Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

BACKGROUND: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).

Pacemaker ECG with the Littmann sign.

Severe hyperkalemia may be concealed in the electrocardiogram (ECG). We present the case of a critically ill patient with severe bradycardia and the BRASH syndrome. In critically ill patients, double counting of the heart rate is frequently a marker of severe hyperkalemia (Littmann sign). In our case, hyperkalemic double counting only appeared in the ECG performed during percutaneous pacing. The Littmann sign helped with the early recognition of hyperkalemia and the BRASH syndrome.

Pseudo precordial ST-segment depression.

We present a case with acute coronary syndrome and very unusual QRS widening in the acute phase. The case highlights that non-specific intraventricular conduction delay should be considered as a high risk ECG pattern predicting poor prognosis.

A puzzling overnight change in the QRS morphology.

Pacemakers set in a bipolar pacing mode often result in no discernible spikes on surface 12­lead ECG registrations. In this situation, left axis deviation combined with wide QRS can help to identify the paced ECG morphology. We present a case of a non-pacemaker dependent patient whose normal atrioventricular conduction also appeared as atypical left axis deviation with wide QRS on the ECG. These two depolarization-repolarization morphologies, and the switch between the two raised differential diagnostic questions. The case also illustrates a paced ECG demonstrating the concept of Littmann: a close relationship between leads V2 and aVL.

Precordial ST-segment continuum: A variant of the de Winter sign.

The vast majority of patients with acute occlusion of the proximal left anterior descending coronary artery (LAD) suffer frank ST-elevation myocardial infarction (STEMI). In contrast, a small but not insignificant minority presents with an electrocardiographic (ECG) pattern termed the "de Winter sign." The de Winter sign is characterized by upsloping ST depression followed by tall and peaked T waves in the precordial leads. The purpose of this report is to present two cases of acute obstruction of a large wrap-around LAD where the ECGs simultaneously displayed diagnostic criteria both for STEMI and the de Winter sign. We provide possible explanations for this hitherto undescribed phenomenon.

WITHDRAWN: My favorite ECG displaying the Wellens syndrome: In memoriam Hein Wellens.

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Peri-infarction block, a marker for VT risk?

We present a monomorphic ventricular tachycardia (VT) in a patient with a history of myocardial infarction and syncope. The ECG shows an acceleration-dependent peri-infarction block inferiorly. The authors suggest that this old (but forgotten) ECG-entity may serve as a marker for assessing the risk of post-infarction VT.

Narrow QRS complexes within left bundle branche block in a patient with chest pain.

We present the case of a patient with chest pain, palpitations, atrial fibrillation, left bundle branch block (LBBB) and occasional early narrow QRS complexes. An intracardiac study revealed rate-dependent LBBB with additional hidden rate-dependent slowing in the contralateral bundle branch, resulting in normalization of the early conducted QRS complexes.

Syncope due to unexpected paroxysmal sinus arrest.

We present two cases with unexpected long sinus arrest resulting in syncope. There were no signs or symptoms of either sick sinus syndrome or increased vagal tone before the occurrence of pauses in these patients. The fact that these patients remained asymptomatic for quite long shows striking resemblance to paroxysmal sub-AV nodal block. We would therefore prefer to classify these cases as paroxysmal sinus arrest as a possible manifestation of the sick sinus syndrome.

Link between Brugada phenocopy and myocardial ischemia: Results from the International Registry on Brugada Phenocopy.

BACKGROUND: Brugada phenocopies clinical entities that have indistinguishable electrocardiographic (ECG) patterns from true congenital Brugada syndrome. However, they are induced by other clinical circumstances such as myocardial ischemia. The purpose of our study was to examine the clinical features and pathogenesis of ischemia-induced Brugada phenocopy (BrP). METHODS: Data from 17 cases of ischemia-induced BrP were collected from the International Registry (www.brugadaphenocopy.com). Data were extracted from these publications and authors were contacted to provide further insight into each case. RESULTS: Of the patients included in this study, 71% were male. Mean age was 59 ± 11 years (range: 38-76). Type-1 Brugada ECG pattern occurred in 15/17 (88%) of the cases, while a type-2 Brugada ECG pattern was observed in the other 2/17 (12%). In all cases, the Brugada ECG pattern resolved upon correction of the ischemia, indicating ischemia as the inducing circumstance. No arrhythmic events have been detected acutely or during the follow-up. Reported time to resolution ranged from 2 minutes to 5 hours. Provocative challenges using sodium channel blocking agents were performed in 7/17 cases (41%), and all failed to induce a Brugada ECG pattern (BrP Class A). The remaining 10/17 cases (59%) did not undergo provocative testing due to various clinical reasons. CONCLUSIONS: Myocardial ischemia is a commonly reported etiology of BrP. Importantly, this study found no association between BrP induced by myocardial ischemia and sudden cardiac death or malignant ventricular arrhythmias.

