Ranolazine reduces symptoms of palpitations and documented arrhythmias in patients with ischemic heart disease — The RYPPLE randomized cross-over trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520)

Glyco-metabolic Effects of Ranolazine: A truly Multifaceted Drug?

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Additive effects of nutraceuticals to non-pharmacologic intervention to improve lipid profile in the real world clinical practice in European countries — The PIN (Portugal Italy Nutraceutical) Study

PEARL trial. Patientswere randomly assigned to atorvastatin (20 mg day, N= 50) or rosuvastatin (10 mg day, N= 50) for 30 days. After another 1-week wash-out period to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days. Platelet reactivity (expressed as P2Y(12) reaction units (PRU) by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) was measured before and at the end of each 30-day treatment period. High platelet reactivity after clopidogrel was defined as a PRU value N 208. Results: After the 30-day treatment with atorvastatin, platelet reactivity did not significantly change as compared with baseline, pre-treatment evaluation (119 ± 66 vs 136 ± 59 PRU, NS), with 2 patients only showing a PRU N 208. Similarly, after 30-day treatment with rosuvastatin, platelet reactivity was unchanged as compared with baseline (135 ± 46 vs 128 ± 62 PRU, NS), with PRU N 208 occurring in 3 patients. Conclusion: Atorvastatin does not negatively affect DAPT as compared with rosuvastatin when is given to stable CAD patients with baseline normal platelet reactivity while on DAPT. (ClinicalTrials.gov Identifier: NCT01567774)

Testosterone Therapy in Women With Chronic Heart Failure A Pilot Double-Blind, Randomized, Placebo-Controlled Study

ObjectivesThe primary objective of this study was to assess the effect of a 6-month testosterone supplementation therapy on functional capacity and insulin resistance in female patients with chronic heart failure (CHF).BackgroundPatients with CHF show decreased exercise capacity and insulin sensitivity. Testosterone supplementation improves these variables in men with CHF. No study has evaluated the effects of testosterone supplementation on female patients with CHF.MethodsThirty-six elderly female patients with stable CHF, (ejection fraction 32.9 ± 6) were randomly assigned (2:1 ratio) to receive testosterone transdermal patch (T group, n = 24) or placebo (P group, n = 12), both on top of optimal medical therapy. At baseline and after 6 months, patients underwent 6-min walking test (6MWT), cardiopulmonary exercise test, echocardiogram, quadriceps maximal isometric voluntary contraction, dynamic quadriceps isokinetic strength (peak torque), and insulin resistance assessment by homeostasis model.ResultsDistance walked at 6MWT as well as peak oxygen consumption significantly improved in the T group, whereas they were unchanged in the P group (p < 0.05 for all comparisons). The homeostasis model was significantly reduced in the T group in comparison with the P group (−16.5% vs. +5%, respectively; p < 0.05). Maximal voluntary contraction and peak torque increased significantly in the T group but did not change in the P group. Increase in distance walked at 6MWT was related to the increase in free testosterone levels (r = 0.593, p = 0.01). No significant changes in echocardiographic parameters were observed in either group. No side effects requiring discontinuation of T were detected.ConclusionsTestosterone supplementation improves functional capacity, insulin resistance, and muscle strength in women with advanced CHF. Testosterone seems to be an effective and safe therapy for elderly women with CHF

Tai Chi Enhances the Effects of Endurance Training in the Rehabilitation of Elderly Patients with Chronic Heart Failure

Purpose. To assess if Tai Chi added to endurance training (ET) is more effective than ET alone in improving exercise tolerance and quality of life (QOL) of elderly patients with chronic heart failure (CHF). Design. Sixty CHF patients, age 73.8 ± 6 years, M/F 51/9, were enlisted. Thirty pts were randomized to combined training (CT) performing Tai Chi +ET and 30 patients to ET (ET only). Methods. At baseline and after 12 weeks all patients underwent 6-minute walking test (6MWT), assessment of amino terminal probrain natriuretic peptide (NT-pro BNP), quadriceps maximal voluntary contraction (MVC) and peak torque (PT), QOL questionnaire (MacNewQLMI), blood pressure (BP), and heart rate (HR). All patients performed 4 sessions of exercise/week. Results. Distance at 6mwt improved in both groups with significant between-groups differences (P = .031). Systolic BP and NT-proBNP decreased significant in the CT group compared to ET (P = .025) and P = .015), resp.). CT group had a greater significant improvement in physical perception (P = .026) and a significant increase of PT compared to ET group. Conclusions. The association of Tai Chi and ET improves exercise tolerance and QOL of patients with CHF more efficiently than ET

Intensive cardiac rehabilitation improves glucometabolic state of non-diabetic patients with recent coronary artery bypass grafting

Background: The aim of this study is to examine the effect of an intensive CR program early after coronary artery bypass grafting on glucometabolic state of non-diabetic patients with CAD. Methods: 60 patients were included in the study. All patients underwent Oral Glucose Tolerance Test (OGTT), Homeostasis Model Assessment (HOMA) Index and Six Minutes Walking Test at baseline and at the end of CR. The patients were then included in a 3-month follow-up program. Results: At baseline 61% of the patients had normal fasting glucose, while after OGTT 28.3% had normal glucose tolerance, 41.6% had impaired glucose tolerance (IGT), and 30.1% had type 2 diabetes mellitus (T2DM). At the end of the CR program the number of patients with T2DM was significantly lower (−22%, p < 0.05) while the number of normal glucose tolerance patients had significantly increased (+26%; p < 0.05). T2DM and IGT patients showed worse performances at Six Minutes Walking Test than normal glucose tolerance patients at baseline but had a similar improvement after 4 weeks of training. After 3 months follow-up fasting blood glucose, insulin levels and HOMA index were increased compared to 4 week values, but were lower than baseline. Conclusion: OGTT is important to evaluate glucometabolic state of CAD patients. Intensive CR improves glucometabolic state and insulin resistance in CAD patients with impaired glucose metabolism

Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens