Emmanuel N. Simantirakis

Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

Long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP), a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversion back to normal following removal of the stressor. The most common environmental stressor in acquired long QT syndrome is drug therapy. Acquired long QT syndrome is an important issue for clinicians and a significant public health problem concerning the large number of drugs with this adverse effect with a potentially fatal outcome, the large number of patients exposed to these drugs, and our inability to predict the risk for a given individual. In this paper, we focus on mechanisms underlying QT prolongation, risk factors for torsades de pointes and describe the short- and long-term treatment of acquired long QT syndrome.

Absence of atherosclerotic lesions in the thoracic aorta indicates absence of significant coronary artery disease

Atherosclerotic lesions may be readily visualized in the thoracic aorta using transesophageal echocardiography. The absence of aortic plaque in the thoracic aorta rules out significant coronary artery obstruction whereas the existence of the former appears to be a sensitive and specific predictor of the latter.

Sleep patterns in patients with acute coronary syndromes

BACKGROUND Little is known about sleep quality in patients with acute coronary syndromes (ACS) admitted to the coronary care unit (CCU). The aim of this study was to assess nocturnal sleep in these patients, away from the CCU environment, and to evaluate potential connections with the disease process. METHODS Twenty-two patients with first ever ACS, who were not on sedation or inotropes, underwent a full-night polysomnography (PSG) in our sleep disorders unit within 3 days of the ACS and follow-up PSGs 1 and 6 months later. RESULTS PSG parameters showed a progressive improvement over the study period. There was a statistically significant increase in total sleep time (TST), sleep efficiency, slow wave sleep (SWS), and rapid eye movement (REM) sleep, while arousal index, wake after sleep onset (WASO) and sleep latency decreased. Six months after the acute event, sleep architecture was within the normal range. CONCLUSIONS Patients with ACS have marked alterations in sleep macro- and micro-architecture, which have a negative influence on sleep quality. The changes tend to disappear over time, suggesting a relationship with the acute phase of the underlying disease.

Intravenous Propafenone Versus Intravenous Amiodarone in the Management of Atrial Fibrillation of Recent Onset: A Placebo-Controlled Study

The efficacy and safety of intravenous propafenone, amiodarone, or placebo were compared in the treatment of atrial fibrillation (AF) of recent onset (duration ≤ 48 hours). Methods: 143 patients (77 men, mean age 63 ± 12 years) were studied, of whom 46 received propafenone (2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours), 48 received amiodarone (300 mg intravenously over 1 hour, followed by 20 mg/kg over the next 24 hours, plus 1,800 mg/day orally, in 3 divided doses), and 49 received placebo (the equivalent amount of saline IV over 24 hours). Digoxin was administered to all patients who had not previously received it. Results: Conversion to normal sinus rhythm occurred in 36 of 46 patients (78.2%) receiving propafenone, in 40 of 48 patients (83.3%) receiving amiodarone, and in 27 of the 49 (55.10%) controls (P < 0.02, drug vs placebo, between drugs NS). The mean time to conversion was 2 ± 3 hours for propafenone, 7 ± 5 hours for amiodarone, and 13 ± 9 for placebo (P < 0.05). Patients who converted had smaller atria than those who did not (diameter: 42.7 ± 5 vs 47.2 ± 7 mm, P < 0.001 for all). Treatment was discontinued in one patient in the amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening. No side effects were observed in the placebo group. Conclusions: Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent‐onset atrial fibrillation to sinus rhythm. However, propafenone offered the advantage of more rapid conversion than amiodarone.

Sleep Disordered Breathing in Patients with Acute Coronary Syndromes

STUDY OBJECTIVES Although the prevalence of obstructive sleep apnea/hypopnea syndrome (OSAHS) is high in patients with acute coronary syndromes (ACS), there is little knowledge about the persistence of OSAHS in ACS patients after the acute event. We aimed to assess the prevalence and time course of OSAHS in patients with ACS during and after the acute cardiac event. METHODS Fifty-two patients with first-ever ACS, underwent attended overnight polysomnography (PSG) in our sleep center on the third day after the acute event. In patients with an apnea hypopnea index (AHI) > 10/h, we performed a follow up PSG 1 and 6 months later. RESULTS Twenty-eight patients (54%) had an AHI > 10/h. There was a significant decrease in AHI 1 month after the acute event (13.9 vs. 19.7, p = 0.001), confirming the diagnosis of OSAHS in 22 of 28 patients (79%). At 6-month follow-up, the AHI had decreased further (7.5 vs. 19.7, p < 0.05), and at that time only 6 of the 28 patients (21%) were diagnosed as having OSAHS. Twelve of the 16 current smokers stopped smoking after the acute event. CONCLUSIONS We have demonstrated a high prevalence of OSAHS in ACS patients, which did not persist 6 months later, indicating that, to some degree, OSAHS may be transient and related with the acute phase of the underlying disease or the reduction in the deleterious smoking habit.

