejection fraction and number of exercise training sessions attended, the increased risk of overall (HR 1.10; 95% CI 1.01-1.27; p=0.039) and cardiovascular (HR 1.13; 95% CI 1.01-1.34; p=0.036)mortality with increasing RDW values remained significant. The RDW represents an independent predictor of overall and cardiovascular mortality in secondary cardiovascular prevention patients undergoing cardiac rehabilitation

The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment

Aims SPTLC1-related disorder is a late onset sensory-autonomic neuropathy associated with perturbed sphingolipid homeostasis which can be improved by supplementation with the serine palmitoyl-CoA transferase (SPT) substrate, l-serine. Recently, a juvenile form of motor neuron disease has been linked to SPTLC1 variants. Variants affecting the p.S331 residue of SPTLC1 cause a distinct phenotype, whose pathogenic basis has not been established. This study aims to define the neuropathological and biochemical consequences of the SPTLC1 p.S331 variant, and test response to l-serine in this specific genotype. Methods We report clinical and neurophysiological characterisation of two unrelated children carrying distinct p.S331 SPTLC1 variants. The neuropathology was investigated by analysis of sural nerve and skin innervation. To clarify the biochemical consequences of the p.S331 variant, we performed sphingolipidomic profiling of serum and skin fibroblasts. We also tested the effect of l-serine supplementation in skin fibroblasts of patients with p.S331 mutations. Results In both patients, we recognised an early onset phenotype with prevalent progressive motor neuron disease. Neuropathology showed severe damage to the sensory and autonomic systems. Sphingolipidomic analysis showed the coexistence of neurotoxic deoxy-sphingolipids with an excess of canonical products of the SPT enzyme. l-serine supplementation in patient fibroblasts reduced production of toxic 1-deoxysphingolipids but further increased the overproduction of sphingolipids. Conclusions Our findings suggest that p.S331 SPTLC1 variants lead to an overlap phenotype combining features of sensory and motor neuropathies, thus proposing a continuum in the spectrum of SPTLC1-related disorders. l-serine supplementation in these patients may be detrimental

In-hospital day-by-day systolic blood pressure variability during rehabilitation: a marker of adverse outcome in secondary prevention after myocardial revascularization

Objective: Although it is known that increased visit-to-visit or home day-by-day variability of blood pressure (BP), independently of its average value, results in an increased risk of cardiovascular events, the prognostic value of in-hospital day-by-day BP variability in secondary cardiovascular prevention has not yet been established. Methods: We studied 1440 consecutive cardiac patients during a cardiovascular rehabilitation program of about 12 days after coronary artery bypass graft (CABG) and/or valve surgery. We measured auscultatory BP at the patient bed in each rehabilitation day twice, in the morning and the afternoon. We correlated SBP variability assessed as standard deviation (SBP-SD) and coefficient of variation (SBP-CoV) of the daily measures with overall mortality, cardiovascular mortality and major adverse cardiocerebrovascular events (MACCEs) after a mean follow-up of 49 months by Cox hazard analysis. Results: In our patients (age 68 +/- 11years, 61% hypertensive patients) the ranges of SBP-SD tertiles were: 4.1-9.1, 9.2-11.5 and 11.6-24.5 mmHg. Fifty-five percent of the patients underwent CABG, 33% underwent valve surgery, 12% both CABG and valve surgery. In CABG patients, the highest SBP-SD tertile showed the highest overall mortality, cardiovascular mortality and MACCEs (P &lt; 0.01). Results remained significant after multivariate analysis adjusting for age, sex, mean SBP, BMI, hypertension, hyperlipidaemia, and diabetes. No association between SBP-SD and mortality or MACCEs was found in valve surgery patients. Conclusion: In-hospital day-by-day SBP variability predicts mortality and MACCEs in CABG patients, possibly representing a target during rehabilitation and treatment in secondary cardiovascular prevention

Serum uric acid level predicts adverse outcomes after myocardial revascularization or cardiac valve surgery

Background High levels of serum uric acid have been associated with adverse outcomes in cardiovascular diseases such as myocardial infarction and heart failure. The aim of the current study was to evaluate the prognostic role of serum uric acid levels in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Design We performed an observational prospective cohort study. Methods The study included 1440 patients with available serum uric acid levels, prospectively followed for 50 ± 17 months. Mean age was 67 ± 11 years; 781 patients (54%) underwent myocardial revascularization, 474 (33%) cardiac valve surgery and 185 (13%) valve-plus-coronary artery by-pass graft surgery. The primary endpoints were overall and cardiovascular mortality while secondary end-points were combined major adverse cardiac and cerebrovascular events. Results Serum uric acid level mean values were 286 ± 95 µmol/l and elevated serum uric acid levels (≥360 µmol/l or 6 mg/dl) were found in 275 patients (19%). Overall mortality (hazard ratio = 2.1; 95% confidence interval: 1.5-3.0; p < 0.001), cardiovascular mortality (hazard ratio = 2.0; 95% confidence interval: 1.2-3.2; p = 0.004) and major adverse cardiac and cerebrovascular events rate (hazard ratio = 1.5; 95% confidence interval: 1.0-2.0; p = 0.019) were significantly higher in patients with elevated serum uric acid levels, even after adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate, atrial fibrillation and medical therapy. Moreover, strong positive correlations between serum uric acid level and probability of overall mortality ( p < 0.001), cardiovascular mortality ( p < 0.001) and major adverse cardiac and cerebrovascular events ( p = 0.003) were found. Conclusions Serum uric acid levels predict mortality and adverse cardiovascular outcome in patients undergoing myocardial revascularization and/or cardiac valve surgery even after the adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate and medical therapy