Effects of exercise training after acute coronary syndromes in octogenarians - prospective 12-month evaluation.

OBJECTIVE: Aim: To demonstrate the impact of individual exercise training on the course of the disease, exercise tolerance and quality of life (QoL) in patients over 75 years after acute coronary syndrome (ACS). PATIENTS AND METHODS: Materials and methods: Study included octogenarians after ACS randomly assigned into two groups: a training group (ExT) subjected to individualized physical training and a control group (CG) with standard recommendations for activity. Patients underwent exercise tolerance test (ETT), 6-minute walk test (6-MWT), NHP and QoL questionnaires evaluation, lab tests, ECG, echocardiographic examination at the beginning and after 2, 6 and 12 months. RESULTS: Results: Study included 51 patients, mean age 80 years, 50% men, all patients completed the study. Initial physical capacity was comparable in both groups. After 2-month training the average ETT exercise time increased by 12.5% (p=0.0004), the load increased by 13% (p=0.0005) and the 6-MWT results improved by 8.3% (p=0.0114). Among CG these changes were not significant. But 6 and 12 months after training cessation 6-MWT results returned to the initial values (p=0.069, p=0.062 respecitvely). Average ETT exercise time and average load decreased significantly after 12 months (p=0.0009, p=0.0006). Level of pain was significantly lower at the end of the training in ExT group (p=0.007), but it returned to initial 12 months later (p=0.48). QoL deteriorated significantly in the ExT group 12 months after training cessation (p=0.04). CONCLUSION: Conclusions: Cardiac rehabilitation in octogenarians after ACS was safe and improved physical performance in a short period of time. Cessation of training resulted in a loss of achieved effects and deterioration of the QoL.

Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.

BACKGROUND: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. METHODS: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. RESULTS: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. CONCLUSION: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

Pharmacological Cardioversion in Patients with Recent-Onset Atrial Fibrillation and Chronic Kidney Disease Subanalysis of the CANT II Study.

Pharmacological cardioversion (PCV) is commonly a primary option for termination of recent-onset atrial fibrillation (AF) in emergency departments (ED). This is a subanalysis of the CANT II study, evaluating the effectiveness and safety of antazoline in patients (n = 777) at three stages of chronic kidney disease (CKD): Group I > 60 mL/min (n = 531), Group II 45−59 mL/min (n = 149), and Group III < 45 mL/min (n = 97). Patients in Group III were older and with a higher prevalence of co-morbidities; however, we did not find statistically significant differences in the overall effectiveness of PCV in comparison with the other groups. In patients receiving amiodarone, the PCV success rate was similar in all the studied groups, but along with a renal function decline, it decreased in patients receiving antazoline (79.1 vs. 35%; p < 0.001), and it increased almost significantly in patients receiving propafenone (69.9 vs. 100%; p = 0.067). In patients in Group I, antazoline restored a sinus rhythm as effectively as propafenone and amiodarone; however, in patients in Group III, both antazoline and amiodarone became less effective in restoring a sinus rhythm than propafenone (p = 0.002 and p = 0.034, respectively). The rate of safety endpoint was the highest in patients in Group III (eGFR < 45 mL/min), and it was significantly higher than in patients in Groups I and II (p = 0.008 and p = 0.036, respectively). We did not observe antazoline-related adverse events in any of the studied groups of patients. This real-world registry analysis revealed a different influence of CKD on the effectiveness of individual drugs, and while propafenone and amiodarone maintained their AF termination efficacy, antazoline became significantly less effective in restoring sinus rhythm.

Outcomes With Intermediate Left Main Disease: Analysis From the ISCHEMIA Trial.

BACKGROUND: Patients with significant (≥50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. However, the impact of intermediate LMD (stenosis, 25%-49%) on outcomes is unclear. METHODS: Randomized ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%-49%) and without (<25%) intermediate LMD. The primary outcome was a composite of cardiovascular mortality, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The primary quality of life outcome was the Seattle Angina Questionnaire summary score. RESULTS: Among the 3699 participants who satisfied the inclusion criteria, 962 (26%) had intermediate LMD. Among invasive strategy participants with intermediate LMD on coronary computed tomography angiography, 49 (7.0%) had significant (≥50% stenosis) left main stenosis on invasive angiography. Patients with intermediate LMD had a higher risk of cardiovascular events in the unadjusted but not in the fully adjusted model compared with those without intermediate LMD. An invasive strategy increased procedural MI and decreased nonprocedural MI with no significant difference for other outcomes including the primary end point. There was no meaningful heterogeneity of treatment effect based on intermediate LMD status except for nonprocedural MI for which there was a greater absolute reduction with invasive management in the intermediate LMD group (-6.4% versus -2.0%; Pinteraction=0.049). The invasive strategy improved angina-related quality of life and the benefit was durable throughout follow-up without significant heterogeneity based on intermediate LMD status. CONCLUSIONS: In the ISCHEMIA trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate LMD status except for a greater absolute risk reduction in nonprocedural MI with invasive management in those with intermediate LMD. An invasive strategy increased procedural MI, reduced nonprocedural MI, and improved angina-related quality of life. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01471522.

