Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Should We Be Using Upstream Beta-Blocker Therapy for Acute Myocardial Infarction?

PURPOSE OF REVIEW: Controversy exists whether beta-blockers should be given before primary percutaneous coronary intervention (PCI) or to defer their administration for up to 24 hours. RECENT FINDINGS: Animal studies, most of them conducted in the 1970s and 1980s, showed evidence that early beta-blocker administration may reduce infarct size. Subsequent human studies had mixed results on infarct size and survival. More specifically, in the current primary PCI era, only four studies evaluated the impact of early intravenous beta-blocker administration after acute myocardial infarction, only two of them before PCI. All studies agree that in hemodynamically stable patients, early intravenous beta-blocker administration is safe and protected against malignant arrhythmias. Nevertheless, results on infarct size and mortality are equivocal. Considering the heterogeneity of currently available data, further studies are still needed to assess the benefit of early injection of metoprolol in STEMI patients in a large double-blinded and randomized design versus placebo.

The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug-drug interaction (DDI): co-medication of metoprolol and paroxetine or fluoxetine in the elderly.

PURPOSE: Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies. METHOD: Dispensing data were collected from the University of Groningen pharmacy database (IADB.nl, 1999-2014) for elderly patients (≥60 years) starting beta-blockers and/or antidepressants. Based on the two main DDI alert systems (G-Standard and Pharmabase), incidences were divided between signalled (metoprolol-fluoxetine/paroxetine) and not-signalled (metoprolol-alternative antidepressants and alternative beta-blockers-paroxetine/fluoxetine) combinations. Incident users were defined as patients starting at least one signalled or a non-signalled combination. G-Standard signalled throughout the study period, whereas Pharmabase stopped after 2005. RESULTS: A total of 1763 patients had 2039 metoprolol-paroxetine/fluoxetine co-prescriptions, despite DDI alert systems, and about 57.3% were signalled. The number of metoprolol-alternative antidepressant combinations (incidences = 3150) was higher than alternative beta-blocker-paroxetine/fluoxetine combinations (incidences = 1872). Metoprolol users are more likely to be co-medicated with an alternative antidepressant (incidences = 2320) than paroxetine/fluoxetine users (incidences = 1232) are. The number of paroxetine/fluoxetine users co-prescribed with alternative beta-blockers was comparable to those co-medicated with metoprolol (about 50%). Less than 5% of patients received a substitute therapy after using metoprolol-paroxetine/fluoxetine. Most of the metoprolol users (90%) received a low dose (mean DDD = 0.47) regardless whether they were prescribed paroxetine/fluoxetine. CONCLUSION: Despite the signalling software, metoprolol-paroxetine/fluoxetine combinations are still observed in the elderly population. The clinical impact of these interactions needs further investigation. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial.

STUDY OBJECTIVE: We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. METHODS: This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. RESULTS: From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6). CONCLUSION: Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.

[Hypertrophic cardiomyopathy with midventricular obstruction of the left ventricle (MVO)--case report]. / Kardiomiopatia przerostowa ze sródkomorowym zawezaniem lewej komory (MVO)--opis przypadku.

A 76-year old woman with a history of stage 3 arterial hypertension, paroxysmal atrial fibrillation, hypercholesterolemia and type 2 diabetes mellitus. Ventricular tachycardia was the first clinical manifestation of the disease. Echocardiography revealed hypertrophic cardiomyopathy with a high intraventricular gradient of 47 mmHg and midventricular obstruction at the level of the papillary muscles (the lumen of the left ventricle was 1-2 mm during systole). No ventricular aneurysm was found but the ventricle was elongated and dilated in the periapical part where systolic function was decreased but synchronized in time. Coronary angiograms showed no narrowing of coronary arteries. A single-chamber cardioverter-defibrillator (ICD, implantable cardioverter-defibrillator) was implanted to prevent sudden cardiac death. Modified-release metoprolol and amiodarone were administered in antiarrhythmic therapy. This case represents a rare kind of hypertrophic cardiomyopathy in an elderly woman which is characterized by midventricular obstruction.