AAIR Versus DDDR Pacing in Patients with Impaired Sinus Node Chronotropy: An Echocardiographic and Cardiopulmonary Study

The aim of this study was to compare AAIR and DDDR pacing at rest and during exercise. We studied 15 patients (10 men, age 65 ± 6 years) who had been paced for at least 3 months with activity sensor rate modulated dual chamber pacemakers. All had sick sinus syndrome (SSS) with impaired sinus node chronotropy. The patients underwent a resting echocardiographic evaluation of systolic and diastolic LV function at 60 beats/min during AAIR and DDDR pacing with an AV delay, which ensured complete ventricular activation capture. Cardiac output (CO) was also measured during pacing at 100 beats/min in both pacing modes. Subsequently, the oxygen consumption (VO2at) and VO2at pulse at the anaerobic threshold were measured during exercise in AAIR mode and in DDDR mode with an AV delay of 120 ms. The indices of diastolic function showed no significant differences between the two pacing modes, except for patients with a stimulus‐R interval > 220 ms, for whom the time velocity integral of LV filling and LV inflow time were significantly lower under AAI than under DDD pacing. At 60 beats/min, CO was higher under AAI than under DDD mode only when the stimulus‐R interval was below 220 ms. For stimulus‐R intervals longer than 220 ms, and also during pacing at 100 beats/min, the CO was higher in DDD mode. The stimulus‐R interval decreased in all patients during exercise. The time to anaerobic threshold, VO2at ond VO2at pulse showed no significant differences between the two pacing modes. Our results indicate that, at rest, although AAIR pacing does not improve diastolic function in patients with SSS, it maintains a higher CO than does DDDR pacing in cases where the stimulus‐R interval is not excessively prolonged. On exertion, the two pacing modes appear to be equally effective, at least in cases where the stimulus‐R interval decreases in AAIR mode.

Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6) trial

Background Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation (AF). Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients. Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not known. Rationale Stroke risk is higher in pacemaker patients with AHRE than in those without, but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF. Furthermore, only a minority of patients with AHRE will develop AF, many strokes occur without a temporal relation to AHRE, and AHRE can reflect other arrhythmias than AF or artifacts. An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed. Design The Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence‐based indications. The primary safety outcome will be major bleeding. NOAH–AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF, aged ≥65 years with at least 1 other stroke risk factor, to oral anticoagulation therapy (edoxaban) or no anticoagulation. All patients will be followed until the end of this investigator‐driven, prospective, parallel‐group, randomized, event‐driven, double‐blind, multicenter phase IIIb trial. Patients will be censored when they develop AF and offered open‐label anticoagulation. The sponsor is the Atrial Fibrillation NETwork (AFNET). The trial is supported by the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research), and Daiichi Sankyo Europe. Conclusion NOAH–AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices. Graphical abstract Figure. No Caption available.

Autonomic nervous system changes in vasovagal syncope: is there any difference between young and older patients?

Spectral analysis of heart rate variability was used to compare the changes in autonomic function during tilting in young and older patients with vasovagal syncope. Twenty‐four young (age 28 ± 8 years) and 31 older (56 ± 5 years) patients with unexplained syncope and a positive tilt test and 25 controls (age 48 ± 12 years) were included in the study. Frequency‐domain measurements of the low (LF) (0.06–0.15 Hz) and high (HF) (0.15–0.40 Hz) frequency bands and the ratio of LF to HF were computed from Holter recordings for 4‐minute intervals before and immediately after tilting and just before the end in all groups. Syncopal patients showed a different pattern of response to tilting from controls in all spectral indexes. Young and older patients showed the same pattern of changes in all measurements, even though certain differences were observed. The LF after tilting reduced more in the older (‐20 ± 7% vs ‐14 ± 5%, P < 0.001), while HF reduced more in young patients (‐17 ± 8% vs ‐8 ± 3%, P < 0.001). Young patients showed mainly a cardioinhibitory type (71%) of response whereas a vasodepressor type response predominated (68%) in the older patients. The autonomic nervous system appears to play an important role in the pathophysiological mechanism of vasovagal syncope. This role is similar in young and in older patients and this should be taken into account in the therapeutic approach to the condition. Specific differences between age groups may be related to the type of vasovagal syncope.

Autonomic Nervous System Activity Before and During Episodes of Myocardial Ischemia in Patients with Stable Coronary Artery Disease During Daily Life

Spectral analysis of heart rate variability (HR V) was used to assess changes in the autonomic nervous system (ANS) 10 minutes before, during, and 10 minutes after 110 ischemic episodes (IEs) in 38 patients (25 men, age 61 ± 10 years) with stable coronary artery disease. In 26 of 77 diurnal IEs (07:00–22:59) there were no changes in the spectral indexes (LF and HF) during the study period. In the remainder there was an increase in the LF:HF ratio due to HF withdrawal that started before the onset of the IE. AII 33 nocturnal episodes also showed an increase in the LF:HF ratio, which was due not only to HF withdrawal, but also to a simultaneous increase in LF. Although it is not the only cause, the ANS plays a significant role in triggering IEs during daily life in patients with stable coronary artery disease. The common factor in all such episodes is a gradual withdrawal of parasympathetic tone.

Assessment of autonomic function at rest and during tilt testing in patients with vasovagal syncope

This study evaluated autonomic nervous system function in 30 patients with syncope and a positive tilt test result, 20 with a negative test result, and 20 healthy controls. Indexes of heart rate variability were measured during the intervals immediately before and after tilt, while all subjects were asymptomatic, and over a 24-hour period. There were no significant differences among the groups in any of the indexes of heart rate variability over the 24-hour period. In patients with a positive tilt result, tilting caused a decrease in low-frequency (LF) and high-frequency (HF) bands, although the LF/HF ratio did not significantly change. In patients with a negative tilt result there was a decrease in the HF band but no other significant changes. In the controls there was an increase in the LF band and LF/HF ratio and a decrease in the HF band. Our findings showed that patients with vasovagal syncope have no chronic differences from normal subjects in autonomic nervous system activity, but that these patients respond differently to the orthostatic stimulus.