Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Multinational Trial.

BACKGROUND AND OBJECTIVES: In the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG Outcome), empagliflozin, in addition to standard of care, significantly reduced risk of cardiovascular death by 38%, hospitalization for heart failure by 35%, and incident or worsening nephropathy by 39% compared with placebo in patients with type 2 diabetes and established cardiovascular disease. Using EMPA-REG Outcome data, we assessed whether the Kidney Disease Improving Global Outcomes (KDIGO) CKD classification had an influence on the treatment effect of empagliflozin. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with type 2 diabetes, established atherosclerotic cardiovascular disease, and eGFR≥30 ml/min per 1.73 m2 at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. Post hoc, we analyzed cardiovascular and kidney outcomes, and safety, using the two-dimensional KDIGO classification framework. RESULTS: Of 6952 patients with baseline eGFR and urinary albumin-creatinine ratio values, 47%, 29%, 15%, and 8% were classified into low, moderately increased, high, and very high KDIGO risk categories, respectively. Empagliflozin showed consistent risk reductions across KDIGO categories for cardiovascular outcomes (P values for treatment by subgroup interactions ranged from 0.26 to 0.85) and kidney outcomes (P values for treatment by subgroup interactions ranged from 0.16 to 0.60). In all KDIGO risk categories, placebo and empagliflozin had similar adverse event rates, the notable exception being genital infection events, which were more common with empagliflozin for each category. CONCLUSIONS: The observed effects of empagliflozin versus placebo on cardiovascular and kidney outcomes were consistent across the KDIGO risk categories, indicating that the effect of treatment benefit of empagliflozin was unaffected by baseline CKD status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: EMPA-REG OUTCOME, NCT01131676.

Hemiblocks revisited.

The trifascicular nature of the intraventricular conduction system and the concept of trifascicular block and hemiblock were described by Rosenbaum and his coworkers in 1968. Since then, anatomic, pathological, electrophysiological, and clinical studies have confirmed the original description and scarce advances have been developed on the subject. In the present study, we attempt to review and redefine reliable criteria for the electrocardiographic and vectorcardiographic diagnosis of left anterior and posterior hemiblock. One of the most important problems related to hemiblocks is that they may simulate or conceal the electrocardiographic signs of myocardial infarction or myocardial ischemia and may mask or simulate ventricular hypertrophy. Illustrative examples of these associations are shown to help the interpretation of electrocardiograms. The incidence and prevalence of the hemiblocks is presented based on studies performed in hospital patients and general populations. One of the most common causes of hemiblocks is coronary artery disease, and there is a particularly frequent association between anteroseptal myocardial infarction and left anterior hemiblock. The second most important cause is arterial hypertension, followed by cardiomyopathies and Lev and Lenègre diseases. The hemiblocks may also occur in aortic heart disease and congenital cardiopathies. Left anterior hemiblock is more common in men and increases in frequency with advancing age. Evidence is presented regarding the relationship of spontaneous closure of ventricular septal defects, which may explain the finding of this and other conduction defects in young populations. Isolated left anterior hemiblock is a relatively frequent finding in subjects devoid of evidence of structural heart disease. Conversely, isolated left posterior hemiblock is a very rare finding; its prognostic significance is unknown and is commonly associated with right bundle-branch block. The most remarkable feature of this association is that the prognosis is much more serious with a great propensity to develop complete atrioventricular block and Adams-Stoke seizures.

Heart block and hyperthyroidism. Report of two cases.

In two patients with hyperthyroidism who had no signs of heart disease, first-degree heart block with tall and large P waves occurred. In one patient, a left bundle-branch block and transient complete heart block with Stokes-Adams episodes also occurred, although there was no verifiable evidence of acute inflammatory disease.

Arrhythmias and Stokes-Adams attacks in acute rheumatic fever.

In spite of general complacency about first-degree heart block in acute rheumatic fever, abnormal conduction with dysrhythmias, occasional complete heart block, and, rarely, Stokes-Adams attacks are important early signs of acute rheumatic fever and may precede other signs. Every person with episodic fainting is entitled to an ECG, and frequent ECGs are imperative in any case of rheumatic fever with signs of arrhythmias. Changing atrioventricular block necessitates continuous monitoring for dysrhythmias. A 13-year-old boy who appeared with Stokes-Adams attacks secondary to acute rheumatic fever was successfully treated by temporary pacing.

Adams-Stokes seizures due to ventricular tachydysrhythmias in patients with heart block: prevalence and problems of management.

One hundred and twelve patients with heart block and chronic tendency to syncope were ECG-monitored during syncope. Ventricular tachycardia and/or fibrillation (VT-VF) was observed as the cause of syncope in 11 patients: in 6 of 20 patients with chronic third degree A-V block, in 3 of 65 with paroxysmal A-V block and in 2 of 27 with S-A block. The R-R interval preceding the escape beat which initiated VT-VF varied between 1.2 and 2.2 seconds. The cerebral attacks were amenable to long-term pacemaker treatment. However, relapses of VT-VF were observed during pacing with a low rate of 55 per minute and during short interruptions in pacing, as produced by intermittent pacemaker failure or threshold determination. In one patient, supplementary treatment with a beta-blocking agent had to be given to suppress exercise-induced attacks of VT-VF after pacemaker implantation.