[Efficacy and safety of bisoprololal in hypertensive patients with cardiovascular disease and chronic obstructive pulmonary disease].

Efficacy and safety of bisoprolol in hypertensive patients with cardiovascular disease and chronic obstructive pulmonary disease. A comparative study on the efficacy and safety of bisoprolol and sustained release metoprolol succinate in patients with arterial hypertension (AH), cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) was conducted. High antihypertensive efficacy and good tolerability of bisoprolol and metoprolol succinate sustained release was shown in hypertensive patients with CVD and COPD. Bisoprolol versus metoprolol succinate sustained release was more effective in reducing the number of PVCs in hypertensive patients with CVD and COPD. After 12 weeks of therapy of bisoprolol there was a trend to reduce the number of patients with concentric left ventricular hypertrophy by 16.6 % (from 83.3% at baseline vs 66.7% after 12 weeks of treatment, p < 0.1). Despite the fact that the identified changes in respiratory function (ERF) in both groups did not reach certainty bisoprolol versus metoprolol succinate sustained-release was a lesser extent influenced the performance of ERF and more - to reduce dyspnea to the evaluation scales Borg and mMRC (delta% = -7.1 in fixed vs delta% = -3.8 in control groups and delta% = -5.6 vs delta% = 0 respectively) in patients with AH, CVD and COPD.

Napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura: a randomized controlled trial. / æž•é¡¹éƒ¨åŸ‹çº¿æ³•è”åˆé ’çŸ³é ¸ç¾Žæ‰˜æ´›å°”ç‰‡é¢„é˜²æ€§æ²»ç–—æ— å ˆå †åå¤´ç—›ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the efficacy of napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura, and to compare its efficacy with simple napex acupoint thread-embedding and simple metoprolol tartrate tablet. METHODS: A total of 105 patients with migraine without aura were randomized into a combination group (35 cases, 5 cases dropped out), a thread-embedding group (35 cases, 4 cases dropped out) and a western medication group (35 cases, 2 cases dropped out). In the thread-embedding group, napex acupoint thread-embedding was applied at bilateral Fengchi (GB 20) and points of 1.5 cun nearby to the lower edge of spinous process of cervical 2. In the western medication group, metoprolol tartrate tablet was given orally, 12.5 mg a time, twice a day. In the combination group, napex acupoint thread-embedding combined with oral metoprolol tartrate tablet was delivered. The treatment of 8 weeks was required in the 3 groups. The days of headache attacks, frequency of headache attacks, headache severity (visual analogue scale [VAS] score) and the migraine specific quality of life questionnaire version 2.1 (MSQ) score were observed during baseline period (4 weeks before treatment to before treatment), observation period (1-4 weeks and 5-8 weeks in treatment) and follow-up period (1-4 weeks after treatment completion) respectively, the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% were calculated, and the safety was evaluated in the 3 groups. RESULTS: During the observation period and the follow-up period, the days of headache attacks, frequency of headache attacks and headache VAS scores in the 3 groups were reduced compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the days of headache attacks and the frequency of headache attacks in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05); during the observation period (1-4 weeks in treatment), the headache VAS scores in the combination group and the thread-embedding group were lower than that in the western medication group (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the headache VAS scores in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were increased compared with those of the baseline period (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the role prevention scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05); during the follow-up period, the emotion function scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were higher than those in the thread-embedding group and the western medication group (P<0.05). There was no statistical difference in the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% among the 3 groups (P>0.05), and there were no serious adverse reactions in the 3 groups. CONCLUSIONS: Napex acupoint thread-embedding combined with metoprolol tartrate tablet, simple napex acupoint thread-embedding and simple metoprolol tartrate tablet all can reduce the days of headache attacks and the frequency of headache attacks, relieve headache severity and improve the quality of life in patients with migraine without aura. Napex acupoint thread-embedding combined with metoprolol tartrate tablet has a better effect.

