Symbiotic cardiac pacemaker.

Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm shift that is on the horizon. Here, we demonstrate a fully implanted symbiotic pacemaker based on an implantable triboelectric nanogenerator, which achieves energy harvesting and storage as well as cardiac pacing on a large-animal scale. The symbiotic pacemaker successfully corrects sinus arrhythmia and prevents deterioration. The open circuit voltage of an implantable triboelectric nanogenerator reaches up to 65.2 V. The energy harvested from each cardiac motion cycle is 0.495 µJ, which is higher than the required endocardial pacing threshold energy (0.377 µJ). Implantable triboelectric nanogenerators for implantable medical devices offer advantages of excellent output performance, high power density, and good durability, and are expected to find application in fields of treatment and diagnosis as in vivo symbiotic bioelectronics.

Sinus Bradycardia in Habitual Cocaine Users.

Common physiological manifestations of cocaine are related to its adrenergic effects, due to inhibition of dopamine and norepinephrine uptake at the postsynaptic terminal. Few studies have documented bradycardia secondary to cocaine use, representing the antithesis of its adrenergic effects. We assessed the prevalence of sinus bradycardia (SB) in habitual cocaine users and postulated a mechanism for this effect. One hundred sixty-two patients with a history of cocaine use were analyzed and compared with age- and gender-matched controls. SB was defined as a rate of <60 beats/min and habitual cocaine use as 2 or more documented uses >30 days apart. Propensity score-matching analysis was applied to balance covariates between cocaine users and nonusers and reduce selection bias. Patients with a history of bradycardia, hypothyroidism, or concomitant beta-blocker use were excluded. Mean age of study patients was 44 ± 8 years. SB was observed in 43 of 162 (27%) cocaine users and in 9 of 149 (6%) nonusers (p = 0.0001). Propensity score-matching analysis matched 218 patients from both groups. Among matched patients SB was observed in 25 of 109 (23%) cocaine users and in 5 of 109 (5%) nonusers (p = 0.0001). Habitual cocaine use was an independent predictor of SB and associated with a sevenfold increase in the risk of SB (95% CI 2.52 to 19.74, p = 0.0002). In conclusion, habitual cocaine use is a strong predictor of SB and was unrelated to recency of use. A potential mechanism for SB may be related to cocaine-induced desensitization of the beta-adrenergic receptor secondary to continuous exposure. Symptomatic SB was not observed; thus, pacemaker therapy was not indicated.

Stability of pacing indices and need for pacing in cardiac transplant patients over 1 year of follow-up.

BACKGROUND: A significant minority of cardiac transplant patients require permanent pacemaker (PPM) implant, primarily for sinus node dysfunction. The stability of pacing indices has not been determined in this unique patient population, and data regarding ongoing need for pacing are limited. METHODS: Pacing indices (sensing, threshold, and impedance) as well as the percentage of time patients required pacing were recorded, from 30 cardiac transplant patients that underwent PPM implant, over 1 year of follow-up. Repeated measure ANOVA (analysis of variance) was used to compare pacing indices and the percentage of time patients required pacing in each cardiac chamber (right atrium (RA) and right ventricle (RV)) and at different time points. RESULTS: There was no difference in sensing among the follow-up time points (p = 0.9). Thresholds at 3 months were significantly higher compared to the day of implant (p = 0.005) and the day after implant (p = 0.03). Impedances at implant were significantly higher compared to day 1 (p < 0.001), 3 months (p < 0.003), and 12 months (p < 0.001) post-implant. The mean percentage of RA pacing was 85 ± 6% the day after implant, 74 ± 6% at 3 months, and 80 ± 6% at 1 year (p = 0.17). CONCLUSION: In cardiac transplant patients, pacing impedances decrease and thresholds trend up in short-term follow-up, but subsequent sensing, threshold, and impedance remain stable at 1 year. This is comparable to the pattern observed among noncardiac transplant PPM recipients. The atrial pacing percentage was stable over 1 year, suggesting continued relative sinus node dysfunction.

Development of the cardiac pacemaker.

The sinoatrial node (SAN) is the dominant pacemaker of the heart. Abnormalities in SAN formation and function can cause sinus arrhythmia, including sick sinus syndrome and sudden death. A better understanding of genes and signaling pathways that regulate SAN development and function is essential to develop more effective treatment to sinus arrhythmia, including biological pacemakers. In this review, we briefly summarize the key processes of SAN morphogenesis during development, and focus on the transcriptional network that drives SAN development.

High-fat diet increases vulnerability to atrial arrhythmia by conduction disturbance via miR-27b.

