[InterAtrial Shunt Device in diastolic heart failure]. / InterAtrial Shunt Device bei diastolischer Herzinsuffizienz.

All types of heart failure are associated with reduced cardiac output and/or increased left atrial (LA) pressure. In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the increased LA pressure plays a central role, leading to pulmonary venous hypertension (PVH) and increased pulmonary artery pressure. These pressure parameters are presumably decisive for the symptoms and mortally of heart failure, particularly of the diastolic form. This is the basis for treatment with an interarterial shunt to reduce LA pressure in patients with diastolic heart failure and PVH. At first glance, this appears paradoxical, since closure of an atrial septum defect serves to prevent increased pulmonary vascular resistance and paradoxical embolism. Prevention of increased pulmonary vascular resistance and paradoxical embolism is thus an essential aspect in the development of devices for establishing an interarterial shunt. Reports on the InterAtrial Shunt Device (IASD®) and the V­Wave have been published, both of which can be implanted with a low risk and few complications. The V­Wave device is equipped with a valve to prevent paradoxical embolisms. However, paradoxical embolisms were also not observed with the IASD®, and the valve of the V­Wave exhibited considerable degenerative changes and valve closure. Hemodynamic and clinical data of patients with an IASD® or an open V­Wave device demonstrated a sustained hemodynamic improvement. Physical performance capacity and quality of life were increased. Whether IASD® may be broadly applicable in patients with diastolic heart failure is currently under investigation. In selected highly symptomatic patients with diastolic heart failure and PVH, the IASD® is already in clinal use.

[Diagnosis and treatment of aortic valve stenosis]. / Diagnose und Therapie der Aortenklappenstenose.

Aortic valve stenosis (AS) is the most frequently observed valvular heart disease. Once it is symptomatic the mortality rapidly increases. The diagnostic gold standard is transthoracic echocardiography. By measuring the maximum transvalvular velocity, mean transaortic pressure gradient and aortic valve opening area, classification of the type of stenosis can be defined. A differentiation is made between high-gradient AS, low-flow low gradient AS with reduced ventricular ejection fraction (<50%) and the paradoxical low-flow low-gradient AS with preserved ventricular function (≥50%). In some cases, additional diagnostic tools are necessary using dobutamine stress echocardiography, transesophageal echocardiography and cardiac computed tomography. The treatment follows an individualized approach. In cases of indications for valve replacement the multidisciplinary heart team takes into account the patient's age and individual risk for deciding whether an open surgical approach or transcatheter aortic valve implantation is indicated.

[New pharmaceuticals in cardiology. Heart failure, anticoagulation, dyslipidemia]. / Neue Medikamente in der Kardiologie. Herzinsuffizienz, Antikoagulation, Dyslipidämien.

Three innovative pharmaceuticals which might play an important role in the field of cardiology in the near future were recently tested in large clinical studies. Serelaxin, a vasoactive hormone peptide that is produced during pregnancy, reduces vessel resistance, increases cardiac output, and improves renal function. Lately, it was demonstrated that serelaxin significantly reduces congestion symptoms in patients with acute heart failure. As a secondary endpoint the mortality at day 180 was reduced. Therefore, serelaxin seems to be a promising new drug for the treatment of acute heart failure which might have a prognostic impact. Edoxaban is a selective factor Xa inhibitor, which inhibits thrombin production and thrombus formation. Two recently published studies reported that edoxaban is at least as effective as the vitamin K antagonist warfarin in prevention and treatment of venous thromboembolism and in the prevention of stroke and systemic embolism due to nonvalvular atrial fibrillation. Compared to warfarin, edoxaban significantly exhibited less frequent severe bleeding complications. Edoxaban will probably soon be the fourth new oral anticoagulant available for patients. The serine protease proprotein convertase subtilisin/kexin 9 (PCSK9) reduces the ability of the liver to bind low-density lipoprotein cholesterol (LDL-C) and to remove it from the circulation. Recently, a monoclonal antibody for PCSK9 was developed which induces a LDL-C plasma level reduction up to 73 % and also decreases lipoprotein(a) and apolipoprotein B. PCSK9 inhibition is a promising new mechanism for LDL-C reduction and the corresponding drug will be presumably approved soon by the regulatory authorities.

[Pathophysiology of chronic myocardial ischemia]. / Pathophysiologie der chronischen Myokardischämie.

