Comparison of Circadian Variation for In-Hospital Versus Out-of-Hospital Sudden Cardiac Arrest Survivors.

Several studies have reported circadian periodicity of sudden cardiac arrest (SCA). It remains unclear to what extent this circadian rhythm is influenced by variation in patients' activities. One way to elucidate this is to compare patients with out-of-hospital cardiac arrests (OHCAs) with those with in-hospital cardiac arrests (IHCAs). We therefore examined the presence of a circadian pattern of SCA in a large cohort of OHCA and IHCA survivors. A total of 1,433 consecutive survivors of SCA in the Pittsburgh area from 2002 to 2012 were included. Patient demographics, including clinical histories and details of SCA, were collected. The distribution of SCA throughout the day was tested for differences using the chi-square test. Of the 1,224 patients analyzed, 706 had IHCA and 518 OHCA. We observed a nadir of SCA in the nighttime hours between 12 a.m. and 6 a.m. in both IHCA and OHCA groups (p <0.001), although this pattern was more blunted in the IHCA group. Patients who had an SCA in the nighttime window had more co-morbidities (p = 0.01). The circadian pattern was noted to be absent in patients with higher co-morbidity burden in IHCA only. In conclusion, the typical pattern of nighttime nadir in SCA is observed in patients with both OHCA and IHCA but is blunted in the hospital and especially in sicker patients. This suggests a common mechanistic pathway of SCA transcending differences in physical activities of patients and a difference in how co-morbidities interact with the timing of SCA in the inpatient setting.

Neuromuscular electrical stimulation is feasible in patients with acute heart failure.

AIMS: In acute heart failure (AHF), immobilization is caused because of unstable haemodynamics and dyspnoea, leading to protein wasting. Neuromuscular electrical stimulation (NMES) has been reported to preserve muscle mass and improve functional outcomes in chronic disease. NMES may be effective against protein wasting frequently manifested in patients with AHF; however, whether NMES can be implemented safely without any adverse effect on haemodynamics has remained unknown. This study aimed to examine the feasibility of NMES in patients with AHF. METHODS AND RESULTS: Patients with AHF were randomly assigned to the NMES or control group. The intensity of the NMES group was set at 10-20% maximal voluntary contraction level, whereas the control group was limited at a visible or palpable level of muscle contraction. The sessions were performed 5 days per week since the day after admission. Before the study implementation, we set the feasibility criteria with following items: (i) change in systolic blood pressure (BP) > ±20 mmHg during the first session; (ii) increase in heart rate (HR) > +20 b.p.m. during the first session; (iii) development of sustained ventricular arrhythmia, atrial fibrillation (AF), and paroxysmal supraventricular tachycardia during all sessions; (iv) incidence of new-onset AF during the hospitalization period < 40%; and (v) completion of the planned sessions by >70% of patients. The criteria of feasibility were set as follows; the percentage to fill one of (i)-(iii) was <20% of the total subjects, and both (iv) and (v) were satisfied. A total of 73 patients (median age 72 years, 51 men) who completed the first session were analysed (NMES group, n = 34; control group, n = 39). Systolic BP and HR variations were not significantly different between two groups (systolic BP, P = 0.958; HR, P = 0.665). Changes in BP > ±20 mmHg or HR > +20 b.p.m. were observed in three cases in the NMES group (8.8%) and five in the control group (12.8%). New-onset arrhythmia was not observed during all sessions in both groups. During hospitalization, one patient newly developed AF in the NMES group (2.9%), and one developed AF (2.6%) and two lethal ventricular arrhythmia in the control group. Thirty-one patients in the NMES group (91%) and 33 patients in the control group (84%) completed the planned sessions during hospitalization. This study fulfilled the preset feasibility criteria. CONCLUSIONS: NMES is feasible in patients with AHF from immediately after admission.

Association of oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin with the risk of serious ventricular arrhythmia: a nationwide cohort study in Korea.