Which should you choose for post operative atrial fibrillation, carvedilol or metoprolol? A systemic review and meta-analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. In comparing metoprolol succinate with carvedilol, the later has sparked interest in its usage as an important medication for POAF prevention. METHODS: We considered randomized controlled studies (RCTs) and retrospective studies that evaluated the efficacy of carvedilol versus metoprolol for the prevention of POAF. After literature search, data extraction, and quality evaluation, pooled data were analyzed using either the fixed-effect or random-effect model using Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes. RESULTS: In meta-analysis 5 RCTs and 2 retrospective studies with a total of 1000 patients were included. The overall effect did not favor the carvedilol over metoprolol groups in terms of mortality rate [risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] or incidence of bradycardia [risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001]. CONCLUSION: In patients undergoing cardiac surgery, carvedilol may minimize the occurrence of POAF more effectively than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, a large-scale, well-designed randomized controlled trials are required.

Metoprolol succinate vs. ivabradine in the treatment of inappropriate sinus tachycardia in patients unresponsive to previous pharmacological therapy.

AIMS: Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or disproportional increasing HR during exercise. The treatment of IST symptoms using beta-blockers or calcium channel-blockers is often non-effective or not well tolerated. Ivabradine is a new agent inhibiting sinus node I(f) current, resulting in a decrease of HR without haemodynamic compromise. METHODS AND RESULTS: We enrolled 20 patients (36 ± 10 years; 14 women) affected by IST and resistant to previous administered therapy by using beta-blockers or verapamil. After 4 weeks of treatment with metoprolol succinate (up to 190 mg once a day) the therapy was switched to ivabradine up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed after 1 and 2 months following start of the study. We observed a significant reduction of resting HR both for metoprolol and for ivabradine compared with baseline (92.8 vs. 90.2 vs. 114.3 b.p.m.; P< 0.001). During daily activity there was an even larger decrease of HR on ivabradine (mean daytime HR 94.6 vs. 87.1 vs. 107.3 b.p.m.; P< 0.001). Ivabradine was very well tolerated whereas in 10 patients on metoprolol we observed hypotension or bradycardia requiring dose reduction. Significantly lower incidence of IST-related symptoms were registered on ivabradine therapy than on metoprolol. Fourteen patients (70%) treated with I(f) blocker were free of IST-related complaints. CONCLUSIONS: Metoprolol and ivabradine exert a similar effect on resting HR in patients with IST. Ivabradine seems to be more effective to relieve symptoms during exercise or daily activity.

Transportability of two heart failure trials to a disease registry using individual patient data.

OBJECTIVES: Randomized controlled trials are the gold-standard for determining therapeutic efficacy, but are often unrepresentative of real-world settings. Statistical transportation methods (hereafter transportation) can partially account for these differences, improving trial applicability without breaking randomization. We transported treatment effects from two heart failure (HF) trials to a HF registry. STUDY DESIGN AND SETTING: Individual-patient-level data from two trials (Carvedilol or Metoprolol European Trial (COMET), comparing carvedilol and metoprolol, and digitalis investigation group trial (DIG), comparing digoxin and placebo) and a Scottish HF registry were obtained. The primary end point for both trials was all-cause mortality; composite outcomes were all-cause mortality or hospitalization for COMET and HF-related death or hospitalization for DIG. We performed transportation using regression-based and inverse odds of sampling weights (IOSW) approaches. RESULTS: Registry patients were older, had poorer renal function and received higher-doses of loop-diuretics than trial participants. For each trial, point estimates were similar for the original and IOSW (e.g., DIG composite outcome: OR 0.75 (0.69, 0.82) vs. 0.73 (0.64, 0.83)). Treatment effect estimates were also similar when examining high-risk (0.64 (0.46, 0.89)) and low-risk registry patients (0.73 (0.61, 0.86)). Similar results were obtained using regression-based transportation. CONCLUSION: Regression-based or IOSW approaches can be used to transport trial effect estimates to patients administrative/registry data, with only moderate reductions in precision.

Beta-blocker migraine prophylaxis affects the excitability of the visual cortex as revealed by transcranial magnetic stimulation.