Myocardial ischemia is caused by a mismatch between myocardial oxygen supply and myocardial oxygen requirements. Obstructive coronary artery disease (CAD) is the most common cause for myocardial ischemia. Although coronary bypass graft (CABG) surgery und percutaneous coronary interventions (PCI) are established therapies to treat CAD, 10 years after CABG or PCI 40% of the patients still have angina pectoris. Besides obstructive CAD, chronic myocardial ischemia can be induced by small vessel disease and endothelial dysfunction that is not treatable with CABG or PCI. On the cellular basis myocardial ischemia leads to a sodium overload that is caused by an increase in the late sodium current (I Na, late). The increased intracellular sodium concentration leads to a mode switch of the sodium/calcium exchanger (NCX) that now eliminates sodium from the cell and transports calcium into the cell. The resulting calcium overload activates the contractile myofilaments causing an increased wall tension in diastole which compromises the microcirculation and intensifies myocardial ischemia.

Midterm outcomes of LAA occlusion with the AMPLATZER Cardiac Plug and AMPLATZER Amulet devices in a high-risk cohort.

LAA occlusion has become a favourable option in patients with atrial fibrillation not eligible for oral anticoagulation therapy. Proof of effectiveness of LAA closure devices in a midterm follow-up period. This retrospective single-center cohort study analysed outcome in patients treated with AMPLATZER Cardiac Plug or AMPLATZER Amulet device. A standardized follow-up by phone call focusing on data of death, stroke and bleeding events was performed. Routine antiplatelet strategy was DAPT for 3 months post procedural. 212 patients (mean age 77 ± 6 years) were included. Follow up was performed in 197 (93%) patients. Patients were at high risk for thromboembolic or bleeding events (prior stroke/TIA 29%; prior bleeding 54%. Overall, there was a mean follow-up period of 1244.2 days (± 756.7) and a total of 674 patient years. We observed 25 events later than day 8 post procedure. We were able to demonstrate a high effectiveness of the AMPLATZER Cardiac Plug/AMPLATZER Amulet devices regarding the prevention of stroke and bleedings in a high-risk real-world cohort during a midterm follow-up period. Overall, we observed remarkably lower rates of stroke and bleedings as predicted with CHA2DS2-VASc and HASBLED scores.

MitraClip® and Amplatzer® cardiac plug implantation in a single procedure: A reasonable approach?

BACKGROUND: Percutaneous mitral valve repair using MitraClip® (MC) is a well-established method for a subset of patients with severe mitral regurgitation (MR) and high risk for surgical intervention. Amplatzer® Cardiac Plug (ACP) occludes left atrial appendage and allows the discontinuation of oral anticoagulation and prevention of thromboembolic stroke. Due to the need for femoral and transseptal access in both procedures, a single approach could lead to minor risk of further complications and shorter cumulative intervention time. METHODS: We systematically analysed all four patients who underwent a combined procedure with MC and ACP in our heart-centre. All procedures were performed under fluoroscopic as well as echocardiographic guidance, and follow-up controls in a midterm period were carried out. RESULTS: In all patients (2 male/female; age 73-88years), MC (1-2 Clips) and ACP (size 18-28mm) were successfully implanted in one procedure (mean total time: 114±17min). At least moderate MR was achieved and two patients had no complications and therefore were discharged early. In a third patient, a dislocation of ACP occurred 2h after the implantation. The oldest patient developed a respiratory insufficiency due to cardiac decompensation and further complications. CONCLUSION: A combination of MC and ACP in a single procedure was feasible in this first case series of patients without a significant extension of procedure time. However, it might be important to select patients carefully. The location of optimal transseptal puncture may be challenging in regard to ACP placement, even in experienced hands and subsequent complications can occur.

[Insufficient use of anticoagulants in geriatric in-patients with atrial fibrillation and flutter (corrected)]. / Hospitalisierte geriatrische Patienten mit Vorhofflimmern sind nicht ausreichend mit Antikoagulanzien behandelt.

INTRODUCTION: Anticoagulation for the prevention of cardioembolic events is highly effective, but largely underused in frail older patients with atrial fibrillation or flutter (AF). This study aimed at identifying characteristics associated with anticoagulation use or non-use and the most frequent complications of this therapy. METHODS: Hospitalized geriatric patients treated in a one-year interval were retrospectively studied for the presence of AF and use or non-use of anticoagulation. The risk of stroke and the indication for permanent anticoagulation were assessed using the CHA2DS2-VASc score. RESULTS: In 451 of 1167 hospitalized patients (38.6%) there was a clear indication for anticoagulation. The most frequent indication for anticoagulation was AF in 381 patients (84.5% of 451 patients). Of these 381 patients, a strong indication for anticoagulation, based on CHA2DS2-VASc score, was identified in 379 patients. Of these patients, 200 (52.8%) did and 179 (47.2%) patients did not receive anticoagulation. 153 patients (40.4%) received antiplatelet therapy. 26 patients (6.7%) received neither anticoagulants nor antiplatelet therapy. The most common reason for non-implementation of anticoagulation was a high risk of falls in 93 patients (52%) of 179 patients without antocoagulation. The most frequent complications of anticoagulation were small hemorrhages without serious consequences in 8 cases. 4 patients suffered from serious bleedings. CONCLUSION: Almost half of our geriatric population did not receive anticoagulation despite a clear indication. Antiplatelet therapy use was associated with anticoagulation non-use.