OBJECTIVE: To evaluate whether oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin increase the risk of ventricular arrhythmia in Korea's general population. DESIGN: Population-based cohort study using administrative claims data on a national scale in Korea. SETTING: All primary, secondary and tertiary care settings from 1 January 2015 to 31 December 2015. PARTICIPANTS: Patients who were prescribed the relevant study medications at outpatient visits. PRIMARY OUTCOME MEASURES: Each patient group that was prescribed ciprofloxacin, levofloxacin, ofloxacin or moxifloxacin was compared with the group that was prescribed cefixime to assess the risk of serious ventricular arrhythmia (ventricular tachycardia, fibrillation, flutter and cardiac arrest). Using logistic regression analysis with inverse probability of treatment weighting using the propensity score, OR and 95% CI for serious ventricular arrhythmia were calculated for days 1-7 and 8-14 after the patients commenced antibiotic use. RESULTS: During the study period, 4 888 890 patients were prescribed the study medications. They included 1 466 133 ciprofloxacin users, 1 141 961 levofloxacin users, 1 830 786 ofloxacin users, 47 080 moxifloxacin users and 402 930 cefixime users. Between 1 and 7 days after index date, there was no evidence of increased serious ventricular arrhythmia related to the prescription of ciprofloxacin (OR 0.72; 95% CI 0.49 to 1.06) and levofloxacin (OR 0.92; 95% CI 0.66 to 1.29). Ofloxacin had a 59% reduced risk of serious ventricular arrhythmia compared with cefixime during 1-7 days after prescription. Whereas the OR of serious ventricular arrhythmia after the prescription of moxifloxacin was 1.87 (95% CI 1.15 to 3.11) compared with cefixime during 1-7 days after prescription. CONCLUSIONS: During 1-7 days after prescription, ciprofloxacin and levofloxacin were not associated with increased risk and ofloxacin showed reduced risk of serious ventricular arrhythmia. Moxifloxacin increased the risk of serious ventricular arrhythmia.

A modified approach for programmed electrical stimulation in mice: Inducibility of ventricular arrhythmias.

BACKGROUND: Electrophysiological studies in mice, the prevailing model organism in the field of basic cardiovascular research, are impeded by the low yield of programmed electrical stimulation (PES). OBJECTIVE: To investigate a modified approach for ventricular arrhythmia (VA) induction and a novel scoring system in mice. METHOD: A systematic review of literature on current methods for PES in mice searching the PubMed database revealed that VA inducibility was low and ranged widely (4.6 ± 10.7%). Based on this literature review, a modified PES protocol with 3 to 10 extrastimuli was developed and tested in comparison to the conventional PES protocol using up to 3 extrastimuli in anesthetized wildtype mice (C57BL/6J, n = 12). Induced VA, classified according to the Lambeth Convention, were assessed by established arrhythmia scores as well as a novel arrhythmia score based on VA duration. RESULTS: PES with the modified approach raised both the occurrence and the duration of VA compared to conventional PES (0% vs 50%; novel VA score p = 0.0002). Particularly, coupling of >6 extrastimuli raised the induction of VA. Predominantly, premature ventricular complexes (n = 6) and ventricular tachycardia <1s (n = 4) were observed. Repeated PES after adrenergic stimulation using isoprenaline resulted in enhanced induction of ventricular tachycardia <1s in both protocols. CONCLUSION: Our findings suggest that the presented approach of modified PES enables effective induction and quantification of VA in wildtype mice and may well be suited to document and evaluate detailed VA characteristics in mice.

Progression of late postoperative atrial fibrillation in patients with tetralogy of Fallot.

INTRODUCTION: ToF patients are at risk for ventricular deterioration at a relatively young age, which can be aggravated by AF development. Therefore, knowledge on AF development and its timespan of progression is essential to guide treatment strategies for AF. OBJECTIVE: We examined late postoperative AF onset and progression in ToF patients during long-term follow-up after ToF correction. In addition, coexistence of AF with regular supraventricular tachyarrhythmias (SVT) and ventricular tachyarrhythmias (VTA) was analyzed. METHODS AND RESULTS: ToF patients (N  =  29) with AF after ToF correction referred to the electrophysiology department between 2000 and 2015 were included. All available rhythm registrations were reviewed for AF, regular SVT, and VTA. AF progression was defined as transition from paroxysmal AF to (longstanding) persistent/permanent AF or from (longstanding) persistent AF to permanent AF. At the age of 44 ± 12 years, ToF patients presented with paroxysmal (N  =  14, 48%), persistent (N  =  13, 45%) or permanent AF (N  =  2, 7%). Age of AF development was similar among patients who either underwent initial shunt creation (N  =  15, 45 ± 11 [25-57] years) or primary total ToF correction (N  =  14, 43 ± 13 [26-66] years) (P  =  0.785). AF coexisted with regular SVT (N  =  18, 62%) and VTA (N  =  13, 45%). Progression of AF occurred in 11 patients (38%) within 5 ± 5 years after AF onset despite antiarrhythmic drug class II (AAD, P  =  0.052) or III (P  =  0.587) usage. CONCLUSIONS: AF in our ToF population developed at a young age and showed rapid progression. Rhythm control by pharmacological therapy was ineffective in preventing AF progression.

