Transcatheter Tricuspid Valve Interventions: A Triumph for Transcatheter Procedures?

Tricuspid regurgitation (TR) is a common valvular pathology, estimated to affect 1.6 million people in the United States alone. Even though guidelines recommend either medical therapy or surgical treatment for TR, the misconception of TR as a benign disease along with the high mortality rates of surgical intervention led to undertreating this disease and commonly describing it as a "forgotten" valve. Recently, the development of transcatheter interventions for TR show promising potential for use in the clinical setting. There are currently few approved and numerous tested percutaneously delivered devices, which can be categorized, based on their mechanism of action, to either valve repair or valve replacement procedures. Both procedures were tested in clinical trials and show an echocardiographic reduction in TR sustained for at least 1 year after the procedure, as well as symptom relief and functional improvement of the patients. Device selection should be personalized, taking into consideration the anatomy of each valve and the available options at each heart center. Moreover, appropriate patient selection and timing of the procedure are also crucial for the success of the procedure. In this review, we analyze the clinical trials available for all devices currently approved or tested, aiming to provide a comprehensive summary of the most recent evidence in the field of transcatheter TR interventions.

Incidence and Prevalence of Cardiac Arrhythmias in Pericardial Syndromes.

Arrhythmias in pericardial syndromes have been poorly investigated and available data are mainly obtained from relevant studies however having different endpoints from arrhythmias. Thus, the incidence and prevalence of any type of arrhythmias may be actually higher than generally considered. Atrial arrhythmias, mainly atrial fibrillation and flutter have been reported as the most common rhythm disturbances in the setting of acute pericarditis. Concerning pathophysiology of atrial arrhythmias, in contrast to earlier hypothesis that they occur exclusively in the presence of an underlying structural heart disease, recent data support an arrhythmogenic potential of acute pericardial inflammation regardless of the presence of heart disease. In cases of myopericarditis, namely primarily pericarditis with evidence of myocardial involvement (i.e., troponin elevation without however overt left ventricular dysfunction and/or segmental wall motion abnormalities), ventricular arrhythmias appear to prevail. With reference to the rest of pericardial syndromes data on arrhythmias development are even more sparce. In particular, in constrictive pericarditis atrial tachyarrhythmias are the most commonly detected and seem to be related to disease severity and possibly to the underlying etiology. In this review we have summarized the available information on the incidence and prevalence of arrhythmias in pericardial syndromes. We wish to emphasize that the clinical significance of arrhythmias in this setting in terms of prognosis and optimal medical treatment (including need and safety of anticoagulation in atrial fibrillation/flutter complicating acute pericarditis), should be further investigated.

Beneficial Effects of Sildenafil on Tissue Perfusion and Inflammation in a Murine Model of Limb Ischemia and Atherosclerosis.

BACKGROUND: Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has endothelium protective and angiogenic effects. OBJECTIVES: To test if sildenafil improves tissue perfusion and neovascularization and downregulates proinflammatory molecules following limb ischemia. METHODS: 30 ApoE-/- male mice, bred with cholesterol rich diet for 4 weeks, were anesthetized and underwent unilateral hind-limb ischemia with ligation of the left femoral artery. Mice were randomized in 2 groups: sildenafil (1 mg/Kg for 7 days intraperitoneally, i.p.) or normal saline (0.4 ml for 7 days, i.p.). Bilateral hind-limb perfusion was estimated by laser Doppler imaging after surgery on days 0, 7 and 28. RESULTS: Sildenafil significantly reduced at day 28 compared with day 0 levels of soluble intracellular adhesion molecule-1(sICAM-1) [2.24(1.81-2.41) vs. 1.29(0.87-1.45) ng/ml, p=0,01], soluble E-selectin (sE-Selectin) [5.52 (3.67-6.14) vs 1.71 (1.42-2.86) ng/ml, p=0.02] and tissue plasminogen activator inhibitor- 1 (tPAI-1) [0.13(0.07-0.21) vs 0.08 (0.04-0.10) ng/ml, p=0.01] while normal saline had no effect on the levels of sICAM-1, sE-Selectin and tPAI-1. Treatment with sildenafil was associated with increased perfusion in the ischemic limb compared with controls. CONCLUSION: Sildenafil exerts significant beneficial effects on tissue perfusion and inflammatory status after limb ischemia, a finding implying neovascularization and potential vascular protective properties of sildenafil.