BACKGROUND: Lifestyle-related diseases, such as obesity and dyslipidemia are important risk factors for atrial fibrillation (AF). However, the underlying mechanism linking these diseases and AF has not been fully investigated. METHODS: Adult male mice were fed a high-fat diet (HFD) or vehicle (NC) for 2 months. Electrocardiography and in vivo electrophysiological study were performed. Mice were then sacrificed for quantification of mRNA, microRNA, and protein in atria, in addition to histological analysis. Conduction velocity (CV) in right atrium was measured by optical mapping in Langendorff perfused hearts. Cultured atrial cardiomyocytes were treated with palmitate with or without a specific microRNA inhibitor. Twelve hours after stimulation, cells were lysed, and subjected to analysis with qPCR and Western blotting. RESULTS: HFD mice showed prolonged P wave duration, increased inducibility of sustained atrial tachycardia, and reduced atrial CV than NC mice. HFD mice also showed increased expression in inflammatory cytokines, whereas fibrotic area and signals relating fibrosis were not changed. HFD mice demonstrated reduced expression of Cx40 in mRNA and protein levels, and its lateralized expression in atria. MicroRNA array analysis revealed that miR-27b expression was up-regulated in HFD mice, and luciferase assay confirmed the direct interaction between miR-27b and Cx40 3'UTR. In palmitate-stimulated atrial cardiomyocytes, miR-27b up-regulation and Cx40 down-regulation were observed, while expression of inflammatory cytokines was not altered. Inhibition of miR-27b with antisense oligonucleotides reversed the alteration caused by palmitate stimulation. CONCLUSION: HFD may increase the vulnerability to atrial arrhythmia by down-regulation of Cx40 via miR-27b, rather than fibrosis, which is independent of inflammation.

A low fibrillatory wave amplitude predicts sinus node dysfunction after catheter ablation in patients with persistent atrial fibrillation.

BACKGROUND: Concealed sinus node dysfunction (SND) may become manifest after restoration of sinus rhythm by ablation in patients with persistent atrial fibrillation (AF). The purpose of this study was to investigate the predictors of SND after catheter ablation of persistent AF. METHODS: Two hundred two consecutive patients who underwent ablation for persistent AF were enrolled. Ipsilateral pulmonary vein isolation followed by, if necessary, electrical cardioversion were performed in all patients. SND was defined when temporary and/or permanent pacemakers were needed due to sinus bradycardia after ablation. RESULTS: SND developed in 12 (5.9 %) patients. There was no difference between the patients with and without SND in terms of the age (with SND, 67 ± 9 and without, 66 ± 10 years old, P = 0.599) and sex (male; 58 vs. 79 %, P = 0.186). However, the patients with SND had a lower amplitude of the fibrillatory waves (0.115 ± 0.086 vs. 0.176 ± 0.077 mV, P = 0.009) and larger left atrial volume index (LAVI; 66 ± 31 vs. 34 ± 13, P = 0.007) than those without. A receiver operating characteristic curve identified a fibrillatory wave amplitude of 0.145 mV (AUC = 0.742; sensitivity = 65 %; specificity = 83 %) and LAVI of 47.5 ml/m(2) (AUC = 0.837; sensitivity = 82 %; specificity = 87 %) as the optimal cutoff values for predicting SND. A multivariate analysis revealed that the amplitude of the fibrillatory waves (odds ratio = 0.84 for 0.010 mV increase, 95 % CI = 0.71-0.98, P = 0.031) and LAVI (odds ratio = 1.08 for 1.0 cm(3)/m(2) increase, 95 % CI = 1.04-1.12, P < 0.001) were independent risk factors for SND. CONCLUSIONS: A low amplitude of the fibrillatory waves and a large LAVI were predictors of SND after restoration of sinus rhythm by ablation in patients with persistent AF.

Noncompaction cardiomyopathy: a substrate for a thromboembolic event.

BACKGROUND: Noncompaction cardiomyopathy (NCC) is a rare genetic cardiomyopathy characterized by a thin, compacted epicardial layer and an extensive noncompacted endocardial layer. The clinical manifestations of this disease include ventricular arrhythmia, heart failure, and systemic thromboembolism. CASE PRESENTATION: A 43-year-old male was anticoagulated by pulmonary thromboembolism for 1 year when he developed progressive dyspnea. Cardiovascular magnetic resonance imaging showed severe biventricular trabeculation with an ejection fraction of 15%, ratio of maximum noncompacted/compacted diastolic myocardial thickness of 3.2 and the presence of exuberant biventricular apical thrombus. CONCLUSION: Still under discussion is the issue of which patients and when they should be anticoagulated. It is generally recommended to those presenting ventricular systolic dysfunction, antecedent of systemic embolism, presence of cardiac thrombus and atrial fibrillation. In clinical practice the patients with NCC and ventricular dysfunction have been given oral anticoagulation, although there are no clinical trials showing the real safety and benefit of this treatment.