Implantable Cardioverter-Defibrillator Therapy in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Predictors of Appropriate Therapy, Outcomes, and Complications.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is characterized by ventricular arrhythmias and sudden cardiac death. Once the diagnosis is established, risk stratification to determine whether implantable cardioverter-defibrillator (ICD) placement is warranted is critical. METHODS AND RESULTS: The cohort included 312 patients (163 men, age at presentation 33.6±13.9 years) with definite arrhythmogenic right ventricular dysplasia/cardiomyopathy who received an ICD. Over 8.8±7.33 years, 186 participants (60%) had appropriate ICD therapy and 58 (19%) had an intervention for ventricular fibrillation/flutter. Ventricular tachycardia at presentation (hazard ratio [HR]: 1.86; 95% confidence interval [CI], 1.38-2.49; P<0.001), inducibility on electrophysiology study (HR: 3.14; 95% CI, 1.95-5.05; P<0.001), male sex (HR: 1.62; 95% CI, 1.20-2.19; P=0.001), inverted T waves in ≥3 precordial leads (HR: 1.66; 95% CI, 1.09-2.52; P=0.018), and premature ventricular contraction count ≥1000/24 hours (HR: 2.30; 95% CI, 1.32-4.00; P=0.003) were predictors of any appropriate ICD therapy. Inducibility at electrophysiology study (HR: 2.28; 95% CI, 1.10-4.70; P=0.025) remained as the only predictor after multivariable analysis. The predictors for ventricular fibrillation/flutter were premature ventricular contraction ≥1000/24 hours (HR: 4.39; 95% CI, 1.32-14.61; P=0.016), syncope (HR: 1.85; 95% CI, 1.10-3.11; P=0.021), aged ≤30 years at presentation (HR: 1.76; 95% CI, 1.04-3.00; P<0.036), and male sex (HR: 1.73; 95% CI, 1.01-2.97; P=0.046). Younger age at presentation (HR: 3.14; 95% CI, 1.32-7.48; P=0.010) and high premature ventricular contraction burden (HR: 4.43; 95% CI, 1.35-14.57; P<0.014) remained as independent predictors of ventricular fibrillation/flutter. Complications occurred in 66 participants (21%), and 64 (21%) had inappropriate ICD interventions. Overall mortality was low at 2%, and 4% underwent heart transplantation. CONCLUSION: These findings represent an important step in identifying predictors of ICD therapy for potentially fatal ventricular fibrillation/flutter and should be considered when developing a risk stratification model for arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Comparative Risk of Ventricular Arrhythmia and Sudden Cardiac Death Across Antidepressants in Patients With Depressive Disorders.

OBJECTIVE: We aimed to evaluate the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with antidepressant use. METHODS: A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 793,460 new antidepressant users with depressive disorders were enrolled in the study. Outcomes were defined as the first principal diagnosis of VA or SCD in the emergency department or hospital discharge records. Cox proportional hazards models with stratification of propensity score deciles were used to evaluate the relative risk of VA/SCD for antidepressants compared with selective serotonin reuptake inhibitors (SSRIs). RESULTS: A total of 245 VA/SCD events occurred. The incidence rate of VA/SCD among antidepressant users was 1.5 per 1000 person-years (95% confidence interval [CI], 1.3-1.7). Compared with SSRIs, the risk of VA/SCD was significantly lower for tricyclic or tetracyclic antidepressant (TCAs) (adjusted hazards ratio [aHR], 0.54; 95% CI, 0.36-0.83), but not other antidepressant classes. However, use of moderate- to high-dose TCAs carried a higher risk than low-dose TCAs (aHR, 4.37; 95% CI, 1.23-15.60). Antidepressant polypharmacy was associated with an increased risk of VA/SCD (aHR, 1.63; 95% CI, 1.07-2.49). CONCLUSIONS: There was no difference in VA/SCD risk across antidepressant classes except that TCAs were associated with a lower risk than SSRIs. However, the observed comparative risk of TCAs might be attributable to low-dose TCA use, which is quite common in current clinical practice. It would be of importance to carry out further investigations to scrutinize the influence of antidepressants on VA/SCD.