The objective of this study is to assess effects of beta-blocker migraine prophylaxis on cortical excitability determined by transcranial magnetic stimulation (TMS). Phosphene and motor thresholds (PT, MT) were investigated in 29 patients with migraine, in 15 of them prior to and following preventive medication with metoprolol and in 14 patients without prophylaxis. Following prophylaxis headache frequency significantly decreased (p = 0.005) and mean PT were significantly increased (51.5 ± 7.5 vs. 63.6 ± 8.4%) compared to patients without preventive treatment (53.7 ± 5.3 vs. 52.3 ± 6.3%; p = 0.040). Mean MT did not significantly differ either between groups or due to treatment. In the group of all patients, a significant inverse correlation between headache frequency and the level of PT was found (R = -0.629; p < 0.01). There was, however, no significant correlation in the subgroups of patients. We conclude that (a) clinical efficacy of beta-blocker treatment in migraine could be (at least partly) linked to its ability to modulate the excitability of the visual cortex and (b) the PT determined by TMS appears suitable to assess the effects of prophylaxis on cortical excitability in the individual patient. This may be useful in clinical trials investigating migraine preventive drugs.

Torasemide-induced Vascular Purpura in the Course of Eosinophilic Granulomatosis with Polyangiitis.

Torasemide is a loop diuretic with a molecule that is chemically similar to the sulphonamides described as eosinophilic granulomatosis with polyangiitis (EGPA) triggering drugs. The presented case is probably the first description of torasemide-induced vascular purpura in the course of EGPA. Any diagnosis of vasculitis should be followed by an identification of drugs that may aggravate the disease. A 74-year-old patient was admitted to the Department of Dermatology with purpura-like skin lesions on the upper, and lower extremities, including the buttocks. The lesions had appeared around the ankles 7 days before admission to the hospital and then started to progress upwards. The patient complained on lower limb paresthesia and pain. Other comorbidities included bronchial asthma, chronic sinusitis, ischemic heart disease, mild aortic stenosis, arterial hypertension, and degenerative thoracic spine disease. The woman had previously undergone nasal polypectomy twice. She was on a constant regimen of oral rosuvastatin 5 mg per day, spironolactone 50 mg per day, metoprolol 150 mg per day, inhaled formoterol 12 µg per day, and ipratropium bromide 20 µg per day. Ten days prior to admission, she was commenced on torasemide at a dose of 50 mg per day prescribed by a general practitioner due to high blood pressure. Doppler ultrasound upon admission to the hospital excluded deep venal thrombosis. The laboratory tests revealed leukocytosis (17.1 thousand per mm3) with eosinophilia (38.6%), elevated plasma level of C-reactive protein (119 mg per L) and D-dimers (2657 ng per mm3). Indirect immunofluorescent test identified a low titer (1:80) of antinuclear antibodies, but elevated (1:160) antineutrophil cytoplasmic antibodies (ANCA) in the patient's serum. Immunoblot found them to be aimed against myeloperoxidase (pANCA). A chest X-ray showed increased vascular lung markings, while high-resolution computed tomography revealed peribronchial glass-ground opacities. Microscopic evaluation of skin biopsy taken from the lower limbs showed perivascular infiltrates consisting of eosinophils and neutrophils, fragments of neutrophil nuclei, and fibrinous necrosis of small vessels. Electromyography performed in the lower limbs because of their weakness highlighted a loss of response from both sural nerves, as well as slowed conduction velocity of the right tibial nerve and in both common peroneal nerves. Both clinical characteristics of skin lesions and histopathology suggested a diagnosis of EGPA, which was later confirmed by a consultant in rheumatology. The patient was commenced on prednisone at a dose of 0.5 mg per kg of body weight daily and mycophenolate mofetil at a daily dose of 2 g. The antihypertensive therapy was modified, and torasemide was replaced by spironolactone 25 mg per day. The treatment resulted in a gradual regression of skin lesions within a few weeks. The first report of EGPA dates back to 1951. Its authors were Jacob Churg and Lotte Strauss. They described a case series of 13 patients who had severe