Massimo Santini

Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids After Myocardial Infarction

Background— Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. Methods and Results— In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0...

Electrophysiological Characteristics of the Human Atria After Cardioversion of Persistent Atrial Fibrillation

BACKGROUNDnIn animal models, induced atrial fibrillation shortens the atrial effective refractory period (ERP) and reverses its physiological adaptation to rate. It is not clear whether this process, known as electrical remodeling, occurs in humans.nnnMETHODS AND RESULTSnWe determined the ERPs, at 5 pacing cycle lengths (300 to 700 ms) and in 5 right atrial sites, after internal cardioversion of chronic atrial fibrillation in 25 patients (14 in pharmacological washout and 11 on amiodarone). The ERPs were 195.5+/-18.8 ms in the washout and 206.3+/-17.9 ms in the amiodarone patients (P<0.0001). ERPs were closely correlated with the stimulation rates (r=0.95 in the washout and r=0.94 in the amiodarone group), and slope values indicating a normal (>/=0.07) or nearly normal (0.05 to 0.06) adaptation of ERP to rate were found in 77% of the 84 paced sites. The mean ERP was shorter in the lateral wall (198.1+/-17.9 ms) than in the atrial roof (203.3+/-21.5 ms) and in the septum (210.5+/-20.0 ms) (P<0.03). After 4 weeks of sinus rhythm, the mean ERP, determined again in 8 patients (4 in wash-out and 4 on amiodarone), was significantly increased compared with the basal study (221. 4+/-21.4 versus 197.8+/-18.3 ms, P<0.0001).nnnCONCLUSIONSnAfter cardioversion of chronic atrial fibrillation, (1) atrial ERP adaptation to rate was normal or nearly normal in the majority of the cases, (2) a significant dispersion of refractoriness between different right atrial sites was present, and (3) ERPs were significantly increased after 4 weeks of sinus rhythm in both washout and amiodarone patients.

Local Capture by Atrial Pacing in Spontaneous Chronic Atrial Fibrillation

BACKGROUNDnAtrial fibrillation (AF) is considered to be maintained by multiple reentrant circuits without or with a very short excitable gap. However, the possibility of local atrial capture has been shown recently in experimental AF or induced AF in humans.nnnMETHODS AND RESULTSnThis study was undertaken to evaluate the feasibility of atrial capture-suggestive of an excitable gap-in spontaneous chronic AF. Decremental pacing was performed in 47 right atrial sites in 14 patients with chronic AF, not taking antiarrhythmic drugs. A Franz catheter (for pacing and monophasic action potential recording) and a recording quadripolar catheter positioned about 10 mm apart were used. Local capture was achieved in 41 (87.2%) sites for a total of 100 captures. In 71 episodes the capture was lost within 15 seconds, while in the remaining 29, pacing was stopped after 15 seconds of stable capture. AF types immediately before capture were type 1 in 83 and type 2 in 17 episodes. Type 3 AF was never captured. Pacing cycle at capture was 175.7 +/- 20.9 ms. The baseline atrial interval (FF) was 185.4 +/- 24.5, significantly longer than the FF recorded during pacing immediately before capture (176.0 +/- 19.8 ms) (P < .02).nnnCONCLUSIONSnDuring spontaneous chronic AF in humans, (1) local capture by atrial pacing is possible up to at least 15 mm from the pacing site, (2) regional entrainment is possible during type 1 and type 2 AF but not type 3 AF, and (3) pacing before capture accelerates AF, probably by transient or local capture. These findings suggest that an excitable gap is present in chronic AF, therefore supporting the hypothesis that leading circle reentry is not the unique electrophysiological mechanism maintaining the arrhythmia.

Direct oral anticoagulants in patients undergoing cardioversion: insight from randomized clinical trials

Anticoagulation, reducing the risk of thromboembolic events in patients undergoing cardioversion, is a cornerstone of peri-cardioversion management in patients with atrial fibrillation. We aimed to analyse published data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients undergoing cardioversion. We performed a systematic review of randomized prospective clinical trials (RCTs) comparing DOACs with warfarin and reporting data on post-cardioversion outcomes of interest. Outcomes of interest were stroke, systemic thromboembolic events and major bleeding. We reviewed a total of six RCTs including 3900 cardioversions performed using a DOAC for thromboembolic prophylaxis. These studies reported a low incidence overall of adverse outcomes associated with the use of DOACs (around 1% in all studies, except the ROCKET post-hoc study which included ablation procedures). The incidence rate of adverse events during DOAC treatment was found to be very similar to that observed with warfarin anticoagulation. In RCTs DOAC treatment in patients undergoing cardioversion appears to be effective and safe. However, because evidence in this clinical setting is still weak, observational reports could be useful in providing further data about peri-procedural outcomes.

Psycho-educational Interventions and Cardiac Rehabilitation

Lifestyle and emotional mindset, as well as patient education about the disease, play a critical role in ischaemic heart disease (IHD) outcomes. A psycho-educational approach aims to treat the patient as a whole by emphasizing patient education and empowerment, as well as offering psychological support based on individual needs. In this chapter, we address the clinical impact of a healthy lifestyle on IHD, emphasizing behavioural modification when necessary. We report recommendations for physical activity and diet that have been confirmed in the setting of IHD and then summarize the interventions aimed at smoking cessation and the management of psychological disorders. The last paragraph briefly discusses the role of cardiac rehabilitation, pointing out the relevance of addressing psychosocial disorders in order to increase the benefits of cardiac rehabilitation.

Can Pacing be More Physiological

Although the superiority of dual-chamber (DDD) pacing in terms of haemodynamic and clinical benefits has well been established compared to single-chamber ventricular (VVI) pacing modality, especially in some conditions such as recurrent atrial tachyarrhythmias and congestive heart failure, much still remains to be done to reach a truly physiological way of pacing the human heart. The optimal pacing system should mimic the native physiological functioning of the conduction system as closely as possible. In reality, current pacing systems are far from reproducing the function of the normal heart. If in some cases clinical benefits can paradoxically be obtained by means of an “unphysiological” pacing (e.g. pacing the right ventricular apex to reduce left intraventricular gradient in obstructive cardiomyopathy), in the vast majority of cases pacing with the current technology and configuration produces detrimental effects on several aspects of cardiac functionality, and does not allow maximal benefits to be obtainedl. The normal sequence of electric activation of the ventricles is largely disrupted by pacing the right ventricular apex; the normal sequence of atrial activation is modified by the current method of pacing in the right atrial appendage causing intra-atrial delays; the optimal temporisation of atrial and ventricular contraction would require atrioventricular (AV) delay adjustments; the current single-sensor technology only in part resembles the physiological sinus node response to metabolic, activity and emotional requirements.

Benefits of sensor driven dual chamber pacing

To overcome the limitation of the fixed heart rate of VVI/DDD pacing, devices having a system of sensors able to modify the rate of pulse discharge and to meet the metabolic needs of the patients (DDDR/VVIR pacing) have been tested in several investigations [1–6]. In addition, the superiority of DDDR pacing versus WIR pacing due to the preservation of the a-v synchronism has been proven especially when the atrioventricular (AV) delay is also rate-adaptive [2–6].