Efficacy and safety of antazoline for cardioversion of atrial fibrillation: propensity score matching analysis of a multicenter registry (CANT II Study).

INTRODUCTION: Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of antazoline, a first­generation antihistamine, for cardioversion of recent­onset AF in the setting of an emergency department. PATIENTS AND METHODS: This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with new­onset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment. RESULTS: Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P <0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the post­PSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P <0.001), and the risk of adverse events was comparable (P = 0.2). CONCLUSIONS: Antazoline appears to be an efficacious agent for termination of AF in real­world setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.

Rapid pharmacological cardioversion of recent-onset atrial fibrillation using antazoline in elderly patients.

INTRODUCTION: There is insufficient evidence on the efficacy and safety of pharmacological cardioversion of recent­onset atrial fibrillation (AF) in elderly patients. Antazoline has been shown to be effective and safe in various patient populations. OBJECTIVES: We aimed to compare the clinical efficacy and safety of intravenous antazoline for pharmacological cardioversion of recent­onset AF between patients aged 75 years or older and those younger than 75 years. PATIENTS AND METHODS: This retrospective analysis was conducted using data derived from emergency room medical records of patients referred for pharmacological cardioversion due to symptomatic AF lasting less than 48 hours. The threshold for old age was set at 75 years. Conversion to sinus rhythm was considered the primary efficacy outcome. The primary safety outcome was defined as any adverse event requiring hospitalization. RESULTS: The study included 334 participants, of whom 110 patients were aged 75 years or older (study group) and 224 patients were younger than 75 years (controls). Successful cardioversion was achieved using lower mean (SD) antazoline doses in the study group than in controls: 151 (59) mg vs 168 (58) mg (P = 0.039). Study and control groups showed a similar efficacy and safety of antazoline (78.2% and 68.3%, respectively; odds ratio [OR], 1.66; 95% CI, 0.98-1.31; P = 0.06) as well as hospitalization rates (0.9% and 4.0%, respectively; OR, 0.22; 95% CI, 0.03-1.75; P = 0.17). CONCLUSIONS: Intravenous antazoline seems to be effective and safe for pharmacological cardioversion of recent­onset AF in elderly patients in the emergency setting.

Patterns of dyslipidemia in young patients with seronegative spondyloarthropathies without cardiovascular diseases.

OBJECTIVES: Patients with seronegative spondyloarthritis (SpA) - psoriatic arthritis (PsA) and ankylosing spondylitis (AS) - have a higher risk of cardiovascular morbidity and mortality. The aim of the present study was to evaluate the incidence and type of dyslipidemia, a potent atherosclerosis risk factor, in SpA patients. MATERIAL AND METHODS: It was a two-center, case-control study. Patients diagnosed with PsA and AS aged 23-60 years, with disease duration < 10 years, were enrolled. The inflammatory activity, serum levels of C-reactive protein (CRP) and lipid profile were evaluated in each patient. In patients > 40 years old, the 10-year risk of fatal cardiovascular disease (CVD), using Systematic Coronary Risk Evaluation (SCORE), was estimated. RESULTS: In total 79 patients with SpA were included in the study, with PsA diagnosed, n = 39 (mean age 45.1 ±9.6 years; 21, 53.9%, women), and with AS diagnosed, n = 40 (age 40.3 ±9.5; 12.3%, women), control group (CG): n = 88 (age 42.3 ±8.1; 42, 47.7% women). Based on the interview and laboratory tests, dyslipidemia was diagnosed in 19 (47.5%) patients with AS and in 28 (71.8%) patients with PsA. Most patients had hypercholesterolemia or mixed hyperlipidemia. Types of dyslipidemia were similar. In SpA patients (PsA and AS), the level of triglycerides (TG) and atherogenic index (AI) were significantly higher than in the CG, respectively TG in SpA: 116 (83-156) and in the CG: 91.2 (72.6-134.6) mg/dl, p = 0.0182; AI in SpA: 3.77 ±1.26 and in the CG: 2.58 ±1.27, p < 0.0001.The low-density cholesterol (LDL) level was significantly lower in SpA patients than in the CG, SpA: 109.1 ±29.4 vs. CG: 125.2 ±35.9 mg/dl, p = 0.0023. There was a strong negative correlation between CRP levels and HDL cholesterol levels in patients with PsA, rho = 0.42, p = 0.0132. Mean SCORE values were 2.33% in PsA patients and 2.38% in AS patients, which results in moderate 10-year risk of death from CVD. CONCLUSIONS: In young patients with spondyloarthropathies, inflammatory factors significantly influence dyslipidemia patterns, which result in higher TG and lower LDL cholesterol levels. In patients with PsA, dyslipidemia was diagnosed more often than in patients with AS.