asthma, fever, peripheral blood eosinophilia, and granulomatous vasculitis in microscopic evaluation of the skin. Three histopathological criteria were then proposed, and Churg-Strauss syndrome was recognized when eosinophilic infiltrates in the tissues, necrotizing inflammation of small and medium vessels, and the presence of extravascular granulomas were observed together in a patient (1). Only 17.4% of patients met all three histopathological criteria, and the diagnosis of the disease was frequently delayed despite of its overt clinical picture (2). In 1984, Lanham et al. proposed new diagnostic criteria which included the presence of bronchial asthma, eosinophilia in a peripheral blood smear >1.5 thousand per mm3, and signs of vasculitis involving at least two organs other than the lungs (3). Lanham's criteria could also delay the recognition of the syndrome before involvement of internal organs, and the American College of Rheumatology therefore established classification criteria in 1990. These included the presence of bronchial asthma, migratory infiltrates in the lungs as assessed by radiographs, the presence of abnormalities in the paranasal sinuses (polyps, allergic rhinitis, chronic inflammation), mono- or polyneuropathy, peripheral blood eosinophilia (>10% of leukocytes must be eosinophils), and extravascular eosinophilic infiltrates in a histopathological examination. Patients who met 4 out of 6 criteria were classified as having Churg-Strauss syndrome (4). The term EGPA was recommended to define patients with Churg-Strauss syndrome in 2012 (5). EGPA is a condition with low incidence (0.11-2.66 cases per million) and morbidity. It usually occurs in the fifth decade of life (6,7), although 65 cases reports of EGPA in people under 18 years of age could be found in the PubMed and Ovid Medline Database at the end of 2020 (8). The etiopathogenesis of the disease has not been fully explained so far. Approximately 40-60% of patients are positive to pANCA (9), but the role of these antibodies in the pathogenesis of EGPA remains unclear. They are suspected to mediate binding of the Fc receptor to MPO exposed on the surface of neutrophils. Subsequently, this may active neutrophils and contribute to a damage of the vascular endothelium (9,10). Glomerulonephritis, neuropathy, and vasculitis are more common in patients with EGPA who have detectable pANCA when compared with seronegative patients. There are at least several drugs which potentially may EGPA. The strongest association with the occurrence of EGPA was found with the use of leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast), although they are commonly used in the treatment of asthma, which is paradoxically one of the complications of the syndrome (13). Although no relationship has been demonstrated so far between the occurrence of EGPA and the intake of drugs from the groups used by the presented patient, a clear time relationship can be observed between the commencement of torasemide and the onset of symptoms in our patient. To date, only three cases of leukocytoclastic vasculitis have been reported after the administration of torasemide. Both of them developed cutaneous symptoms of the disease within 24 hours of the administration of torasemide in patients with no previous history of drug hypersensitivity, but they disappeared quickly within 8-15 days after drug discontinuation (14,15). The chemical structure of torasemide is similar to the molecule of sulfonamides which were previously found to be a triggering factors for EGPA (12). This drug belongs to the group of loop diuretics classified as sulfonamide derivatives. A comparison of the chemical structure of torasemide and sulphanilamide molecules is presented in Figure 1. The clear time relationship between starting the administration of torasemide and the occurrence of purpura-like lesions suggests that it was an aggravating factor for EGPA in our patient. A coexistence of several disorders (asthma, nasal polyps, symptoms of peripheral neuropathy) in our patient suggest EGPA could have developed in her years before oral intake of torasemide. The sudden onset of skin symptoms shows torasemide to be possible inducing factor for the development of vascular purpura in patients suffering from EGPA but without previous cutaneous involvement.

[Ischemic heart disease in elderly patients of behavioral type A (psychosocial and clinic functional changes, possibilities for correction)].