Complete heart block mimicking seizure disorder.

Two patients are described who presented with seizures. Electrocardiogram revealed complete heart block with ventricular asystole lasting four to 10 seconds in each case. These Stokes-Adams episodes were controlled with temporary transvenous pacing. Although there was full clinical recovery in each case, both patients continue to have right bundle branch block (RBBB) and left anterior hemiblock (LAH) 1-1/2 years after their initial presentation.

[Infranodal chronic auriculo-ventricular block in subjects under 50 years of age]. / Les blocs auriculo-ventriculaires chroniques infranodaux des sujets de moins de 50 ans.

The aetiology and evolution of chronic infranodal atrioventricular block (AVB) of young patients are not well known: are they the first sign of subclinical myocardial disease which can only be diagnosed by long term follow-up or do they represent isolated degenerative disease of the conduction tissue (Lenegre's disease)? Eighteen patients (15 men, 3 women) aged 25 to 49 years (average 41.5 years) were followed up for periods of 2 to 20 years (average 7.33 years) after pacemaker implantation for syncopal AVB. Follow-up was focused on the evolution of the conduction defects and the cardiovascular status. The patients were divided into two groups at the initial assessment: Group I: 15 patients with documented AVB; Group II: 3 patients in whom all basal recordings showed sinus rhythm (SR). Apart from one patient with an early non-ischaemic dilated cardiomyopathy, there was no previous cardiovascular disease. There was no history of ischaemic heart disease, drug effects, infection or inflammation in favour of an acute AVB. Three patients had permanent AVB, either 2nd degree with bundle branch block (N = 2) or 3rd degree block (N = 1). The other 15 patients were in sinus rhythm with bundle branch block: left bundle branch block (LBBB) in 5 cases, right bundle branch block (RBBB) in 3 cases; RBBB with left anterior hemiblock in 5 cases, RBBB and left posterior hemiblock in 2 cases. Paroxysmal AVB was recorded in 12 of these 15 patients on at least one occasion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute nonspecific carditis in adolescents presenting with Stokes-Adams attacks.

Three patients, aged between 12 and 17 years presented with Stokes-Adams attacks as a result of atrioventricular block, atrioventricular silence and ventricular arrhythmias, complicating acute myocarditis. All the patients required temporary pacing for a few days. One patient required hemodialysis for anuria. All the patients made complete recovery.

[Recurrent episodes of Morgagni-Adams-Stokes syndrome due to degeneration of atrio-ventricular tachycardias into atrial fibrillation in a patient with Wolf-Parkinson-White syndrome]. / Nawracajacy zespól MAS w nastepstwie przeksztalcania sie czestoskurczu przedsionkowo-komorowego w migotanie przedsionków u chorej z zespolem WPW.

We present clinical problems and the therapy of a 52 year old patient with Wolf-Parkinson-White syndrome and numerous episodes of Morgagni-Adams-Stokes syndrome. In that patient atrio-ventricular tachycardia caused atrial fibrillation. Short refractory period of the accessory pathway and the ventricular muscle allowed for extremely fast ventricular rate with haemodynamic collapse and syncope. Long-term treatment with propafenone or amiodarone did not prevent the arrhythmias. Electrophysiological study pre- and intraoperation including the epicardial mapping were performed several weeks after discontinuation of therapy with amiodarone. The studies revealed left free wall accessory pathway. Dr. A. Biederman and al. performed dissection of the accessory pathway. There were no evidence of conduction through the accessory pathway during the post operation electrophysiologic study. The patient has neither reentrant tachycardias nor atrial fibrillation episodes.

[Adams-Stokes syncope disclosing a crisis of rheumatic fever. Apropos of a case]. / Syncope d'Adams Stokes révélant une crise de rhumatisme articulaire aigu. A propos d'un cas.

A high degree atrioventricular block (AVB) is an exceptional finding during an acute episode of rheumatic fever (RF). The authors report a case of complete syncopal AVB requiring a temporary pacemaker, representing the first episode of RF.

[Assessment of third-degree congenital atrioventricular block by ergometric tests]. / Avaliação do bloqueio atrioventricular do 3 degrees. grau congênito pelo teste ergométrico.