Permanent sinus dysfunction after pulmonary vein isolation ablation: observations and potential mechanisms.

Although transient sinus arrest has been reported during pulmonary vein isolation (PVI), the long-term impairment of sinus node after PVI has not been described. In this report, we present a case of sinus node dysfunction necessitating a permanent pacemaker, caused during PVI. Clinical data, intracardiac electrograms, and cardiac imaging were incompatible with previous sinus node dysfunction, sinus node artery occlusion, or an ectopic atrial rhythm from the pulmonary veins. Impairment of the neural pathways connecting the ganglionated plexi of the right superior pulmonary veins with the sinus node is a possible underlying mechanism.

Permanent epicardial pacing lead implantation for scheduled multistage operations in Fontan candidate.

The use of an epicardial pacing lead may be essential in pediatric patients with rhythm disturbances. In patients with single-ventricle physiology who need scheduled multistage operations, the lead could be an obstacle because of the induction of tight adhesions and the need for dissection in the next operation. We propose a novel reproducible technique for the placement of an epicardial pacing lead followed by easy dissection of the entire length of the lead in the next operation in neonates or young infants who need multistage operations.

Cerebrovascular accident under anesthesia during dental surgery.

Stroke, or cerebrovascular accident (CVA), is a medical emergency that may lead to permanent neurological damage, complications, and death. The rapid loss of brain function due to disruption of the blood supply to the brain is caused by blockage (thrombosis, arterial embolism) or hemorrhage. The incidence of CVA during anesthesia for noncardiac nonvascular surgery is as high as 1% depending on risk factors. Comprehensive preoperative assessment and good perioperative management may prevent a CVA. However, should an ischemic event occur, appropriate and rapid management is necessary to minimize the deleterious effects caused to the patient. This case report describes a patient who had an ischemic CVA while under general anesthesia for dental alveolar surgery and discusses the anesthesia management.

Latino children's body mass index at 2-3.5 years predicts sympathetic nervous system activity at 5 years.

BACKGROUND: To understand whether the relationship between young children's autonomic nervous system (ANS) responses predicted their BMI, or vice versa, the association between standardized BMI (zBMI) at 2, 3.5, and 5 years of age and ANS reactivity at 3.5-5 years of age, and whether zBMI predicts later ANS reactivity or whether early ANS reactivity predicts later zBMI, was studied. METHODS: Low-income, primarily Latino children (n=112) were part of a larger cohort study of mothers recruited during early pregnancy. Study measures included maternal prenatal weight, children's health behaviors (i.e., time watching television, fast food consumption, and time playing outdoors), children's height and weight at 2, 3.5, and 5 years, and children's ANS reactivity at 3.5 and 5 years. ANS measures of sympathetic nervous system (i.e., pre-ejection period) and parasympathetic nervous system (i.e., respiratory sinus arrhythmia) activity were monitored during rest and four challenges. Reactivity was calculated as the difference between mean challenge response and rest. Structural equation models analyzed the relationship between children's zBMI at 2, 3.5, and 5 years and ANS reactivity at 3.5 and 5 years, adjusting for mother's BMI, children's behaviors, and changes in height. RESULTS: There was no association between zBMI and ANS cross-sectionally. Children with high zBMI at 2 or 3.5 years or large zBMI increases from 2 to 3.5 years of age had decreased sympathetic activity at 5 years. Neither sympathetic nor parasympathetic reactivity at 3.5 years predicted later zBMI. CONCLUSIONS: Increased zBMI early in childhood may dampen young children's SNS responses later in life.

Asymptomatic sinus bradycardia following bariatric surgery.

Approximately 121,000 bariatric surgical procedures are performed annually, and salutary effects include a reduction in cardiovascular morbidity and mortality, risk factor modification, and improvement in sympathovagal tone. There are anecdotal accounts of unexplained sinus bradycardia (SB) after significant weight loss but no systematic studies have been conducted. The purpose of this study was to determine the frequency of incident SB, its timing, and association with weight loss, clinical characteristics, and predictors. We evaluated various clinical characteristics including resting heart rate, blood pressure, body mass index (BMI), heart rate reserve (HRR), basal metabolic rate, and exercise regimen in 151 consecutive patients who underwent bariatric surgery. Multiple logistic regression analysis was performed to determine predictors of SB. Twenty-five of 137 patients (18%) experienced postoperative SB. Patients with SB had significantly greater reduction in BMI than those without bradycardia (35 ± 9.6% and 25.7 ± 13%, respectively, p = 0.002). HRR was significantly greater in patients with SB (116 ± 14 beats/min) compared with those without bradycardia (105 ± 14 beats/min, p = 0.007). Multiple logistic regression analysis revealed that the odds of developing SB were 1.96 and 1.91 and associated with the percent decrease in BMI (95% confidence interval 1.3 to 3.0, p = 0.002) or increase in HRR (95% confidence interval 1.28 to 2.85, p = 0.002), respectively. In conclusion, SB occurred 14 ± 11 months postoperatively and its predictors were the percent reduction in BMI or increase in HRR.