Optimal medical therapy in patients with stable coronary artery disease in Poland: the ISCHEMIA trial experience.

Introduction: Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. Objectives: To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. Patients and methods: Among 5179 trial participants, 333 were randomized in Poland. The median follow-up was 3.2 years. OMT targets were: not smoking, high-intensity statin therapy, low-density lipoprotein cholesterol (LDL-C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and ß-blocker therapy if indicated. Results: Compared with 36 other countries, at randomization, patients in Poland were older (67 [62­75] y vs 65 [58­71] y); P <⁠0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [1­9] y vs 1 [0­3] y; P <⁠0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <⁠0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <⁠0.001 for both). The number of OMT goals attained increased from baseline to follow-up visits (5 [4­5] vs 6 [5­6]; P <⁠0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high-intensity statin therapy (27% vs 50%), LDL-C <⁠70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <⁠0.001 for all), whereas not-smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and ß-blocker therapy (94% vs 90%) remained high. Conclusions: With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL-C and blood pressure management.

Profile and treatment of chronic coronary syndromes in European Society of Cardiology member countries: The ESC EORP CICD-LT registry.

BACKGROUND: International guidelines recommend pharmacotherapy combinations for chronic coronary syndromes (CCSs) but medical management remains suboptimal. DESIGN: The CICD-LT registry is investigating short- and long-term outcomes and management in patients in European Society of Cardiology (ESC) member countries, in a longitudinal ESC EURObservational Research Programme aimed at improving CCS management. METHODS: Between 1 May 2015 and 31 July 2018, 9174 patients with previous ST-elevation myocardial infarction (STEMI), non-STEMI or coronary revascularisation, or other CCS, were recruited during a routine ambulatory visit or elective revascularisation procedure. Baseline clinical data were recorded and prescribed medications analysed at initial contact and discharge, and according to patient gender and age (<75 vs. ≥75 years). RESULTS: Poorly controlled cardiovascular risk factors, including current smoking (18.5%), obesity (33.9%), diabetes (25.8%), raised low-density lipoprotein cholesterol (73.3%) and persistent hypertension (24.7%), were common across all cohorts. At ambulatory visit or admission, the guidelines-recommended combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, aspirin, statin and any antiplatelet agent was prescribed to 57.8% of patients with STEMI/NSTEMI. Differences in prescribing rates, including for combination therapies, were observed based on age and gender and persisted after adjustment for demographic factors. CONCLUSIONS: Cardiovascular risk factors were common in contemporary CCS patients and secondary prevention prescribing was suboptimal. Patients aged ≥75 years and, to some extent, female patients were less likely to receive guidelines-recommended drug combinations than younger and male patients. One- and two-year follow-up will study prescribing changes and associations between baseline characteristics/prescribing and subsequent clinical outcomes.

Factors Affecting Early Mortality and 1-Year Outcomes in Young Women With ST-Segment-Elevation Myocardial Infarction Aged Less Than or Equal to 45 Years.