Management of ventricular arrhythmias in structural heart disease.

Ventricular arrhythmias (VA) are a source of significant morbidity and mortality in patients with structural heart disease (SHD). The advent of the implantable cardiac defibrillator (ICD) has had a positive effect on mortality, but the associated morbidity remains a significant problem. Modern treatment of VA has advanced far beyond medical therapy and includes strategies as simple as intelligent ICD programming and as complex as catheter ablation (CA). In these pages, the spectrum of management strategies will be discussed; from anti-arrhythmic drugs and ICD implantation and programming to CA and autonomic modulation. The focus of this review will be on strategies for secondary prevention of VA in patients with SHD, supported by clinical evidence for their utilization.

Subcutaneous nerve activity and spontaneous ventricular arrhythmias in ambulatory dogs.

BACKGROUND: Stellate ganglion nerve activity (SGNA) is important in ventricular arrhythmogenesis. However, because thoracotomy is needed to access the stellate ganglion, it is difficult to use SGNA for risk stratification. OBJECTIVE: The purpose of this study was to test the hypothesis that subcutaneous nerve activity (SCNA) in canines can be used to estimate SGNA and predict ventricular arrhythmia. METHODS: We implanted radiotransmitters to continuously monitor left stellate ganglion and subcutaneous electrical activities in 7 ambulatory dogs with myocardial infarction, complete heart block, and nerve growth factor infusion to the left stellate ganglion. RESULTS: Spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) was documented in each dog. SCNA preceded a combined 61 episodes of VT and VF, 61 frequent bigeminy or couplets, and 61 premature ventricular contractions within 15 seconds in 70%, 59%, and 61% of arrhythmias, respectively. Similar incidence of 75%, 69%, and 62% was noted for SGNA. Progressive increase in SCNA [48.9 (95% confidence interval [CI] 39.3-58.5) vs 61.8 (95% CI 45.9-77.6) vs 75.1 (95% CI 57.5-92.7) mV-s] and SGNA [48.6 (95% CI 40.9-56.3) vs 58.5 (95% CI 47.5-69.4) vs 69.0 (95% CI 53.8-84.2) mV-s] integrated over 20-second intervals was demonstrated 60 seconds, 40 seconds, and 20 seconds before VT/VF (P <.05), respectively. The Pearson correlation coefficient for integrated SCNA and SGNA was 0.73 ± 0.18 (P <.0001 for all dogs, n = 5). Both SCNA and SGNA exhibited circadian variation. CONCLUSION: SCNA can be used as an estimate of SGNA to predict susceptibility to VT and VF in a canine model of ventricular arrhythmia and sudden cardiac death.

A historical review of trauma-related diagnoses to reconsider the heterogeneity of PTSD.

Based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders, there are 636,120 ways for an individual to qualify for a diagnosis of posttraumatic stress disorder (PTSD) (Galatzer-Levy & Bryant, 2013). To unravel this heterogeneity, we examine the historical trajectory of trauma-related diagnoses. Our review addresses four traumas (i.e., combat, natural disaster, life-threatening accident and sexual assault) that have contributed the most to conceptual models of PTSD. Although these trauma types are all subsumed under the same diagnostic label, our literature review indicates that the psychological consequences of different traumatic experiences are traditionally studied in isolation. Indeed, most research addresses hypotheses regarding specific trauma types using samples of individuals selected for their experience with that specific event. We consider the possibility that PTSD is not a single, unified construct and what this means for future research and clinical applications.

Influence of the mode of management of acute myocardial infarction on the inducibility of ventricular tachyarrhythmias with programmed ventricular stimulation after myocardial infarction.

