Metformin Acutely Mitigates Oxidative Stress in Human Atrial Tissue: A Pilot Study in Overweight Non-Diabetic Cardiac Patients.

Metformin, the first-line drug in type 2 diabetes mellitus, elicits cardiovascular protection also in obese patients via pleiotropic effects, among which the anti-oxidant is one of the most investigated. The aim of the present study was to assess whether metformin can acutely mitigate oxidative stress in atrial tissue harvested from overweight non-diabetic patients. Right atrial appendage samples were harvested during open-heart surgery and used for the evaluation of reactive oxygen species (ROS) production by means of confocal microscopy (superoxide anion) and spectrophotometry (hydrogen peroxide). Experiments were performed after acute incubation with metformin (10 µM) in the presence vs. absence of angiotensin II (AII, 100 nM), lipopolysaccharide (LPS, 1 µg/mL), and high glucose (Gluc, 400 mg/dL). Stimulation with AII, LPS, and high Gluc increased ROS production. The magnitude of oxidative stress correlated with several echocardiographic parameters. Metformin applied in the lowest therapeutic concentration (10 µM) was able to decrease ROS generation in stimulated but also non-stimulated atrial samples. In conclusion, in a pilot group of overweight non-diabetic cardiac patients, acute incubation with metformin at a clinically relevant dose alleviated oxidative stress both in basal conditions and conditions that mimicked the activation of the renin-angiotensin-aldosterone system, acute inflammation, and uncontrolled hyperglycemia.

Betablockers and Ivabradine Titration According to Exercise Test in LV Only Fusion CRT Pacing.

Background: Betablockers (BB)/ivabradine titration in fusion CRT pacing (CRTP) is understudied. Aim: To assess drug optimization using systematic exercise tests (ET) in fusion CRTP with preserved atrioventricular conduction (AVc). Methods: Changes in drug management were assessed during systematic follow-ups in CRTP patients without right ventricle lead. Shorter AVc (PR interval) allowed BB up-titration, while longer AVc needed BB down-titration, favoring ivabradine. Constant fusion pacing was the goal to improve outcomes. Results: 64 patients, 62.5 ± 9.5 y.o divided into three groups: shorter PR (<160 ms), normal (160−200 ms), longer (200−240 ms); follow-up 59 ± 26 months. Drugs were titrated in case of: capture loss due to AVc shortening (14%), AVc lengthening (5%), chronotropic incompetence (11%), maximum tracking rate issues (9%), brady/tachyarrhythmias (8%). Interventions: BB up-titration (78% shorter PR, 19% normal PR, 5% longer PR), BB down-titration (22% shorter PR, 14% normal PR), BB exclusion (16% longer PR), adding/up-titration ivabradine (22% shorter PR, 19% normal PR, 5% longer PR), ivabradine down-titration (22% shorter PR, 3% normal PR), ivabradine exclusion (11% normal PR, 5% longer PR). Drug strategy was changed in 165 follow-ups from 371 recorded (42% patients). Conclusions: BBs/ivabradine titration and routine ET during follow-ups in patients with fusion CRTP should be a standard approach to maximize resynchronization response. Fusion CRTP showed a positive outcome with important LV reverse remodeling and significant LVEF improvement in carefully selected patients.

Morphological Study of Fossa Ovalis in Formalin-Fixed Human Hearts and Its Clinical Importance.

Background and Objectives: Our study aimed to investigate the gross anatomy aspects of the fossa ovalis (FO) and the presence of some anatomical variation resulting from the incomplete fusion of septum primum and septum secundum, such as an atrial septal pouch (SP) and left atrial septal ridge. Materials and Methods: Thirty-one adult human hearts removed from formalin-fixed specimens were examined to provide information about the morphology of the FO. The organs were free of any gross anatomically visible pathological conditions. Results: The most common variants were the FO located in the inferior part of the interatrial septum (64.51%), circular (61.3%), with a net-like structure (51.62%), prominent limbus (93.55%), and patent foramen ovale (PFO) (25.8%). The right SP was observed in 9.67% of specimens, the left SP was observed in 29.03% of cases, and in 51.61% of cases, a double SP was observed. One sample presented a right SP and a double left SP, and one case showed a triple left SP, which was not reported previously to our knowledge. Conclusions: Knowledge of the interatrial septal anatomy becomes important for interventional cardiologists and should be documented before transeptal puncture.

A Novel and Simple Exercise Test Parameter to Assess Responsiveness to Cardiac Resynchronization Therapy.

