No abstract

Dronedarone is an amiodarone analog but differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These modifications reduced thyroid and other end-organ adverse effects and makes dronedarone less lipophilic, shortening its half-life. Dronedarone has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi-center trials. In addition to its rhythm control properties, dronedarone has rate control properties and slows the ventricular response during AF. Dronedarone is approved in Europe for rhythm and rate control indications. In patients with decompensated heart failure, dronedarone treatment increased mortality and cardiovascular hospitalizations. However, when dronedarone was used in elderly high risk AF/AFl patients excluding such high risk heart failure, cardiovascular hospitalizations were significantly reduced and the drug was approved in the USA for this indication in 2009 by the Food and Drug Administration. Updated guidelines suggest dronedarone as a front-line antiarrhythmic in many patients with AF/Fl but caution that the drug should not be used in patients with advanced heart failure. In addition, the recent results of the PALLAS trial suggest that dronedarone should not be used in the long-term treatment of patients with permanent AF.

Dofetilide is more effective in patients with persistent than in those with paroxysmal AF/AFL. Importantly, short-term response does not necessarily predict long-term efficacy. Significant proarrhythmia can occur even with careful in-hospital monitoring.

In patients with an ICD and ventricular arrhythmias, dofetilide decreases the frequency of VT/VF and ICD therapies even when other antiarrhythmic agents, including amiodarone, have previously been ineffective. Recurrences still occur in some patients requiring catheter ablation, mechanical support, or heart transplantation.

The absence of respiratory movements is a major criterion recommended for use by bystanders for recognizing an out-of-hospital cardiac arrest (CA), as the persistence of eupneic breathing is considered to be incompatible with CA. The basis for CA-related apnea is, however, uncertain, since brain stem Po(2) is not expected to drop immediately to the critical level where anoxic apnea occurs. It is therefore essential on both clinical and physiological grounds to determine whether and when breathing stops after the onset of CA. In eight patients, we measured the ventilatory response at the onset of ventricular fibrillation (VF) for 12-15 s during the placement of an implantable cardioverter-defibrillator device. We found that regular eupneic breathing was maintained unchanged despite the cessation of systemic and pulmonary blood flow generated by the heart. We extended these findings in adult sheep and found that, as in humans, the normal ventilatory pattern persists unchanged for the first 15 s despite the drop in blood pressure, followed by a progressive increase in minute ventilation, which was sustained for up to 164 s. The ensuing apnea was disrupted by typical gasps occurring at a very slow frequency. These observations suggest a complete "decoupling" between the return of CO(2) to the pulmonary circulation and continued effective respiratory activity, contrary to what we predicted. This delayed cessation of eupneic breathing during the absence of cardiac pump function is likely related to the time needed for brain stem anoxia to develop. These findings challenge the notions that 1) ventilation stops as pulmonary blood flow/cardiac output ceases and 2) the presence of eupneic breathing is a reliable sign of effective cardiac pumping activity.