Long-term follow-up and safety assessment of angiogenic gene therapy trial VIF-CAD: Transcatheter intramyocardial administration of a bicistronic plasmid expressing VEGF-A165/bFGF cDNA for the treatment of refractory coronary artery disease.

There have been a number of angiogenic gene therapy trials, yielding mixed results as to efficacy, but demonstrating uniform short-term treatment safety. Data regarding long-term safety of angiogenic gene therapy are limited. Double-blind VIF-CAD trial (NCT00620217) assessed myocardial perfusion and clinical data in 52 refractory coronary artery disease (CAD) patients randomized into treatment (VIF; n = 33) and Placebo (n = 19) arms. VIF group received electromechanical system NOGA-guided intramyocardial injections of VEGF-A165/bFGF plasmid (VIF) into ischemic regions, while the Placebo group-placebo plasmid injections. Full 1-year follow-up data have been published. This study presents the results of over 10-year (median 133 months, range 95-149) safety follow-up of VIF-CAD patients. Overall, 12 (36.4%) patients died in VIF and 8 (42.1%) in Placebo group (P = .68). Cardiovascular mortality was 12/33 (36.4%) in the VIF group and 6/19 (31.6%) in Placebo group (P = .73). Two Placebo patients died due to malignancies, but no VIF patients (P = .17). The Kaplan-Meier curves of combined endpoint: cardiovascular mortality, myocardial infarction and stroke were similar for both patient groups (P = .71). Odds ratio of Placebo group increasing (reaching a worse) their CCS class versus VIF was non-significant (OR 1.28, 95% CI = 0.66-2.45; P = .47). However, CCS class improved in time irrespectively of treatment-OR of reaching a less favorable CCS class per each year of follow-up was 0.74 (95% CI 0.685-0.792; P < .0001, pooled data). There were no differences in readmission rates. Intramyocardial VEGF-A165/bFGF plasmid administration appears safe, with no evidence of an increase in the incidence of death, malignancy, myocardial infarction or stroke during 10-year follow-up in this limited patient population.

Native T1-mapping for non-contrast assessment of myocardial fibrosis in patients with hypertrophic cardiomyopathy--comparison with late enhancement quantification.

BACKGROUND: Myocardial fibrosis was shown to influence prognosis in hypertrophic cardiomyopathy (HCM). It is typically assessed by late gadolinium enhancement (LGE) on cardiac magnetic resonance. Native T1-mapping has been proposed, as a contrast-free method of fibrosis assessment. The aim of the study was to define a cut-off value for native T1 relaxation time that best reflects LGE quantification of myocardial fibrosis. METHODS: In 25 patients with HCM and 20 controls we performed T1-mapping pre-contrast using ShMOLLI technique. This was followed by LGE assessment in the studied group 10 minutes after gadolinium contrast injection. Relative myocardial fibrosis size was calculated for varying T1 time thresholds (940-1100 ms) and compared with 6 standard deviations (6SD) method for LGE. RESULTS: Median fibrosis size calculated with T1-mapping was insignificantly different from LGE only for native T1 time threshold of 1060 ms (p = 0.62). Using this threshold, Bland-Altman plots demonstrated very good agreement between fibrosis sizes from the two methods (slightly better only for 1080 ms threshold). For threshold of 1060 ms we also observed good correlation (rho = 0.73) with LGE 6SD method (insignificantly better for lower thresholds, best for threshold of 980 ms-rho = 0.88). In control group with no diagnosis of HCM, fibrosis size <1% was reached for thresholds of 1040 ms and higher. CONCLUSION: Native T1-mapping can be used for non-contrast assessment of myocardial fibrosis in HCM. The 1060 ms threshold of the native T1 relaxation time is characterized by the best balance between agreement and correlation with fibrosis assessed by LGE 6SD method.

Validation of Mini Nutritional Assessment Scale in peritoneal dialysis patients.

INTRODUCTION: Malnutrition is a negative predictive factor for survival in end stage renal disease (ESRD) patients. Coincidence of malnutrition, inflammation and atherosclerosis (MIA syndrome) in the dialysis population is an exceptionally poor outcome event. Due to flexibility, ease of performance and reproducibility, clinical scales are of particular value in assessment of nutritional status in ESRD patients. The aim of the present study was to evaluate the clinical value of Mini Nutritional Assessment (MNA) in peritoneal dialysis (PD) patients. MATERIAL AND METHODS: Nutritional status was assessed in 41 peritoneal dialysis patients by means of the MNA scale and malnutrition inflammation score (MIS). Some other clinical and laboratory parameters associated with nutritional status were analyzed. Patients were followed up for 30 months. RESULTS: In the analyzed group of patients a good nutritional state was diagnosed in 22 patients (54%), risk of malnutrition in 17 (41%) and malnutrition in 2 patients (5%) based on the MNA scale. A strong correlation between MNA based nutritional status and MIS was found (r = -0.85, p < 0.01, ANOVA, p < 0.01). Differences in time on dialysis, body mass index, concentration of albumin, cholesterol and triglycerides were noted between at risk/malnourished and well-nourished (according to MNA) patients. Statistically significant factors determining survival of patients by Cox proportional hazard analysis were age (HR 1.07), being at risk/malnourished according to MNA (HR 5.7), MIS (HR 1.2), and albumin (HR 0.13). CONCLUSIONS: The MNA scale is a valuable, clinically suitable tool for assessment of nutritional status in peritoneal dialysis patients. Risk of malnutrition and malnutrition diagnosed by MNA identifies patients at high mortality risk.