Given that up to 2% of patients with myocardial infarction (MI) are young women, the purpose of this study was to evaluate factors affecting outcomes in young women with ST-segment-elevation myocardial infarction (STEMI) aged less than or equal to 45 years. We evaluated 796 women with STEMI aged less than or equal to 45 years between 2007 and 2014, and mortality was 4.0%. Death occurred more often in women with prehospital sudden cardiac arrest, and severe symptoms of heart failure; less commonly, the women were subjected to percutaneous coronary intervention (PCI), with a higher rate of incomplete revascularization. Beta blockers (BB) and angiotensin converting enzyme inhibitors were frequently used in the survivor group. The independent predictor of 30-day mortality was as follows: inability to undergo PCI (odds ratio [OR] 4.6, 95% confidence interval [CI] 1.45-14.76, P = 0.009), sudden cardiac arrest (OR 4.5, 95% CI 1.5-18.3, P = 0.04). An increase in systolic blood pressure for every 5 mm Hg was associated with lower mortality, OR 0.90, 95% CI 0.76-0.97 in patients without cardiogenic shock (CS) and OR 0.69, 95% CI 0.61-0.78, P < 0.0001 in the group with CS. Predictors for 1-year mortality were the inability to undergo PCI (hazard ratio [HR] 84, 95% CI 1.6-43.1, P = 0.01) and CS (HR 6.97, 95% CI 1.39-34.7, P = 0.01). An increase of 5% in left ventricular ejection fraction reduced the mortality rate for 60% (HR 0.40, 95% CI 0.26-0.63, P < 0.0001) and an increase in systolic blood pressure for every 5 mm Hg reduced mortality for 34% (HR 0.66, 95% CI 0.52-0.84, P = 0.02). Both short- and long-term outcomes in young women aged less than or equal to 45 years with STEMI are good. The strongest predictor for both 30-day and 1-year mortality was the inability to undergo PCI. Suboptimal use of beta blockers and angiotensin converting enzyme inhibitors affect the outcomes in young women. Hypotension in the acute phase of MI increased mortality in young women, independent of coexisting CS.

Differences in Symptomatology and Clinical Course of Acute Coronary Syndromes in Women ≤45 Years of Age Compared to Older Women.

Acute coronary syndromes (ACS) in young people are rare. The data regarding differences in symptoms in relation to age are scarce, which may have an influence on outcomes. The aim of this study was to evaluate the differences in the clinical course of ACS between younger women (≤45 years old) and older women (63-64 years old). We compared 7481 women with ACS from the Polish Registry of ACS between 2007 and 2014 (1834 women aged ≤45 years and 5647 women aged 63-64 years). The predominant symptom of ACS in both groups was chest pain, with a higher incidence occurring in younger women (90.4% vs 88.5%, P = 0.025). Prehospital cardiac arrest occurred more often in younger women (2.1% vs 0.8%, P < 0.001), and onset-to-balloon time was shorter (8.9 vs 15.2 hours, P < 0.0001) in this group. Younger women presented with a lower Killip class at admission (class I at admission: 92.7% vs 86.2%, P < 0.001). The dominant type of ACS in the younger cohort was ST-segment elevation myocardial infarction (STEMI) (42% vs 26.1%), localized mainly in the anterior wall (47.7% vs 36.1%, P < 0.001), with a higher percentage of total occlusion of infarct-related artery (TIMI 0, 45.2% vs 36.1%) and left anterior descending artery engagement for all (33.5% vs 26.5%, P < 0.001). Drug-eluting stents were often used in the younger patients (43.3% vs 38.2%, P = 0.003) without significant differences in percutaneous coronary intervention numbers. Pharmacotherapy was used less in younger women. The 30-day and 2-year mortality in young women was lower than in the older cohort. The clinical course of ACS in younger women differed in comparison to older women. Younger women had a higher occurrence of typical chest pain, STEMI, and left anterior descending artery engagement. Except STEMI patients young women received faster revascularization, however with no significant differences in invasive treatment. Pharmacotherapy was inadequate in younger women and that resulted in a lower usage of the beta-blockers, angiotensin-converting enzyme inhibitors, and statins in that group. Short- and long-term mortality was low, regardless of the type of ACS.

No effects of cardiac resynchronization therapy and right ventricular pacing on the right ventricle in patients with heart failure and atrial fibrillation.