[Diabetes increases short- and long-term mortality after transcatheter aortic valve implantation (TAVI)]. / Diabetes mellitus erhöht die eingriffsbedingte und die langfristige Mortalität nach kathetergestützter Aortenklappenimplantation.

BACKGROUND AND AIM: Long-term mortality after transcatheter aortic valve implantation (TAVI) in elderly patients with abundant comorbidities is considerable. We aimed to determine the impact of diabetes on short- and long-term mortality after TAVI. METHODS: Our study includes 300 consecutive patients (mean age, 82 ± 5 years) who underwent TAVI (158 transapical, 142 transfemoral procedures). All patients were followed by regular telephone contacts. 36% suffered from diabetes. RESULTS: Diabetes could be identified as significant predictor of short- and long-term mortality after TAVI. In diabetic patients, 30-day-mortality was 2,5 fold elevated (18.3% vs. 7.3%, p = 0.004). Furthermore, they were at significantly higher risk of peri-interventional stroke (p = 0.04), stage 3 acute kidney injury (p = 0.003), and prolonged ventilation (p = 0.01). Even after successful TAVI and discharge from hospital, long-term mortality was significantly elevated in diabetic patients (56% vs. 30%, p < 0.0001). Of note, 25% of diabetic vs. only 8% of non-diabetic patients died from cardiac causes during follow-up, suggesting that TAVI is not able to reduce cardiac-related mortality risk in diabetic patients to the same extent as in non-diabetics. CONCLUSION: Diabetes represents a powerful predictor of adverse early and late outcome after TAVI. These findings should be incorporated into the assessment of the risk-to-benefit ratio of TAVI in diabetic patients.

Hotline update of clinical trials and registries presented at the American College of Cardiology Congress 2010: ACCORD, INVEST, NAVIGATOR, RACE II, SORT OUT III, CSP-474, DOSE, ASPIRE and more.

This article gives an overview on a number of novel clinical trials in the field of cardiovascular medicine, which were presented during the Late Breaking Clinical Trial Sessions at the 59th annual meeting of the American College of Cardiology in Atlanta, USA, from 14th March to 16th March 2010. The data were presented by leading experts in the field with relevant positions in the trials. These comprehensive summaries should provide the readers with the most recent data on diagnostic and therapeutic developments in cardiovascular medicine similar as previously reported (Schirmer SH, van der Laan AM, Bohm M, Mahfoud F in Clin Res Cardiol 98:691-699, 2009; Maier LS, Schirmer SH, Walenta K, Jacobshagen C, Bohm M in Clin Res Cardiol 98:413-419, 2009).

Hotline update of clinical trials and registries presented at the German Cardiac Society Meeting 2009.

This review article gives an overview on a number of novel clinical trials and registries in the field of cardiovascular medicine. Key presentations made at the 75th annual meeting of the German Cardiac Society, held in Mannheim, Germany, in April 2009 are reported. The data were presented by leading experts in the field with relevant positions in the trials and registries. These comprehensive summaries should provide the readers with the most recent data on diagnostic and therapeutic developments in cardiovascular medicine similar as previously reported (Rosenkranz et al. in Clin Res Cardiol 96:457-468, 9; Maier et al. in Clin Res Cardiol 97:356-363, 3).

Extracellular nucleotides regulate cellular functions of podocytes in culture.

Extracellular nucleotides are assumed to be important regulators of glomerular functions. This study characterizes purinergic receptors in podocytes. The effects of purinergic agonists on electrophysiological properties and the intracellular free Ca(2+) concentration of differentiated podocytes were examined with the patch-clamp and fura 2 fluorescence techniques. mRNA expression of purinergic receptors was investigated by RT-PCR. Purinergic agonists depolarized podocytes. Purinergic agonists similarly increased intracellular free Ca(2+) concentration of podocytes. The rank order of potency of various nucleotides on membrane voltage and free cytosolic calcium concentration was UTP approximately UDP > [adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S)] > ATP > 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) > 2'- and 3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP) > ADP-beta-S. alpha,beta-Me-ATP was without effect. In the presence of UTP, BzATP did not cause an additional depolarization of podocytes. Incubation of cells with ATP or BzATP did not induce lactate dehydrogenase release. In RT-PCR studies, mRNAs of the P2Y(1), P2Y(2), P2Y(6), and P2X(7) receptors were detected within glomeruli and podocytes. The data indicate that extracellular nucleotides modulate podocyte function mainly by an activation of both P2Y(2) and P2Y(6) receptors.