This study assessed the value of heart rate recovery index (HRRI), a new parameter of an exercise test, as the predictor of response to cardiac resynchronization therapy (CRT). Methods: Consecutive patients receiving a CRT device were followed up after implantation and every 6 months. An effort test (ET) was quantified by minimum heart rate/maximum heart rate, as well as acceleration and deceleration times. HRRI was calculated as the ratio between acceleration and deceleration time (AT/DT) and compared to outcome. We used logistic regression to assess the predictive value of HRRI for responders and non-responders to CRT. The area under the curve (AUC) was computed to distinguish between positive and negative outcomes. Results: A total of 109 patients (74 men, mean age 63.3 ± 9.8 years) were analyzed; permanent long-term fusion CRT pacing was possible in 65 patients. Patients were assigned to two groups: responders and non-responders (98/11 patients). During a mean follow-up of 36 months, 545 ETs were performed. HRRI was significantly higher in responders versus non-responders (3.16 ± 2 vs. 1.4 ± 0.5, p < 0.001). The optimal cutoff value for HRRI as a predictor of CRT response was 1.51 (area under the receiver operating characteristic (ROC) curve = 0.844). Responders had significant left-ventricular (LV) reverse remodeling (LV end-diastolic volume = 240 ± 90 mL vs. 217 ± 89 mL, p < 0.001) and higher LV ejection fraction (26 ± 5.8% vs. 35 ± 8.7%, p < 0.001). Conclusions: HRRI computation during routine ET is useful for the evaluation of responsiveness to CRT.

An Insight into the Structural Diversity and Clinical Applicability of Polyurethanes in Biomedicine.

Due to their mechanical properties, ranging from flexible to hard materials, polyurethanes (PUs) have been widely used in many industrial and biomedical applications. PUs' characteristics, along with their biocompatibility, make them successful biomaterials for short and medium-duration applications. The morphology of PUs includes two structural phases: hard and soft segments. Their high mechanical resistance featuresare determined by the hard segment, while the elastomeric behaviour is established by the soft segment. The most important biomedical applications of PUs include antibacterial surfaces and catheters, blood oxygenators, dialysis devices, stents, cardiac valves, vascular prostheses, bioadhesives/surgical dressings/pressure-sensitive adhesives, drug delivery systems, tissue engineering scaffolds and electrospinning, nerve generation, pacemaker lead insulation and coatings for breast implants. The diversity of polyurethane properties, due to the ease of bulk and surface modification, plays a vital role in their applications.

Therapeutic approach comparison in bicuspid aortic valve aortopathy and clinical practice implications.

Bicuspid aortic valve (BAV) is the most common heart valve malformation, and it may be associated with the development of long-term complications, such as aortic stenosis (AS) secondary to valvular calcification and aortic insufficiency (AI), with or without ascending aortic aneurysm (AAA). This study was performed at the Institute of Cardiovascular Diseases, Timisoara, Romania, from 2015 through 2018 and included a total of 105 patients with BAV. Out of the 105 BAV patients, 14 displayed AAA, alongside either AS or AI, and were selected undergo aortic valve replacement (AVR) alongside surgical replacement or aortoplasty of the ascending aorta, and the elastic fiber loss in the ascending aortic wall was evaluated for each patient. Two surgical interventions used alongside AVR in BAV patients with AAA and AS or AI were compared in this study: reduction ascending aortoplasty (RAA) and ascending aorta replacement (AAR). Postoperative follow-ups have shown RAA is useful short-term but that, in contrast to AAR, it leads to aortic redilatation over time. These results can contribute to a major future meta-analysis with the goal of improving the current clinical practice guidelines for BAV aortopathy.

Chameleonic appearance of caseous calcification of the mitral valve - still a problem for its appropriate management.

According to the research literature, the caseous calcification of the mitral annulus (CCMA) is a rare variant of the mitral annulus calcification (MAC) entity, described mostly in elderly women. The aim of this study was to present the case of a 53-year-old female patient with caseous calcification of the mitral valve annulus and posterior cusp, which was diagnosed as papillary fibroelastoma. An echo-dense and quasi-homogeneous tumoral mass, measuring 1.6∕1.4 cm, at the level of the posterior mitral ring was detected by echocardiographic examination, as well as by cardiac magnetic resonance imaging (MRI). Histopathological analysis revealed fibrous connective tissue with myxoid areas, hyaline degeneration with unstructured necrosis and dystrophic calcifications, which was consisting with the operative findings of a "toothpaste tumor", or caseous calcification of the mitral valve. Differential diagnosis with other cardiac tumors, abscesses, thrombi or fibroelastomas is emphasized.

The Importance of DS-14 and HADS Questionnaires in Quantifying Psychological Stress in Type 2 Diabetes Mellitus.