[ECG pearl: the Brugada sign. Case report]. / EKG-gyöngyszem: a Brugada-jel.

An Asian patient was admitted with palpitation. The ECG showed coved-shaped type Brugada pattern with QRS-fragmentations. Early recognition and risk stratification are the most important issues in Brugada syndrome. Orv Hetil. 2018; 159(45): 1848-1850.

[ECG pearls: Pseudoinfarct Q waves and low voltage]. / EKG-gyöngyszem: Pseudoinfarctusos Q-hullámok és alacsony kilengések.

Therapy refracter heart failure is presented. The admission ECG shows low voltage and pseudoinfarct Q waves highly diagnostic for the etiology of heart failure. Orv Hetil. 2018; 159(8): 327-329.

[Interatrial block and its clinical relevance. Renaissance of an ECG change]. / Az interatrialis blokk és klinikai jelentosége. Egy EKG-entitás reneszánsza.

Interatrial block involves conduction delay between the right and left atria during sinus rhythm. The review describes the classification, pathomechanism and clinical significance of this under-recognised ECG sign, nominated Bayés syndrome. The presented ECGs help to recognise the differentypes of interatrial blocks. Orv Hetil. 2018; 159(3): 91-95.

[ECG pearl: transient Q-waves in myocardial infarction]. / EKG-gyöngyszem: tranziens Q-hullám myocardialis infarctusban.

A case of ST-segment elevation myocardial infarction (STEMI) is presented with pathologic transient Q-waves in the precordial leads disappearing after percutaneous coronary intervention (PCI). Orv Hetil. 2018; 159(29): 1208-1209.

[Effectiveness of trimetazidine prolong in stable coronary artery disease. Multicenter, prospective, observational study, ONECAPS study]. / Stabil coronariabetegség kezelésére alkalmazott trimetazidin prolong hatásosságának vizsgálata. Multicentrikus, prospektív, obszervációs, nyílt klinikai vizsgálat, ONECAPS-vizsgálat.

INTRODUCTION: The effectiveness of the manegement of stable coronary artery disease among outpatients is not well known. AIM: The aim of the study was to evaluate the effect of daily once trimetazidine prolong 80 mg on the angina number and severity (Canadian Cardiovascular Society class). METHOD: This multicenter, prospective, observational, 3-month clinical study included 2160 patients, but only 1701 patients completed the study. The patients' mean age was 68 years (17% under 60 years). The start of angina was 7.8 ± 6.7 years. Hypertension (93.4%) and hypercholesterolemia (81%) were very common. RESULTS: The patients were well treated with beta-blocking agents (88%), calcium antagonists (49%), angiotensin-converting enzym inhibitors (90%) and statin (77%) but only 5% received ivabradine and 50.5% was treated with trimetazidine MR. The patients attended 3 visits (inclusion, 1 month, 3 month). During the 3-month period, the weekly angina number of all patients treated with trimetazidine prolong 80 mg decreased from 2.55 to 0.41 (p<0.0001). A favorable effect was observed in CCS grading: CCS I. from 40.37% to 66.81%, CCS II. from 49.89% to 30.59%, CCS III. from 9.17% to 2% and CCS IV. from 0.56% to 0%. The mean office measured blood pressure decreased from 137/83 mmHg to 130/80 mmHg and the heart rate from 74 bpm to 71 bpm. CONCLUSIONS: In the real-life, in the stable coronary artery disease the angina remains despite the medical treatment. Once a day administered trimetazidine prolong 80 mg significantly reduced the weekly number of angina and the severity, too. These beneficial effects mediated not only by antiischemic effect but also by increased medication adherence. Orv Hetil. 2018; 159(38): 1549-1555.

