Heartdrug : excellence in cardiovascular trials最新文献

{"title":"Potassium Must Be Considered in Congenital Long QT Syndrome","authors":"M. Christiansen, K. Kjeldsen, G. Wettrell, L. Larsen, L. Lundkvist, P. Andersen, C. T. Tran, J. Kanters, J. Vuust","doi":"10.1159/000083388","DOIUrl":"https://doi.org/10.1159/000083388","url":null,"abstract":"Background: Congenital long QT syndrome (cLQTS), characterized by prolonged QTc time, syncope or sudden death caused by torsade de pointes ventricular tachycardia, has an autosomal dominant pattern of inheritance and is caused by mutations in genes coding for the cardiac ion channels conducting the depolarizing sodium current, INa, and the repolarizing delayed rectifier potassium currents, IKr and IKs. Methods: We describe a family in which one family member died suddenly and unexpectedly from what was assumed to be cardiac death, and in which another person with symptoms indicating cLQTS had been controlled for more than 40 years with oral potassium chloride and ammonium chloride. She was screened for mutations in LQTS genes using polymerase chain amplification reaction of genomic DNA followed by single-strand conformation polymorphism analysis. Results: A clinically well-described missense mutation, G306R in KCNQ1, coding for the ion channel conducting the IKs current was found. The mutation causes a moderately dominant reduction in the IKs current. Conclusion: The novel observation is that potassium in cLQTS caused by the KCNQ1 mutation protects against syncope in a life-long perspective. Thus, although the mechanism is not fully elucidated, maintaining a normal potassium homeostasis is of general importance. Hence, securing sufficient intake of potassium and careful control of potassium-losing conditions are important elements in the management of patients with cLQTS as a supplement to established therapeutic strategies.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"18 1","pages":"54 - 58"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65271192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Efficacy of Ivabradine","authors":"J. Tardif","doi":"10.1159/000083383","DOIUrl":"https://doi.org/10.1159/000083383","url":null,"abstract":"Ivabradine is the first selective and specific If inhibitor with a complete clinical development program. This new pharmacological class represents a novel approach to heart rate reduction that could be of special relevance in different clinical situations such as stable angina. Ivabradine was shown to reduce resting heart rate without modifying any major electrophysiological parameters. Thus, exclusive heart rate reduction can be achieved in the clinic as a result of specific and selective If current inhibition. Ivabradine efficacy has been evaluated in a large clinical program in stable angina. This article will present the results of four randomized clinical studies which have evaluated the efficacy of ivabradine in stable angina patients. Ivabradine was shown to be superior to placebo in improving exercise tolerance test (ETT) criteria (n = 360). In a 4-month, double-blind, controlled study (n = 939), ivabradine 5 and 7.5 mg twice daily was shown to be at least as effective as atenolol 50 and 100 mg once daily. Furthermore, the anti-ischemic and antianginal efficacy of ivabradine has been demonstrated versus amlodipine (n = 1,195), improving total exercise duration and other ETT criteria, and reducing the frequency of angina attacks. Additionally, ivabradine maintains its antianginal efficacy in the long term. Ivabradine therefore represents a valuable treatment for patients with stable angina.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"25 - 28"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65270192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lowering LDL Cholesterol: Where Is the End of the Journey?","authors":"W. März","doi":"10.1159/000083386","DOIUrl":"https://doi.org/10.1159/000083386","url":null,"abstract":"Lowering LDL cholesterol (LDL-C) with statins is a well-documented strategy to reduce the incidence rate of cardiovascular events and deaths. There has been consensus so far that LDL-C should at least be lowered to 100 mg/dl in individuals suffering from established atherosclerotic disease and/or diabetes mellitus. Results of recent intervention trials of highly effective statins have lead to suggest that the target for high-risk individuals be set at substantially lower concentrations. As demonstrated by the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study this recommendation appears warranted particularly in patients with acute coronary syndromes. However, evidence is emerging that LDL-C levels well below 100 mg/dl would also produce significant additional clinical benefit in patients with stable coronary artery disease or type 2 diabetes.