833 patients aged 32 to 74 years who had coronary heart disease (CHD) were examined. Psychosocial and clinicofunctional features typical for elderly people of behavioral type A and with diagnosed CHD and ways for treatment optimization and disease prophylaxis are being under consideration. We studied the clinical efficiency and influence of Anaprilin, Metoprolol, Phenazepam, non-medical methods on psychoendocrine parameters in CHD elderly patients with behavioral type A. In addition to positive changes in the anginal syndrome sleep, decreases in hot temper, irritability, anxiety, phobic manifestations, hypochondrial trends, and neurotic asthenization, increased working and social orientation were improved. During Anaprilin, Metoprolol, Phenazepam therapy, cardialgias reduced or disappered, the incidence of arrhythmia decreased. There was a reduction in the personality profile in the neurotic triad and psychoasthenia scales, the reactive anxiety diminished significantly, and levels of aldosterone, cortisol, triiodothyronine, and thyroxine in the blood decreased. Thus, supplementation of Anapriline, Metoprolol, Phenazepam to the combined therapy for patients with CHD of behavioral type A positively effected to the clinical course of the disease. Configuration of the personality profile was leveled in patients with CHD of coronary type, signs of behavioral type A decreased.

Metoprolol for prophylaxis of postoperative atrial fibrillation in cardiac surgery patients: systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after open heart surgery. This systematic review and meta-analysis aimed to investigate metoprolol compared with other treatments for prophylaxis against POAF. METHODS: We searched CENTRAL, MEDLINE, EMBASE and trial registries for randomised controlled trials that evaluated metoprolol for preventing the occurrence of POAF after surgery against other treatments or placebo. Random-effects model was used for estimating the risk ratios (RRs) and mean differences with 95% CIs. RESULTS: Nine trials involving 1570 patients showed metoprolol reduced POAF compared with placebo (416 patients; RR 0.46, 95% CI 0.33 to 0.66; I²=21%; risk difference (RD) -0.19, 95% CI -0.28 to -0.10). However, metoprolol increased the risk of POAF compared with carvedilol (159 patients; RR 1.59, 95% CI 1.20 to 2.12; I²=4%; RD 0.13, 95% CI 0.06 to 0.20). There was no difference when compared with sotalol or amiodarone. The occurrence of cardiovascular conditions after drugs administration or death between the groups was not different. The overall quality of evidence was moderate to high. Subgroup analysis and funnel plot were not performed. CONCLUSIONS: Metoprolol is effective in preventing POAF compared with placebo and showed no difference with class III antiarrhythmic drugs. Death and thromboembolism are associated with open heart surgery, but not significant in relation to the use of metoprolol. PROSPERO REGISTRATION NUMBER: CRD42019131585.

[Thrombosed giant proximal pulmonary artery aneurysm]. / Trombozlu dev proksimal pulmoner arter anevrizmasi.

We present a 36-year-old male patient with a previous diagnosis (22 years) of Eisenmenger's syndrome, who had a giant proximal pulmonary artery aneurysm complicated by massive thrombus formation. The patient experienced paroxysmal atrial fibrillation attacks for the past month. His functional capacity was New York Heart Association class III. Chest radiography showed aneurysmal dilatation in the left pulmonary artery. The patient was assessed by transthoracic echocardiography and multislice computed tomography. There was mild narrowing in the thick and calcified pulmonary valve (peak systolic gradient 35 mmHg) and moderate regurgitation. The mean pulmonary artery pressure was estimated as 50 mmHg. The diameters of the main, left, and right pulmonary arteries were 6.5 cm, 10 cm, and 3.7 cm, respectively. There was a massive thrombus in the aneurysmatic left pulmonary artery. The patient was referred to the cardiovascular surgery department for pulmonary artery reconstruction and cardiopulmonary transplantation. In addition, medical treatment was instituted with warfarin for thrombus and paroxysmal atrial fibrillation, metoprolol for atrial fibrillation, and bosentan for pulmonary hypertension. The patient's functional capacity showed improvement after the first month of medical treatment and no complications were seen within a year follow-up.

Hydrochlorothizide-induced acute generalised exanthematous pustulosis presenting with bilateral periorbital impetigo.

