Therapeutic Applications of Calcium Metabolism Modulation in Heart Disease.

Cardiovascular disease is the leading cause of death worldwide and there is extensive research on the pathophysiology of all its clinical entities. Despite the big array of possible therapeutic modalities for cardiovascular disease, there is still a big necessity to develop novel treatments that will augment our strategies for tackling the burden of cardiovascular disease and decrease morbidity and mortality. A major player in both the physiology and pathophysiology of the cardiovascular system is calcium. Extracellular calcium is required in order to initiate cardiac muscle contraction and promote the calcium-induced calcium release mechanism from the sarcoplasmic reticulum. A lot of molecules and structures that in a direct or indirect way interact with calcium are being studied and there is a constant flow of new information that is emerging. In this review we focus on some of these calcium metabolism modulators representatives such as SERCA2a, RyR2, S100A1, phosholamban and calcineurin. We emphasize on their mechanism of action, their role in cardiovascular disease and potential therapeutic implications. We also focus on the effect the bisphosphonates might have in regression of the calcium deposition in the human arteries as well as the usage of novel biomarkers such as mircoRNAs in calcium metabolism modulation in heart disease.

One-year outcomes after direct transcatheter aortic valve implantation with a self-expanding bioprosthesis. A two-center international experience.

BACKGROUND: Balloon aortic valvuloplasty (BAV) is considered to be an essential part of the transcatheter aortic valve implantation (TAVI) procedure and is being performed routinely. At present there is insufficient long-term data as to the benefits of routine BAV prior to TAVI. AIM: The aim of this study was to evaluate the safety of direct TAVI and the mortality rate at 1-year in patients undergoing TAVI with or without BAV with a self-expanding bioprosthesis. METHODS: Between January 2008 and September 2013 consecutive patients undergoing TAVI with the Medtronic CoreValve in two experienced centers in Athens, Greece and in Siegburg, Germany were studied. All data were prospectively collected and retrospectively analyzed. Primary endpoint was mortality at 1 year. Procedural data and clinical data (bleeding, vascular complications and echocardiographic parameters) were analyzed. RESULTS: A total of 210 patients undergoing TAVI were evaluated (non-direct=120 patients, direct=90 patients). All-cause mortality at 30 days and at 1 year was similar in both groups (4% in non-direct versus 2% in direct, p=0.6 and 15% in non-direct versus 11% in direct, p=0.5, respectively). Device success rate was similar in both groups (77% in non-direct versus 83% in direct, p=0.2). Major vascular complications were comparable for both groups (5% in non-direct versus 3% in direct, p=0.5). The direct group had less moderate/severe paravalvular leakage than the non-direct group after the device implantation (7% versus 33%, p<0.01). CONCLUSIONS: Performing direct TAVI with the self-expanding bioprosthesis is safe and feasible showing similar mortality rates compared to patients undergoing non-direct TAVI at 30 days and at 1-year.

Percutaneous mitral valvuloplasty refined: use of a novel modified antegrade approach.

Mitral stenosis usually occurs many years after an episode of rheumatic fever and it has an indolent course until its later stages, when it acutely worsens. The rates of mitral stenosis keep declining; nonetheless, the need for advanced and sophisticated treatment modalities still remains. Our group has been applying a novel modified antegrade approach for treating mitral valve stenosis and, although we have limited experience, the results thus far are favorable. We present the preliminary data of three patients who suffered from symptomatic mitral valve stenosis and underwent successful percutaneous mitral valvuloplasty with this novel modified antegrade approach. This method increases the safety and the efficacy of the procedure and has the same clinical results as other available percutaneous techniques.

Upgrading pacemaker to cardiac resynchronization therapy: an option for patients with chronic right ventricular pacing and heart failure.

INTRODUCTION: Long-term pacing from the right ventricle (RV) has been shown to induce a deleterious effect on left ventricular function. Cardiac resynchronization therapy (CRT) is an established treatment for heart failure (HF) patients. The purpose of this study was to assess the benefit from upgrading to CRT in chronically RV-paced patients with a low left ventricular ejection fraction (LVEF<35%). METHODS: Thirty-seven HF patients (age 71.4 ± 7.7, 26 male), who fulfilled CRT indications, were included. Study subjects had undergone VVI or DDD pacemaker implantation 6.1 ± 5.7 years earlier and were referred to our centre because of worsened clinical condition or a depleted battery. Patients were assessed at baseline and six months after CRT. Evaluation included NYHA classification, functional capacity assessed by six-minute walk test (6 MWT), hospitalization rate and echocardiographic assessment. RESULTS: Biventricular pacing was possible in 34 of the 37 cases (91.7%) who had their device upgraded to CRT-P (n=8) or to CRT-D (n=26). After the implementation of CRT the patients showed a noteworthy clinical improvement. Average NYHA class changed from 3.3 ± 0.6 to 2.5 ± 0.9 (p<0.001), 6 MWT performance increased from 246 ± 105 m to 321 ± 101 m (p<0.001), while six-month hospitalization rate dropped from 1.4 ± 1 to 0.7 ± 0.8 admissions (p<0.001). LVEF increased from 26.3 ± 5.4% to 31.4 ± 6.7% (p<0.001) and left ventricular end-systolic volume changed from 134.3 ± 46 mL to 111.9 ± 41.1 mL (p<0.001). A reduction in QRS duration by 28 ms (p<0.001) was also noted. CONCLUSIONS: RV-paced patients should be closely monitored, and upgrade to CRT should be considered promptly if they develop moderate or severe HF.