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"39 - 50"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65270622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Educational Autumn Meeting on Advances in Cardiovascular Drug Therapy","authors":"K. Stoschitzky","doi":"10.1159/000083377","DOIUrl":"https://doi.org/10.1159/000083377","url":null,"abstract":"In the present issue of Heart Drug you will fi nd nine proceedings condensed from the Educational Autumn Meeting on Advances in Cardiovascular Drug Therapy, organized by the Working Group on Cardiovascular Pharmacology and Drug Therapy of the European Society of Cardiology in Vienna, Austria, November 27–28, 2004. The following topics were presented and discussed at our Educational Autumn Meeting: Are all -blockers equal?, Advances in the treatment of hyperlipidemia, and I f current inhibition. There were three lectures on each of these topics given by distinguished experts in their fi elds who also wrote the respective papers in this issue of Heart Drug . I hope you will enjoy reading these proceedings on these exciting topics! Kurt Stoschitzky Published online: January 19, 2005","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"1 - 1"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65269879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacology of If Current Inhibition","authors":"V. Benatar, G. Lerebours Pigeonnière, Patricia Nury-Philémon","doi":"10.1159/000083382","DOIUrl":"https://doi.org/10.1159/000083382","url":null,"abstract":"Elevated resting heart rate is linked to an increase in both cardiovascular and all-cause mortality, and agents that reduce heart rate have obvious applications in improving the prognosis of coronary artery disease and heart failure. In this short review, we examine the pathophysiological grounds for the original clinical benefits of pure heart rate lowering through the development of a new class of heart-rate-reducing agents. Ivabradine, a novel selective and specific inhibitor of the If pacemaker current in the sinoatrial node cells, is the prototype of this pharmacological class. It has shown anti-ischemic and antianginal efficacy superior to placebo and comparable to β-blockers and calcium channel blockers. In early clinical pharmacological studies, ivabradine was shown to reduce heart rate in a dose-dependent manner without modifying other cardiac parameters such as conduction, contractility, and ventricular repolarization. Ivabradine improves myocardial oxygen delivery and decreases oxygen consumption. Together, these properties make ivabradine a valuable alternative to existing drug therapies for stable angina and other myocardial conditions.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"21 - 24"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65269952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the Basic Pharmacology of Beta-Blocking Agents","authors":"M. Wehling","doi":"10.1159/000083378","DOIUrl":"https://doi.org/10.1159/000083378","url":null,"abstract":"β-Blockers are important in the treatment of arterial hypertension, coronary heart disease, cardiac arrhythmias and heart failure. Their effects are mediated by the blockade of various types of β- and α-receptors, and compounds have been developed to specifically inhibit them. Nonselective β-blockers (e.g. propranolol, nadolol, penbutolol and carvedilol) differ from β1-selective blockers (e.g. metoprolol, atenolol, bisoprolol and nebivolol). Selectivity is never absolute and all β-blockers can cause problems in allergic asthma including serious side effects and death. The clinical advantage of selectivity appears to be meager, as only few patients with chronic obstructive pulmonary disease seem to benefit from increased tolerability. Another important feature is the intrinsic-sympathomimetic activity of some compounds (e. g. pindolol or oxprenolol), which is associated with negative outcomes. Vasodilation by additional α-blockade as seen with carvedilol results in metabolic neutrality and superior tolerability especially in patients with hypertension, heart failure and pAVK. Nebivolol is a β-blocker which leads to NO generation in the endothelium, and, thus, to NO-dependent vasodilation, and thus has a strong antihypertensive profile.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"2 - 5"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65270046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Era of Statins – Is There Still a Place for Other Classes of Lipid-Lowering Drugs?","authors":"T. Wascher","doi":"10.1159/000083385","DOIUrl":"https://doi.org/10.1159/000083385","url":null,"abstract":"Plenty of evidence suggests statins as the first-line therapy for the treatment of lipid disorders. However, further therapeutic options available in the treatment of lipid disorders are fibrates, niacin and cholesterol absorption inhibitors. In the present study, current treatment modalities of lipid disorders are reviewed, and their use was scrutinized based on the available evidence.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"34 - 38"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65270440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Additional Features of Beta-Blockers","authors":"K. Stoschitzky","doi":"10.1159/000083379","DOIUrl":"https://doi.org/10.1159/000083379","url":null,"abstract":"The predominant action of β-blockers is their inhibition of the stimulating effects of adrenaline and noradrenaline on sympathetic β-adrenoceptors. In this context, they are particularly useful in the treatment of arterial hypertension, coronary artery disease, myocardial infarction, tachyarrhythmias and heart failure. However, a number of β-blockers also exert additional effects independent from the inhibition of β-receptors: nebivolol causes NO-derived vasodilation, carvedilol also inhibits sympathetic α-receptors, sotalol shows additional antiarrhythmic class III effects, and propranolol inhibits the conversion of thyroxine to triiodothyronine and shows slight antiarrhythmic class I effects. In addition, β-blockers may be used in the treatment of other diseases such as hyperthyroidism, migraine, essential tremor, portal hypertension, hypertrophic obstructive cardiomyopathy and aortic dissection. As a special feature, most β-blockers are taken up into, stored in and released from adrenergic cells together with adrenaline and noradrenaline. Consequently, plasma