BACKGROUND: The right ventricle (RV) function is crucial in heart failure with reduced ejection fraction (HFrEF), especially in patients with atrial fibrillation (AF). Aims. To assess the RV structure and function in patients with HFrEF, permanent atrial fibrillation (AF), cardiac resynchronization therapy (CRT) and RV pacing (RVp) with two- and three-dimensional echocardiography. Methods. Patients with ischemic HFrEF (NYHA II-III; LVEF ≤40%) were enrolled. The studied groups were: sinus rhythm (SR, control); AF and no implanted devices - AF/0; AF and CRT - AF/CRT; AF and RVp - AF/RVp. Two- and three-dimensional echocardiographic parameters of RV structure and function were analyzed in study groups. Results. The study included a group of 126 patients: n = 32 with SR, n = 28 with AF/0, n = 25 with AF/CRT and n = 41 with AF/RVp. Results were worse in AF groups than in SR: right ventricular ejection fraction, %, mean (SD): SR - 48.2 (7.5), AF/0 - 36.5 (6.5), AF/CRT - 38.3 (7.6), AF/RVp - 37.1 (7.7), p < .001. Other parameters lower in AF groups than in SR were: RV end-systolic volume, longitudinal strain of the free wall and tricuspid lateral annular systolic velocity. There were no differences between groups with AF and CRT and RV pacing in other analyzed parameters between AF groups and SR. Conclusions. In heart failure with reduced left ventricular ejection fraction and atrial fibrillation right ventricular pacing and cardiac resynchronization therapy were not associated with modified right ventricular function. Further prospective studies are needed to evaluate prognostic significance of these results.

Patient perspective and safety of remote monitoring of implantable cardioverter-defibrillators in the Polish Nationwide Multicenter Registry: the Medtronic CareLink network evaluation.

BACKGROUND: Remote monitoring of cardiovascular implantable electronic devices allows the assessment of system effectiveness, arrhythmia occurrence, and indirectly, clinical changes. Medical interventions can be performed earlier because of a faster transfer of information to the monitoring site, even in the case of asymptomatic arrhythmias or abnormalities in the operation of the system. AIMS: The aim of the study was to assess the effectiveness of remote monitoring of implantable cardioverter-defibrillators and evaluation in an outpatient setting during 12-month follow -up. METHODS: We analyzed 176 patients at 10 sites (men, 84.1%). The mean (SD) age of the patients was 60.7 (12.5) years (range, 20-86 years), and mean (SD) follow -up period was 405 (70) days (range, 131-723 days). RESULTS: A total of 354 outpatient and 514 remote follow -up visits were conducted. Episodes of arrhythmias and device malfunctions were detected with similar frequency in outpatient visits and in remote visits. During the study period, patient sense of safety increased. More patients preferred joined remote and outpatient visits as the optimal healthcare model. As the patient survey showed, the greatest benefit of the CareLink network was fast intervention and an increased sense of safety. CONCLUSIONS: The strategy of remote monitoring appeared to be feasible, safe, and patient friendly, demonstrating that the majority of patients do not require an additional in -person visit within 1 year from the device implantation just to confirm the proper functioning of the implantable cardioverter--defibrillators.

Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial).

BACKGROUND: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia which increases the risk of thromboembolic complications and impairs quality of life. An important part of a therapeutic approach for AF is sinus rhythm restoration. Antiarrhythmic agents used in pharmacological cardioversion have limited efficacy and potential risk of proarrhythmia. Simultaneously, underlying conditions of AF should be treated (e.g. electrolyte imbalance, increased blood pressure, neurohormonal disturbances, atrial volume overload). There is still the need for an effective and safe approach to increase AF cardioversion efficacy. This randomized, double-blind, placebo-controlled, superiority clinical study is performed in patients with AF in order to evaluate the clinical efficacy of intravenous canrenone in sinus rhythm restoration. METHODS: Eighty eligible patients with an episode of AF lasting less than 48 h are randomized in a 1:1 ratio to receive canrenone or placebo. Patients randomized to a treatment intervention are receiving canrenone intravenously at a dose of 200 mg within 2-3 min. Subjects assigned to a control group obtain the same volume of 0.9% saline within the same time. The primary endpoint includes return of sinus rhythm documented in the electrocardiogram within 2 h after drug or placebo administration. Other endpoints and safety outcomes analyses, due to expected lack of statistical power, are exploratory. DISCUSSION: Current evidence supports renin-angiotensin-aldosterone system (RAAS) inhibition as an upstream therapy in AF management. Excess aldosterone secretion results in proarrhythmic effects. Among the RAAS inhibitors, only canrenone is administered intravenously. Canrenone additionally increases the plasma level of potassium, lowers blood pressure and reduces preload. It has been already used in primary and secondary hyperaldosteronism in the course of chronic liver dysfunction and in heart failure. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03536806. Registered on 25 May 2018.