[ECG pearl: acquired long QT syndrome]. / EKG-gyöngyszem: szerzett hosszú-QT-szindróma.

Authors report the case of a patient with drug-induced long QT syndrome. This case highlights the importance of ECG signs of LQTS that may lead to torsade de pointes tachycardia. The patient received the QT prolonging moxifloxacine and the QT remained long even after the offending drug was discontinued. Orv Hetil. 2018; 159(39): 1607-1610.

[The value of early repeated N-terminal pro-B-type natriuretic peptide measurement in acute heart failure]. / Az N-terminális pro-B natriureticus peptid mérésének korai ismétlése akut szívelégtelenség miatt hospitalizált betegeken.

INTRODUCTION: The determination of natriuretic peptide levels in patients hospitalized for suspected acute heart failure is important for the confirmation of the diagnosis and for the prognosis. Changes in natriuretic peptide levels in response to therapy have a strong prognostic value. AIM: To decide whether repeated natriuretic peptide measurements for acute heart failure show changes that could influence the diagnosis and/or the prognosis. METHOD: Prospective data collection was carried out of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels on admission and within 12 hours in patients hospitalized for acute heart failure. Only the data of those patients were analyzed whose symptoms started within 24 hours prior to admission and were due to acute heart failure. RESULTS: The 23 patients whose data we analyzed had an average age of 77.9 ± 8.3 years. Most of them had left ventricular systolic dysfunction with an average ejection fraction of 34.1 ± 3.9%. The time between the start of symptoms and the first measurement was 6.7 ± 2.2 hours, while the time until the repeated determination was 6.5 ± 2.2 hours after the first measurement. The median value of the NT-proBNP levels in the 6 hours control showed an increase from 5064 pg/mL to 8847 pg/mL (p<0.0005), which amounts to a 75 percent increase - mean hs-troponin T showed an increase from 46 ± 25 ng/L to 78 ± 51 ng/L (p<0.002). CONCLUSIONS: A significant increase in NT-proBNP levels is to be expected in early repeated measurement after hospital admission. This fact could have diagnostic and prognostic consequences if validated in a larger patient population. Orv Hetil. 2018; 159(25): 1009-1012.

[The significance of ECG recorded at hospitalization in determining the prognosis of patients treated with myocardial infarction]. / A kórházi felvétel idején rögzített EKG jelentosége a szívinfarktus miatt kezelt betegek prognózisának meghatározásában.

INTRODUCTION AND AIM: By using the database of the National Registry of Myocardial Infarction, the authors examine the prognosis of patients treated with acute myocardial infarction, in case of whom there was new or presumably new left bundle branch block (nLBBB) on the ECG recorded at hospitalization. METHOD: We recorded the details of 18 091 patients treated with acute myocardial infarction (AMI) between 1 January 2014 and 30 June 2015 in the National Registry of Myocardial Infarction. In case of 8334 patients, the clinical diagnosis was ST-elevation myocardial infarction (STEMI), whereas in 9757 cases it was non-ST elevation myocardial infarction (NSTEMI). In the STEMI population we examined the clinical characteristics and prognosis of patients with ST-elevation (n = 7937) and nLBBB (n = 397). We used the proportional hazards regression model (Cox-regression) to examine mortality. RESULTS: In the AMI patient population, we found LBBB in 1274 cases (7%). In case of STEMI clinical diagnosis, the patients belonging to the nLBBB subpopulation (n = 397) were older, and the proportion of men and the occurrence of co-morbidities was higher than in case of those who had ST-elevation on their ECG recorded at hospitalization. The mortality rate of the LBBB population was higher than that of the ST-elevation patient population in both the 30-day (25.4% versus 12.4%) and the 1-year period (47.3 versus 19.9%). Percutaneous coronary intervention (PCI) had significantly lower mortality in both populations. In the course of a multifactorial analysis we verified the independent prognostic significance of LBBB: the hazard ratio compared to ST-elevation was 1.33 (95% confidence interval: 1.10-1.62), checked for gender, age, occurrence of PCI, systolic blood pressure, cardiac frequency, serum creatinine difference, and the details of five anamneses/co-morbidities. CONCLUSION: The admission ECG has prognostic significance. Patients with LBBB have poorer prognosis compared to patients with ST-elevation on admission ECG. Orv Hetil. 2018; 159(17): 677-681.