Safety and Efficacy of Sacubitril/Valsartan in Patients With a Failing Systemic Right Ventricle: A Prospective Single-Center Study.

BACKGROUND: Sacubitril/valsartan was demonstrated to reduce hospitalization rate and mortality in patients with heart failure with reduced ejection fraction. Data on the effects of sacubitril/valsartan in patients with a systemic right ventricle are still lacking. METHODS: Patients with transposition of the great arteries following Senning/Mustard procedure or congenitally corrected transposition of the great arteries with impaired systemic right ventricle systolic function were prospectively included. Primary end points included sacubitril/valsartan safety and efficacy. Primary efficacy end points were NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic function improvement. Secondary end points included New York Heart Association class, 6-minute walking distance, and quality of life change. RESULTS: Fifty patients (38±12 years, 60% male, 35% congenitally corrected transposition of the great arteries) were included and followed for 1 year. No major adverse events occurred. Two (4%) patients ceased treatment due to hypotension and 1 (2%) developed a nephrotic syndrome. The target dose was reached in 20 (42%) patients. NT-proBNP values decreased significantly immediately after treatment initiation, while returned to baseline at 1 year. Echocardiography showed progressive fractional area change increase (29.2±5.8 versus 34.9±5.1%; P<0.001), and right ventricle global longitudinal strain (-13.9 [-15.1, -11.8] versus -15.3 [-17.2, -13.4]%; P<0.001) and free-wall global longitudinal strain (-14.3 [-17.3, -12.3] versus -17.2 [-19.3, -15.8]%; P<0.001) raise, whereas tricuspid regurgitation severity improved only in transposition of the great arteries patients (P=0.006). Moreover, 3-dimensional echocardiography demonstrated right ventricle volumes reduction (end-diastolic volume: 181±63 versus 156±50 mL; P=0.002; end-systolic volume: 117±48 versus 89±33 mL; P<0.001), and significantly increased systemic right ventricle ejection fraction (35.6±8.1 versus 41.5±7.5%; P<0.001). Clinical improvement was suggested by New York Heart Association class change (P<0.001), increased 6-minute walking distance (425 [333, 480] versus 500 [443, 560] m; P<0.001) as well as improved quality of life at 1-year follow-up. Beneficial effects were observed irrespective of the underlying anatomy and were more pronounced in those on target dose. CONCLUSIONS: Our data showed that sacubitril/valsartan is well tolerated and is associated with systemic right ventricle remodeling and improved systolic function as well as improved clinical status, supporting its use in this complex population.

Left atrial appendage thrombus on full-dose dabigatran treatment: a case report.

BACKGROUND: Dabigatran is a direct competitive thrombin inhibitor approved for stroke prevention in non-valvular atrial fibrillation. At full-dose, dabigatran showed similar rates of bleedings and higher efficacy compared to warfarin. CASE SUMMARY: We report a case of acute ischaemic stroke in a patient treated with dabigatran 150 mg b.i.d. for atrial fibrillation. After an off-label treatment with idarucizumab, a humanized monoclonal antibody approved for dabigatran reversal, we performed a successful intravenous thrombolysis (IVT). Transoesophageal echocardiography showed a left atrial appendage (LAA) thrombus, despite full-dose dabigatran and an adequate therapy adherence. DISCUSSION: There are few cases of LAA thrombus during dabigatran treatment reported in literature till date. We analyse the possible pathogenetic mechanisms involved in dabigatran failure, including drug interactions and unexpected genetic variations interfering with dabigatran serum levels suggesting periodical assessment of direct Oral Anticoagulant levels. Furthermore, we confirm initial reports of safety and efficacy of intravenous thrombolysis after idarucizumab, in case of dabigatran failure.

A nutraceutical combination reduces left ventricular mass in subjects with metabolic syndrome and left ventricular hypertrophy: A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH). METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM > 48 g/m2.7 in men and > 44 g/m2.7 in women), were randomized 1:1 to receive AP or placebo for 24 weeks. Reduction of LVM, regression of LVH, and changes in lipids were analysed. RESULTS: One-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p < 0.0001), and compared to placebo (-4.1%, p < 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile. CONCLUSIONS: 24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176.

Arterial wave reflections and ventricular-vascular interaction in patients with left ventricular systolic dysfunction.

Central aortic pressure waveform (AoPW) is the summation of a forward-traveling wave generated by the left ventricle and a backward-traveling wave caused by the reflection of the forward wave. The aim of this study was to evaluate the effect of ventricular-vascular coupling on the morphology of AoPW in chronic heart failure patients with different degrees of left ventricular systolic dysfunction (LVSD) using pulse wave analysis (PWA). PWA of AoPW and left ventricular (LV) function were evaluated by applanation tonometry in 26 control subjects, in 12 patients with left ventricular ejection fraction (LVEF) ≤ 30%, and in 14 patients with LVEF > 30%. Augmentation pressure, augmentation index, wasted energy, and ejection duration were lower in patients with LVEF ≤ 30% than in those with LVEF > 30% and in control subjects. Furthermore, augmentation index showed an inverse correlation with Doppler mitral E-wave amplitude (r = -0.40; P = 0.04) and E/A ratio (r = -0.42; P = 0.03) and a direct correlation with deceleration time of mitral E-waves (r = 0.39; P = 0.04). In patients with severe LVSD (LVEF ≤ 30%), aortic wave reflections negatively interfere with LV function and induce a shortening of ejection duration. In contrast, AoPW is similar in patients with moderate LVSD (LVEF > 30%) and in control subjects.

Effects of cigarette smoking on the human urinary proteome.

In this pilot study we used a proteomic approach to compare the urinary protein patterns of healthy smokers and non-smokers. Proteins were resolved by two-dimensional gel electrophoresis and identified by mass spectrometry. The relative abundance of three inflammatory proteins (S100A8, inter-alpha-trypsin inhibitor heavy chain 4, CD59) and that of two isoforms of pancreatic alpha amylase was significantly higher in smokers. Zinc-alpha-2-glycoprotein was the only protein down-regulated in smokers. Its abundance was significantly correlated with urinary glucocorticoids. Most of the proteins identified may be non-specific biomarkers of tobacco effects, since they are involved in inflammatory responses associated with several diseases. Of greater interest are the changes in abundance of pancreatic alpha amylase and zinc-alpha-2-glycoprotein, which after proper validation, might be candidate biomarkers of diseases resulting from exposure to tobacco smoke. The data also show for the first time that smoking can affect the expression profile of urinary proteins.