PURPOSE: To analyse the use of the exercise testing as the method of initial evaluation, following a prognostic indicative of patients with congenital complete heart block. METHODS: Five patients were analysed (3 men and 2 woman) with ages between 7 and 34 years (mean = 22.8). The patients were submitted to a treadmill exercise testing using the Bruce protocol 1 and symptom limited. RESULTS: In all patients the atrial frequency increased from a median of 74.40 bpm in the basal to 155.20 bpm in the maximum effort; the atrial chronotropism was a little below that calculated based on the age of the patients. The median of the ventricular frequency in the maximum effort was 94.80 bpm, very different from that foreseen and showing a deficit of ventricular chronotropism. The median consumption of oxygen was 35.68ml0(2)/Kg/min. In one patients (20%) there was not any change in the ventricular frequency with the effort, in 3 (60%) complex ventricular arrhythmia arise during the effort and in one (20%) a definitive ventricular pacemaker was implanted. CONCLUSIONS: The exercise testing is a simple method of initial evaluation, providing information as chronotropism, functional capacity and the presence of arrhythmias, that can be very useful in the evaluation of prognostic. The presence of complex ventricular arrhythmias during the exercise is indicative of a more regular follow-up.

[Malignant lymphoma with Adams-Stokes syndrome as the first manifestation].

A case of malignant lymphoma with Adams-Stokes attack which was the first manifestation was reported. A 56-year-old female admitted our institute because of unconsciousness attack. After implantation of pacemaker she had high fever and abdominal mass. Ga scintigraphy revealed many accumulation on the hepatic hilus and the heart. Abdominal Computed Tomography and echography revealed abnormal mass in the hepatic hilus. The biopsy of this abnormal mass was performed. The histological examination of this specimen showed diffuse middle sized type malignant lymphoma.

[Integrated traditional and Western medicine treatment of severe viral myocarditis].

33 patients divided into 2 groups for treatment. Group A (18 cases) early use of adrenal cortico-steroid treatment in combination with traditional Chinese medicine; group B (15 cases): early use of adrenal cortico-steroid treatment is combination with interferon, then compared the therapeutic effects of these 2 groups. The results showed that, in these 2 groups, the sinus-atrial block, atrial ventricular block, ventricular tachycardia, acute pump failure as well as the EKG changes were relieved and improved to the same degree. In group A, after therapy, the parameters of OKT3 (%) was elevated from 51 +/- 15.22 to 55.23 +/- 8.53; OKT4(%) was elevated from 30.06 +/- 11.47 to 47.32 +/- 10.87; ratio of OKT4/OKT8 was elevated from 1.11 to 1.53; all of their P values were < 0.01. NK cell activity was elevated from 8.36 +/- 3.75 to 13.08 +/- 5.77, P value < 0.05. In group B, the parameters of OKT3 (%) was elevated from 50.91 +/- 8.12 to 56.75 +/- 8.29; OKT4 (%) was elevated from 32. 55 +/- 6.78 to 45.13 +/- 10.85; ratio of OKT4/OKT8 was elevated from 1.00 +/- 0.21 to 1.37 +/- 0.16; P value < 0.05, < 0.05 and < 0.01 respectively. NK cell activity (%) was elevated from 8.20 +/- 3.08 to 14. 0.3 +/- 4.89, P value also < 0.01. Hence, not only in group A but also in group B, after therapy, the parameters of OKT3,4,8, OKT4/OKT8 and NK cell activity (%) were all improved. But there was no significant statistical difference between group A and B.(ABSTRACT TRUNCATED AT 250 WORDS)

[Complete atrioventricular block in Becker-type muscular dystrophy]. / Calkowity blok przedsionkowo-komorowy w przebiegu dystrofii miesniowej typu Beckera.

A case is described of Becker type muscular dystrophy in a man aged 52 years, in whom complete atrioventricular block was found with Morgagni-Adams-Stokes attacks. The pathogenesis of the syndrome and the necessity of implantation of a pacemaker are discussed.

[Physician's approach in treating myocardial infarct complicated by a transverse heart block]. / Taktika vracha pri lechenii bol'nykh infarktom miokarda, oslozhnivshimsia poperechnoi blokadoi serdtsa.

On the basis of the results of observation over 253 patients in whom the acute period of myocardial infarction was complicated by atrioventricular block, the author recommends the therapeutic tactics in this group of patients. It is shown that electrical stimulation is the most effective method of treatment in complete atrioventricular block. Analysis of the natural course of atrioventricular block in myocardial infarction shows that the artificial pacemaker should be implanted not earlier than 4 weeks after the development of the block, if the block does not disappear by that time. Data on the condition of circulation obtained by means of the routine physical methods of examination are the most valuable criteria in the choice of the ortimum parameters of electrical stimulation of the heart.

[The natural course of a complete atrioventricular block]. / Estestvennoe techenie polnoi atrioventrikuliarnoi blokady.

The natural disease course is analyzed in 311 patients with atrioventricular blockade admitted for surgical treatment to the Leningrad Center of Arrhythmia Surgery and Cardiac Pacing. It has been discovered that, as a rule, Morgagni-Adams-Stokes (MAS) attacks do not occur for over 2-3 years after their onset, which determines to a considerable measure the patients: life expectancy. The authors hold that the very first Mas attack which may occur in a patient with atrioventricular blockade is an absolute indication for implantation of a permanent cardiac pacemaker. If the permanent cardiac pacemaker was established, 1-, 3-, 5-, 7- and 8-year survival rates were, respectively, 91.1, 85.8, 77.3, 63.2, and 60.8%.