BACKGROUND: Programmed ventricular stimulation (PVS) is a technique for screening patients at risk for ventricular tachycardia (VT) after myocardial infarction (MI), but the results might be difficult to interpret. OBJECTIVES: To investigate the results of PVS after MI, according to date of completion. METHODS: PVS results were interpreted according to the mode of MI management in 801 asymptomatic patients: 301 (group I) during the period 1982-1989, 315 (group II) during 1990-1999, and 185 (group III) during 2000-2010. The periods were chosen based on changes in MI management. Angiotensin-converting enzyme (ACE) inhibitors had been given since 1990; primary angioplasty was performed routinely since 2000. The PVS protocol was the same throughout the whole study period. RESULTS: Group III was older (61 +/- 11 years) than groups I (56 +/- 11) and II (58 +/- 11) (P < 0.002). Left ventricular ejection fraction (LVEF) was lower in group III (36.5 +/- 11%) than in groups I (44 +/- 15) and II (41 +/- 12) (P < 0.000). Monomorphic VT < 270 beats/min was induced as frequently in group III (28%) as in group II (22.5%) but more frequently than in group I (20%) (P < 0.03). Ventricular fibrillation and flutter (VF) was induced less frequently in group III (14%) than in groups I (28%) (P < 0.0004) and II (30%) (P < 0.0000). Low left ventricular ejection fraction (LVEF) and date of inclusion (before/after 2000) were predictors of VT or VF induction on multivariate analysis. CONCLUSIONS: Induction of non-specific arrhythmias (ventricular flutter and fibrillation) was less frequent than before 2000, despite the indication of PVS in patients with lower LVEF. This decrease could be due to the increased use of systematic primary angioplasty for MI since 2000.

Long-term arrhythmia-free survival in patients with severe left ventricular dysfunction and no inducible ventricular tachycardia after myocardial infarction.

BACKGROUND: A negative electrophysiology study (EPS) may delineate a subgroup of patients with severely impaired left ventricular ejection fraction (LVEF) whose care can be safely managed long-term without an implantable cardioverter-defibrillator. METHODS AND RESULTS: Consecutive patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction underwent early (median 4 days) LVEF assessment. Patients with LVEF ≤40% underwent EPS. A prophylactic implantable cardioverter-defibrillator was implanted for a positive (inducible monomorphic ventricular tachycardia) but not a negative (no inducible ventricular tachycardia or inducible ventricular fibrillation/flutter) EPS result. Patients who would have become eligible for a late primary prevention implantable cardioverter-defibrillator with LVEF ≤30% or ≤35% with New York Heart Association class II/III heart failure were included and analyzed according to EPS result. Patients with LVEF >40%, ineligible for EPS, were followed up as control subjects (n=1286). The primary end point was survival free of death or arrhythmia (resuscitated cardiac arrest or sustained ventricular tachycardia/ventricular fibrillation). EPS performed in 128 patients with LVEF ≤30% or with LVEF ≤35% and heart failure was negative in 63% (n=80) and positive in 37% (n=48). Implantable-cardioverter defibrillators were implanted in <0.1%, 4%, and 90% of control, EPS-negative, and EPS-positive patients, respectively. The distribution of time to death or arrhythmia was comparable in control patients and EPS-negative patients with LVEF ≤30% or with LVEF ≤35% and heart failure (P=0.738), who both differed significantly from EPS-positive patients (P<0.001). At 3 years, 91.8 ± 3.2%, 93.4 ± 1.0%, and 62.7 ± 7.5% of control, EPS-negative, and EPS-positive patients were free of death or arrhythmia, respectively. CONCLUSIONS: Revascularized patients with ST-segment-elevation myocardial infarction with severely impaired left ventricular function but no inducible ventricular tachycardia have a favorable long-term prognosis without the protection of an implantable cardioverter-defibrillator.

Episodic syncope caused by ventricular flutter in a tiger (Panthera tigris).

A captive, 9-yr-old castrated male tiger (Panthera tigris) from an exotic cat sanctuary and rescue facility was observed to have three collapsing episodes within a 2-wk interval prior to being examined by veterinarians. No improvement in clinical signs was noted after empiric treatment with phenobarbital. During a more complete workup for epilepsy, ventricular flutter was observed on electrocardiogram (ECG). The arrhythmia resolved with a single intravenous bolus of lidocaine. Cardiac structure and function were unremarkable on echocardiogram and cardiac troponin I levels were within normal limits for domestic felids. No significant abnormalities were noted on abdominal ultrasound. Complete blood count and biochemistry panel were unremarkable, and heartworm antigen and Blastomyces urine antigen enzyme-linked immunosorbent assays were negative. Antiarrhythmic treatment with sotalol was initiated. On follow-up ECG performed 1 mo later, no significant arrhythmias were noted, and clinical signs have completely resolved.