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterised by the appearance of erythematous plaques and papules with overlying non-follicular pinpoint pustules. Drugs are the cause of AGEP in approximately 90% of cases. The most common causes include anti-infective agents (aminopenicillins, quinolones, antibacterial sulfonamides and terbinafine), antimalarials and diltiazem. To the best of our knowledge, to date there has only been one report of hydrochlorothiazide-induced AGEP. There has never been a case report of losartan-induced AGEP. Here, we present a case of AGEP that is the second case purportedly caused by hydrochlorothiazide.

[Termination of atrio-ventricular reentrant tachycardia in a pregnant woman using transoesophageal atrial pacing and pharmacotherapy]. / Czestoskurcz wezlowy nawrotny u ciezarnej wyzwalany ektopia komorowa - opis postepowania stymulacyjno-farmakologicznego przywracajacego rytm zatokowy.

We describe a case of a 19-year-old pregnant woman with paroxysmal atrio-ventricular reentrant tachycardia (AVNRT). Transoesophageal atrial pacing (TAP) successfully terminated the arrhythmia, however, AVNRT restarted after 20 min and was initiated by ventricular ectopy. Intravenous metoprolol effectively suppressed ventricular ectopy and AVNRT did not recur. A modification of the ESC algorithm, with the inclusion of pacing techniques to terminate AVNRT, is proposed.

Intravenous administration of metoprolol is more effective than oral administration in the prevention of atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery, with an incidence of 20% to 40%. AF is associated with postoperative complications, including increased risk of stroke and need of additional treatment, as well as prolonged hospital stay and increased costs. It has been shown that prophylactic oral administration of beta-blocker therapy reduces the incidence of postoperative AF after cardiac surgery. However, it is possible that absorption of drugs is impaired after cardiopulmonary perfusion associated with cardiac surgery. The purpose of this prospective, controlled, randomized trial was to study compare intravenous and per oral metoprolol administration in the prevention of AF after cardiac surgery. METHODS AND RESULTS: 240 consecutive patients who were scheduled to undergo their first on-pump coronary artery bypass graft (CABG), aortic valve replacement, or combined aortic valve replacement and CABG were randomized to receive 48-hour infusion of metoprolol or oral metoprolol starting on the first postoperative morning. Patients were excluded if they had contraindications for beta-blocker or had to stay >1 day in the intensive care unit. Dosage of metoprolol was adjusted according to heart rate. The dosage was 1 to 3 mg/h in the intravenous group and from 25 mg twice per day to 50 mg 3 times per day in the oral group. The incidence of postoperative AF was significantly lower in the intravenous group than in the oral group (16.8% versus 28.1%, P=0.036). No serious adverse effects were associated with intravenous metoprolol therapy. CONCLUSIONS: Our study suggests that intravenous metoprolol is well-tolerated and more effective than oral metoprolol in the prevention of AF after cardiac surgery.

Does beta-blocker treatment influence central sleep apnoea?

UNLABELLED: Chronic severe heart failure is frequently associated with disturbances in the central control of breathing. During wakefulness, central breathing disorders could be ameliorated with beta-blocker treatment, but nothing is known about the effects of beta-blockers on the control of breathing during sleep. This study intends to determinate the prevalence and severity of nocturnal apnoeas and hypopnoeas in heart failure patients treated with or without metoprolol or carvedilol. Fifty consecutive patients with dilated cardiomyopathy in NYHA class II-IV with a left ventricular ejection fraction (LVEF) of 35% or below were studied with full polysomnography over one night. The mean Apnoea-Hypopnoea Index of beta-blocker free patients was 19.8+/-14.2 versus 7.4+/-8.5 (p<0.05) and 8.7+/-8.1 (p<0.05) in patients treated with metoprolol or carvedilol, respectively. The arousal index, sleep quality, and daytime sleepiness were improved in similar magnitude. CONCLUSION: Long-term treatment of patients with advanced chronic heart failure with sufficient doses of metoprolol or carvedilol is associated with a lower prevalence and severity of central sleep apnoea (CSA).