Rapid and MR-Independent IK1 activation by aldosterone during ischemia-reperfusion

In ST elevation myocardial infarction (STEMI) context, clinical studies have shown the deleterious effect of high aldosterone levels on ventricular arrhythmia occurrence and cardiac mortality. Previous in vitro reports showed that during ischemia-reperfusion, aldosterone modulates K+ currents involved in the holding of the resting membrane potential (RMP). The aim of this study was to assess the electrophysiological impact of aldosterone on IK1 current during myocardial ischemia-reperfusion. We used an in vitro model of “border zone” using right rabbit ventricle and standard microelectrode technique followed by cell-attached recordings from freshly isolated rabbit ventricular cardiomyocytes. In microelectrode experiments, aldosterone (10 and 100 nmol/L, n=7 respectively) increased the action potential duration (APD) dispersion at 90% between ischemic and normoxic zones (from 95±4ms to 116±6 ms and 127±5 ms respectively, P<0.05) and reperfusion-induced sustained premature ventricular contractions occurrence (from 2/12 to 5/7 preparations, P<0.05). Conversely, potassium canrenoate 100 nmol/L and RU 28318 1 μmol/l alone did not affect AP parameters and premature ventricular contractions occurrence (except Vmax which was decreased by potassium canrenoate during simulated-ischemia). Furthermore, aldosterone induced a RMP hyperpolarization, evoking an implication of a K+ current involved in the holding of the RMP. Cell-attached recordings showed that aldosterone 10 nmol/L quickly activated (within 6.2±0.4 min) a 30 pS K+-selective current, inward rectifier, with pharmacological and biophysical properties consistent with the IK1 current (NPo =1.9±0.4 in control vs NPo=3.0±0.4, n=10, P<0.05). These deleterious effects persisted in presence of RU 28318, a specific MR antagonist, and were successfully prevented by potassium canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp recordings, thus indicating a MR-independent IK1 activation. In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation

Comparison of outcomes in patients with abandoned versus extracted implantable cardioverter defibrillator leads

SummaryBackgroundDespite the increased number of implantable cardioverter defibrillator (ICD) recipients and the frequent need for device upgrading and/or occurrence of lead malfunction, the optimal approach to managing abandoned leads remains debated. Aims To determine the rate and type of complications related to either abandoned or extracted ICD leads. Methods Patients with abandoned or extracted leads were identified retrospectively. Patient medical records were reviewed to assess long-term lead or device malfunction, defibrillation test values before and after lead abandonment or extraction, and appropriateness of delivered shocks and subsequent surgical procedures related to devices or leads. Results A total of 58 ICD patients with 47 extracted and 34 abandoned leads were identified. After a mean follow-up of 3.2 ± 2.6 years, the defibrillation test was not affected by either abandoned or extracted leads (23.4 ± 6.6 J vs 25.4 ± 4.9 J, respectively; P = 0.24). There were no differences in the number of ICD-related surgical procedures after extracting versus abandoning leads (22% vs 12%, respectively; P = 0.3) or in the thromboembolic event rate (7.7% vs 6.3%; P = 0.83). During follow-up, no differences in the occurrence of major complications or appropriate/inappropriate shocks were observed between patients with or without abandoned leads. Conclusion We observed no difference in rates of immediate or medium-term complications between extracting versus abandoning leads. Lead abandonment remains an alternative and safe option when extraction does not appear mandatory according to the age of the leads or experience of the operating centre

Conduction disturbances in Tako Tsubo cardiomyopathy: A cause or a consequence?

Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy mimicking acute myocardial infarction characterized by a transient left ventricular (LV) apical ballooning without epicardial coronary artery disease [1]. Most remarkable is the complete reversibility of this cardiomyopathy resolving spontaneously within several weeks [1]. Conduction pathway disorders were rarely associated with TTC. We described two cases of TTC with conduction disorders persisting after improvement of left ventricular wall motion that finally motivated the implantation of pacemakers

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).&lt;p&gt;&lt;/p&gt; Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.&lt;p&gt;&lt;/p&gt; Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.&lt;p&gt;&lt;/p&gt; Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.&lt;p&gt;&lt;/p&gt

Primary prevention with a defibrillator: are therapies always really optimized before implantation?

AIMS:Left ventricle ejection fraction (LVEF) ≤ 30-35% is widely accepted as a cut-off for primary prevention with an implantable cardiac defibrillator (ICD) in patients with both ischaemic and non-ischaemic cardiomyopathy supposedly on optimal medical therapy. This study reports evolutions of LVEF and treatments of patients implanted in our institution with an ICD for primary prevention of sudden death, after 2 years of follow-up. METHODS AND RESULTS: Among 84 patients with LVEF under 35% implanted between 2005 and 2007, 28 (33%) had improved their LVEF &gt;35% after the 2 years of follow-up. During this period, even if Beta-blockers (98%) and renin-angiotensin system (RAS) blockers (95%) were already initially prescribed, treatments were significantly optimized with improvement of maximal doses of beta-blockers and RAS blockers at 2 year follow-up compared with initial prescription (62 vs. 37% and 68 vs. 45%, respectively). In patients with improved LVEF, a trend toward a better treatment optimization and revascularization procedures (in the sub-group of ischaemic patients) were observed compared with non-improved LVEF patients. CONCLUSIONS: In our study of patients with prophylactic ICD, one-third of them have improved their LVEF after a 2 year follow-up. Despite an optimal medical therapy at the time of implantation, we were able to further improve the maximal treatment doses after implantation. This study highlights the issue of what should be considered as \u27optimal\u27 therapy and the possibility of improvement of LVEF related to a real optimized treatment before implantation

A rare localization in right-sided endocarditis diagnosed by echocardiography: A case report

BACKGROUND: Right-sided endocarditis occurs predominantly in intravenous drug users, patients with pacemakers or central venous lines and with congenital heart diseases. The vast majority of cases involve the tricuspid valve. CASE PRESENTATION: A case of a 31-year-old woman with intravenous drug abuse who had a right-sided vegetation attached to the muscular bundle of the right ventricle is presented. Transthoracic echocardiography revealed a vegetation in the right ventricular outflow tract. Transesophageal echocardiography clearly showed that the 1.8 cm vegetation was not adherent to the pulmonary valve but attached to a muscular bundle. CONCLUSIONS: Our case points to an unusual location of right-sided endocarditis in intravenous drug users. It confirms that TTE remains an easy and highly sensitive first-line examination for the diagnosis of right-sided endocarditis

Primary aldosteronism: A Japanese perspective

Primary aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 10% of all hypertension. Far from being benign, hypertension due to PA is associated with high cardiovascular morbidity and mortality. However, PA is still underdiagnosed in general practice. Recent reports strongly recommend that identifying patients with PA is cost-beneficial based on improved cardiovascular outcomes afforded by specific surgical and medical treatment. This review provides an update of PA including controversial aspects of diagnosis and treatment

Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism

<p>Abstract</p> <p>Background</p> <p>Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.</p> <p>Methods and design</p> <p>In this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR) as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT) as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL) who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin.</p> <p>Conclusion</p> <p>Screening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.</p