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.

QT response after a test dose and during maintenance therapy with AZD1305 in patients with atrial fibrillation: a double-blind, randomized, placebo-controlled trial.

BACKGROUND AND OBJECTIVE: AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenance treatment with AZD1305. METHODS: This was a randomized, double-blind, parallel-group, placebo-controlled trial carried out at multiple hospital cardiac facilities in Denmark, Norway, Poland, Slovakia, and Sweden. Patients with documented atrial fibrillation (AF) but currently in stable sinus rhythm for ≥2 hours and ≤90 days were eligible for inclusion. Patients were randomized in a 1 : 1 : 1 ratio to receive AZD1305 extended-release or matching placebo tablets as follows: group A - test dose 250 mg, evening dose 125 mg on day 1, maintenance dose 125 mg twice daily; group B - test dose 500 mg, placebo evening dose, maintenance dose 125 mg twice daily; placebo group - placebo test and maintenance dose. Maintenance dosing was for 9 days. QTcF >550 ms at any time during the in-patient phase or >500 ms after discharge (day 4) were predefined study drug discontinuation criteria. The main outcome measure was the relationship between QTcF following the test dose and during maintenance treatment. RESULTS: Sixty-five patients were randomized (n = 21, 22, and 22 in group A, group B, and the placebo group, respectively). AZD1305 dose-dependently increased QTcF. There was a positive, linear correlation between the change in QTcF during the first 6 hours after the test dose and during the maintenance phase. Three patients, all from group B, discontinued treatment on day 1 due to QTcF >550 ms. All other patients completed the study without events related to QT prolongation. There was a trend for reduced AF recurrence with AZD1305 compared with placebo. CONCLUSION: In this exploratory study a test dose predicted the QT response during maintenance treatment with AZD1305 and may thus be employed in further studies. [ClinicalTrials.gov Identifier: NCT00643448].

[Short QT syndrome--a case report]. / Zespól skróconego odstepu QT--opis przypadku.

We present two new cases of the short QT syndrome--a 23-year-old male and his 42-year-old mother. Invasive electrophysiological study was negative in both patients. Due to polymorphic ventricular tachycardia recorded during Holter ECG monitoring, an ICD was implanted in the male patient for primary prevention. Blood samples were collected for further genetic studies. Diagnosis and management of patients with the short QT syndrome are discussed.