Effects of direct infusion of bone marrow-derived progenitor cells and indirect mobilization of hematopoietic progenitor cells on atherosclerotic plaque and inflammatory process in atherosclerosis.

BACKGROUND: We sought to investigate the effects of lin-/sca+ cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression. METHODS: Apolipoprotein E-deficient (apoE(-/-)) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin-/sca-1+ cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups (n=10/group) and received two intravenous injections of 5×10(5) cells (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 µg/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed. RESULTS: The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94%±3.68, p=0.001), by lin-/sca-1+ (23.27%±5.98, p=0.002) and cultured EPCs (23.16±4.86%, p=0.002) compared to control (32.75%±7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group (p=NS, for all). CONCLUSIONS: Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin-/sca-1+, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.

Infusion of lin-/sca-1+ and endothelial progenitor cells improves proinflammatory and oxidative stress markers in atherosclerotic mice.

BACKGROUND: The effects of direct infusion or indirect mobilization of progenitor cells on atherosclerotic plaque development and progression are not clear. We sought to investigate the effects of hematopoietic progenitors lineage negative/stem cell antigen-1 positive (lin-/sca-1+) cells, endothelial progenitor cells and G-CSF administration on the inflammatory and oxidative component of atherosclerosis. METHODS: Splenectomized ApoE(-/-) C57BL/6J mice (6-8 weeks of age) fed with a high-fat, cholesterol-rich diet for 6 weeks, were divided in four groups (n=10/group) and received two intravenous injections of 5 × 10(5) cells (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 µg/kg/day) for 7 days or normal saline. sVCAM-1 (Vascular cell adhesion protein 1), sICAM-1 (soluble intercellular adhesion molecule-1), sE-Selectin, Metalloproteinase 9 (MMP-9), Plasminogen activator inhibitor (PAI-1), Interleukin 6 (IL-6), oxidized LDL (ox-LDL) levels and lipid PEROX were evaluated at the day of the first infusion, 7 days later and 6 weeks post-treatment with ELISA. RESULTS: The administration of both G-CSF and progenitor cells significantly decreased the levels of sICAM-1, sVCAM-1,sE-Selectin, IL-6, ox-LDL and lipid Perox 6 weeks after the initiation of treatment. No significant effects of lin-/sca-1+ cells, EPCs and G-CSF on PAI-1 and MMP-9 levels were observed. The effects of all treatments on the levels of pro-inflammatory molecules and oxidative stress parameters 7 days post-treatment were not significant. Interestingly, the levels of sICAM-1and sE-selectin were increased 7 days post-treatment. CONCLUSIONS: Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells significantly decreased the levels of proinflammatory molecules and oxidative stress parameters in a murine model of atherosclerosis. The principal novelty of this work is that treatment with hematopoietic progenitors, EPCs or G-CSF may exert beneficial effects on vascular inflammation and atherosclerotic plaque development.

Management of minor medical problems and trauma: the role of general practice.

INTRODUCTION: It has been established that patients prefer receiving health information from primary care physicians. In Greece, recent reforms supporting urban primary healthcare have not been enacted, and long waiting times in Athens' emergency departments are common. AIM: To evaluate cases treated in the emergency department of a Greek general hospital and explore the potential role of primary care in managing these cases. METHODS: A total of 53,926 patients visited the emergency department studied during on-call days from February 2005 to February 2006. The cases were classified into 6 groups according to their main complaint: (1) internal medicine; (2) surgical; (3) orthopedic; (4) otorhinolaryngology (ENT); (5) eye disorders (ophthalmology); and (6) gynecology-obstetric. RESULTS: Of the 53,926 patients studied, 9167 (17%) came from a rural area. The internal medicine department was most commonly attended (15,373; 28.5%), followed by orthopedics (16.9%). In the surgical, ENT, ophthalmology and gynecology groups, almost one in three patients could have been managed by a GP, as could 40% of orthopedic cases. Orthopedic and ENT patients had the highest rate of X-rays performed. CONCLUSION: Many emergency patients visiting hospitals can be managed at the primary care level. The development of a 'practice-based curriculum' for GPs would be an excellent method to obtain higher professional standards.