concentrations of these drugs are markedly increased during exercise together with those of adrenaline and noradrenaline and remaining β-blocking effects long after the withdrawal of chronic administration of β-blockers, even when they are no longer detectable in plasma. Furthermore, except for nebivolol and carvedilol, all β-blockers investigated in this context inhibit the nocturnal production and release of melatonin. Finally, all β-blockers currently used in the treatment of cardiovascular diseases are racemic mixtures consisting of (R)- and (S)-enantiomers in a fixed 1:1 ratio although they may show different pharmacokinetics, and only the (S)-enantiomers cause β-blockade whereas the (R)-forms do not contribute to this effect but may increase side effects and drug interactions. Thus, β-blockers may exert a number of interesting features in addition to their well-known effects on cardiac β-adrenoceptors.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"6 - 10"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65270063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium in Long QT Syndromes","authors":"S. Kääb","doi":"10.1159/000083387","DOIUrl":"https://doi.org/10.1159/000083387","url":null,"abstract":"fects are mediated mostly by the rapidly activating delayed rectifi er potassium current (I Kr ) that is paradoxically increased when extracellular potassium is increased [9] . When KCNH2, the gene coding for the -subunit of I Kr , was fi rst linked to the congenital long QT syndrome, the cornerstone for gene-specifi c therapy was laid [10] . Compton et al. [11] where the fi rst to systematically study the effects of potassium supplementation in patients with congenital long QT syndrome. They showed that acute intravenous potassium supplementation (increase 6 1.5 mEq/l) led to a 24% reduction in QTc in 7 patients carrying mutations in KCNH2 (LQT2) compared to a 4% reduction in 5 control probands [11] . This study was followed by a recent study testing a 4-week oral potassium administration (accompanied by high-dose spironolactone) in 8 patients with mutations in KCNH2 that demonstrated an increase in serum potassium from 4.0 8 0.3 to 5.2 8 0.3 mEq/l resulting in a decrease in QTc from 526 8 94 to 423 8 36 ms [12] . In this issue of Heart Drug , Christiansen et al. [13] report the case of a female patient that had been resuscitated several times at the age of 5–6 years while bathing at the beach. She had experienced several syncopal events at the age of 35 when ECG revealed broad T and U waves, and had been treated successfully with potassium salts and ammonium chloride for more than 35 years until she was diagnosed with a known mutation in KCNQ1 (G306R) that has been found to exhibit a dominant negLong QT syndrome is considered as a genetically heterogeneous disease caused by defects predominantly in genes coding for myocardial ion channels with a natural history ranging from sudden death in infancy to asymptomatic longevity [1] . Congenital long QT syndrome serves as a model disease for understanding arrhythmogenesis in the context of altered repolarization. Besides mutations that directly affect cardiac repolarization, a number of additional factors, e.g. female gender, left ventricular hypertrophy, and heart failure, drugs, and hypokalemia have been linked to QT prolongation and risk of arrhythmias. The concept of reduced repolarization reserve as the basis for individual susceptibility to arrhythmias in the context of QT prolongation [2] has been confi rmed in several studies [3, 4] and applies for the congenital long QT syndrome as well as for other causes of QT prolongation, e.g. hypertrophy, heart failure and QT-prolonging drugs. Current evidence suggests that reduced repolarization reserve is caused by mutations in disease genes (familial LQTS) and may be subclinical until unmasked by extrinsic triggers (e.g. drugs and hypokalemia) [5] . Potassium has been linked to cardiac arrhythmias for almost a century, and its effects on the QT interval have been previously shown. Potassium supplementation may have arrhythmia-suppressing properties [6, 7] and the potential mechanism being the shortening of cardiac action potentials [8] . Today, it is","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"51 - 53"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65271394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Relevance of Differences between Various Beta-Blockers","authors":"M. Vintila","doi":"10.1159/000083380","DOIUrl":"https://doi.org/10.1159/000083380","url":null,"abstract":"More than 15 beta-blockers are available today. They represent a class I recommendation in major cardiovascular disorders such as hypertension, coronary heart disease and chronic heart failure. If in hypertension and coronary heart disease their favorable action is considered a class effect, in heart failure some of them are of more benefit than others. Bisoprolol, carvedilol and metoprolol proved in important clinical trials significant reductions in mortality and morbidity in patients with different stages of heart failure, from asymptomatic ventricular dysfunction to NYHA class IV heart failure. The newcomer nebivolol reduced morbi-mortality in old and very old patients as shown in the recently presented SENIORS study.","PeriodicalId":87985,"journal":{"name":"Heartdrug : excellence in cardiovascular trials","volume":"5 1","pages":"11 - 13"},"PeriodicalIF":0.0,"publicationDate":"2005-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000083380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65270114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}