Background and Objectives: The comorbid association between type 2 diabetes mellitus (T2DM) and a psychological profile characterized by depression and/or anxiety has been reported to increase the risk of coronary heart disease (CAD), the most striking macrovascular complication of diabetes. The purpose of the present study was to quantify anxiety, depression and the presence of type D personality, and to correlate the scores obtained with cardiovascular risk factors and disease severity in diabetic patients. Materials and methods: The retrospective study included 169 clinically stable diabetic patients divided into two groups: group 1 without macrovascular complications (n = 107) and group 2 with CAD, stroke and/or peripheral vascular disease (n = 62). A biochemical analysis and an assessment of psychic stress by applying the Hospital Anxiety and Depression Scale (HADS)and the Type D scale (DS-14) to determine anxiety, depression and D personality scores were done in all patients. Statistical analysis was made using SPSSv17 and Microsoft Excel, non-parametric Kruskal-Wallis and Mann-Whitney tests. Results: Following application of the HAD questionnaire for the entire group (n = 169), anxiety was present in 105 patients (62.2%), and depression in 96 patients (56.8%). Group 2 showed significantly higher anxiety scores compared to group 1 (p = 0.014), while depression scores were not significantly different. Per entire group, analysis of DS-14 scores revealed social inhibition (SI) present in 56 patients (33%) and negative affectivity (NA) in 105 patients (62%). TheDS-14 SI score was significantly higher in group 2 compared to group 1 (p = 0.036). Type D personality, resulting from scores above 10 in both DS-14 parameter categories, was present in 51 patients of the study group (30%). There was a direct and significant correlation (r = 0.133, p = 0.025) between the Hospital Anxiety and Depression Scale-Anxiety (HAD-A) score and the LDL-c values. Conclusions: The results of this study demonstrated that more than a half of patients with diabetes had anxiety and/or depression and one third had Type D personality, sustaining that monitoring of emotional state and depression should be included in the therapeutic plan of these patients. New treatment strategies are needed to improve the well-being of diabetic patients with psychological comorbidities.

Back to sinus rhythm from atrial flutter or fibrillation: dabigatran is safe without transoesophageal control.

BACKGROUND AND AIM: To assess the safety of dabigatran in converting persistent atrial fibrillation (PAF) and atrial flutter (AFL) to sinus rhythm (SR) without transoesophageal echocardiography (TEE) evaluation. METHODS: Consecutive patients with PAF or AFL were included between 2012 and 2015. Dabigatran was used for three weeks before and six months after cardioversion. Left atrium area (LAA) and left atrium volume (LAV) were assessed in all patients. Follow-up visits for major cardiac events occurred at 1, 3, 6, and 12 months. RESULTS: The study included 82 patients (56 male, mean age 63.1 ± 10.4 years), of which 45 had PAF and 37 AFL. In patients with PAF, mean LAA was 30.3 ± 5.3 cm2 and LAV 114.4 ± 31.5 mL; in those with AFL mean LAA was 26.5 ± 4.2 cm2 and LAV 97 ± 24.9 mL at baseline. Forty-nine patients underwent uncomplicated electric cardioversion (38 with PAF and 11 with AFL), 11 patients were pharmacologically converted to SR (7 with PAF and 4 with AFL), and 22 patients with AFL underwent successful radiofrequency ablation. The mean CHA2DS2-VASc score was 2.96 ± 1.39 (score > 3, 58.6%). No major cardiac events occurred during the follow-up period of 19.4 ± 9.5 months. CONCLUSIONS: Safe cardioversion using dabigatran was achieved in this small group of patients without the need for TEE.

Subclinical left atrium remodelling in patients with frequent premature ventricular contractions.

BACKGROUND: Premature ventricular contractions (PVCs) may cause subtle changes in left atrium (LA) structure and function which may not be readily detected by conventional parameters. AIM: To explore the relationship between PVCs and LA shape and size remodelling in patients without known structural heart disease. METHODS: PVC frequency per 24 h was divided into tertiles. Echocardiographic measurements included left ventricular ejection fraction (LVEF) and volume, LA volume (LAV), mid-LA transverse diameter (LAt), and basal LA maximal transverse diameter (LAb). Trapezoidal LA shape was defined by LAt less than LAb. The association between PVCs and LA shape was explored by multivariable adjusted logistic regression. RESULTS: The 121 patients had a mean age of 43.1 years (63% male) and mean LVEF of 56%. Mean LAV was 57.7 mL in the lowest PVC tertile, 70.9 mL in the middle, and 87.1 mL in the highest PVC tertile (p < 0.001). Trapezoidal LA shape was documented in 32 patients. Five per cent of patients in the lowest and 65% in the highest PVC tertile had trapezoidal LA shape (p < 0.001). PVC frequency correlated with LAV (r = 0.87, p < 0.001) and LAb (r = 0.56, p < 0.001). Each 10% increase in PVCs was significantly associated with trapezoidal LA shape (OR = 1.32, 95% CI 1.17-1.48), after adjustment for age, sex, mean blood pressure, LVEF, and LV end-diastolic diameter. CONCLUSIONS: Frequent PVCs are associated with larger LAV and trapezoidal LA shape in otherwise healthy patients, suggesting LA remodelling in response to increased LV filling pressure.