Case of a patient with heart failure, dilated cardiomyopathy and atrial fibrillation treated with sacubitril/valsartan.

A novel combination consisting of the neprilysin inhibitor, sacubitril, and the angiotensin-receptor blocker, valsartan (belonging to the newly established class of angiotensin receptor/neprilysin inhibitors), was shown to be effective in the treatment of heart failure (HF) by improving patient clinical status, and reducing re-hospitalization rate and mortality. We report a case of a 29 year old male with HF, dilated cardiomyopathy possibly related to myocarditis and atrial fibrillation with reduced ejection fraction. Sacubitril/valsartan treatment was initiated after two years of standard treatment. In two years, therapy with sacubitril/valsartan led to persistence in sinus rhythm, progressive recovery of ejection fraction, functionality and reduction of cardiac volumes. The patient is currently in good condition and has suspended diuretic therapy in the last six months.

Tocainide and metoprolol: an efficacious therapeutic combination in the treatment of premature ventricular beats.

A double-blind crossover study was performed in 20 patients to verify the efficacy of tocainide plus metoprolol in patients with premature ventricular contractions (PVCs) class Lown greater than or equal to 2 (mean frequency greater than or equal to 30/h) judged as being "stable" by at least three basal 24-h Holter ECGs with PVC variation of less than +/- 25%. All 20 patients were submitted to a placebo period; and all were subsequently randomized to therapy with tocainide 1800 mg/day or metoprolol 200 mg/day for 15 days and then to tocainide 1800 mg + metoprolol 200 mg/day or tocainide 1200 mg + metoprolol 200 mg/day for 15 days, followed by a crossover of the two combination treatments. At steady state in every stage we controlled for plasma levels of the drugs, a 24-h Holter recording, and a 12-lead ECG. A modified Lown score was evaluated together with the Lown class. Tocainide (mean plasma level 3.3 +/- 0.7 micrograms/ml) was efficacious in 3 of 8 patients, the modified Lown score decreased from 63 +/- 32 (placebo period) to 42 +/- 27 (p less than 0.01) and Lown 4B arrhythmias were abolished in 3 of 4 patients. Metoprolol (mean plasma level 97.4 +/- 89.6 ng/ml) was efficacious in 2 of 10 patients; the modified Lown score and Lown classes did not change significantly. Administration of tocainide 1200 mg + metoprolol 200 mg obtained a positive response in 9 of 12 patients, the modified Lown score decreased significantly compared with placebo (from 53 +/- 31 to 32 +/- 30, p less than 0.01) and Lown 4B arrhythmias were abolished in 2 of 5 cases. Tocainide 1800 mg plus metoprolol 200 mg was scarcely tolerated owing to neurologic and gastroenteric side effects, and only three patients completed this stage with no better antiarrhythmic results compared to the lower dose. In conclusion, the combination of tocainide at 1200 mg and metoprolol 200 mg is well tolerated, efficacious in a high percentage of patients, and superior to single drug therapy in patients with stable PVCs.

[Pharmacologic cardioversion with propafenone of stable atrial fibrillation of recent onset]. / Cardioversione farmacologica con propafenone di fibrillazione atriale stabile di recente insorgenza.

The efficacy of intravenous propafenone (P) infused at 2 mg/kg in 3 min as a loading dose followed by 0.007 mg/kg/min along 24 hours, in converting atrial fibrillation (AF) was evaluated under continuous electrocardiographic and blood pressure control in 22 patients. In case of inefficacy after a wash out of 24 hours, amiodarone (A) 5 mg/kg in 3 min followed by 1.8 gr/24 hours was infused. AF had to be constant (at least one 24/hour Holter recording) and of recent onset. All the patients were NYHA class 1 or 2. Ten patients reverted to sinus rhythm after P usually within 60 min; two of the non responders reverted after A and ten did not revert at all. RR intervals were significantly shorter in the responders compared to the others: mean value 537 +/- 64 vs 771 +/- 200 msec (p less than 0.001). During P the QRS duration increased 12.9% (p less than 0.005) and QTc of a lesser extent 7.8%; during A QRS did not modify significantly and QTc prolonged 9.5% (p less than 0.002). Propafenone i.v. infusion appears to be a rapid effective method of converting recent onset AF to sinus rhythm in patients with high ventricular rate. Amiodarone i.v. does not significantly help in converting to sinus rhythm the patients non responder to P.

Antiarrhythmic efficacy of propafenone: evaluation of effective plasma levels following single and multiple doses.

In 11 patients with stable premature ventricular beats, the kinetics of single (150 and 300 mg) and multiple (150 mg t.i.d. and 300 mg t.i.d.) oral doses of propafenone were studied with reference to arrhythmia suppression. During the acute phase detectable plasma levels of the drug were achieved only with the higher dose. In 8 out of 10 patients the antiarrhythmic effect was obtained with the 300 mg dose, which was found to predict responsiveness at steady-state. During the chronic phase, antiarrhythmic efficacy was obtained with the lower dose regimen (150 mg t.i.d.) in half of those patients. A wide range of effective plasma levels was observed. The previously suggested therapeutic range (0.5-2.0 micrograms/ml) was not adequate in predicting either antiarrhythmic activity or adverse effects. The results show the role of propafenone metabolites in determining total antiarrhythmic action.