Autonomic dysfunction in different subtypes of post-acute ischemic stroke.

OBJECTIVES: Central autonomic impairment is frequent in ischemic stroke at acute or chronic stages. The mechanism by which these symptoms occur in patients with ischemic stroke has not been elucidated. This study sought to investigate cardiovascular autonomic function in patients with different subtypes of post-acute ischemic stroke. METHODS: 77 ischemic stroke patients [50 patients with large-artery atherosclerosis (LAA) and 27 patients with small-vessel occlusion (SVO), average 6 months after stroke onset] and 37 elderly controls were recruited. All performed Ewing's battery autonomic function tests and power spectral analysis of heart rate variability (HRV). RESULTS: Stroke patients with both LAA and SVO had significantly lower low frequency power spectral density than controls. The prevalence of autonomic dysfunction in both groups (82.0% patients with LAA and 63.0% with SVO) was higher than that in controls (21.6%). Patients with LAA showed impairment of all parasympathetic tests (all P<0.05) and one of the sympathetic tests (mean fall in systolic blood pressure on standing: P = 0.058) and those with SVO only showed impairment in two parasympathetic tests (heart rate response to deep breathing: P = 0.010; heart rate response to standing: P = 0.004) in comparison with controls. Patients with LAA had significantly more impairment than those with SVO in some autonomic parameters (Valsalva ratio: P = 0.039; mean fall in systolic blood pressure on standing: P = 0.015). CONCLUSIONS: Irrespective of the subtype of the ischemia, post-acute stroke patients showed a parasympathetic cardiac deficit. Additionally, parasympathetic and sympathetic cardiovascular modulations were more severely impaired in patients with LAA.

Combinations of resting RSA and RSA reactivity impact maladaptive mood repair and depression symptoms.

We examined whether the combined indices of respiratory sinus arrhythmia at rest (resting RSA) and in response to a sad film (RSA reactivity) predict effective and ineffective responses to reduce sadness (adaptive vs. maladaptive mood repair) in women with histories of juvenile-onset depression (n=74) and no history of major mental disorders (n=75). Structural equation models were used to estimate latent resting RSA, depression, and adaptive and maladaptive mood repair and to test the study hypotheses. Results indicated that combinations of resting RSA+RSA reactivity (RSA patterns) predicted maladaptive mood repair, which in turn, mediated the effects of RSA pattern on depression. Further, RSA patterns moderated the depressogenic effects of maladaptive mood repair. RSA patterns were unrelated to adaptive mood repair. Our findings suggest that mood repair is one mechanism through which physiological vulnerabilities adversely affect mental health.

Atypical autonomic regulation, auditory processing, and affect recognition in women with HIV.

This study examined the effect of HIV on visceromotor (i.e., heart rate and heart rate variability) and somatomotor (i.e., auditory processing and affect recognition) components of a Social Engagement System defined by the Polyvagal Theory (Porges, 1995) that links vagal regulation of the heart with brainstem regulation of the striated muscles of the face and head. Relative to at risk HIV-seronegative women, HIV-seropositive women had less heart rate variability (i.e., respiratory sinus arrhythmia) and had poorer performance on auditory processing and affect recognition tasks. CD4 was negatively correlated with the accuracy to detect specific emotions. The observed indices of atypical autonomic and behavioral regulation may contribute to greater difficulties in social behavior and social communication between HIV-infected women and other individuals in their social network.

Cardiovascular impairment in a patient with acute myelitis.

STUDY DESIGN: Case report. OBJECTIVE: to report and discuss the development of sudden symptomatic sinus bradycardia in a 35-year-old woman with acute myelitis. CASE REPORT: A 35-year-old woman presented rapidly progressive weakness and hypoesthesia in the left hemibody. Five days after symptom onset, she developed symptomatic sinus bradycardia up to 30 b.p.m. Bradycardia was completely resolved ∼36 h after its onset. RESULTS: Cervical spine magnetic resonance imaging showed a focal T2-hyperintense intramedullary lesion at C2 level, with moderate cord swelling. The lesion involved bilaterally dorsal funiculi, and left lateral and ventral funiculi. Cardiac I-123 metaiodobenzylguanidine (MIBG) scintigraphy showed a decreased cardiac MIBG uptake suggesting sympathetic denervation. CONCLUSION: The most likely explanation for bradycardia in our patient is the myelitis-related disruption of descending vasomotor pathways, resulting in sympathetic hypoactivity. Our case extends the spectrum of the clinical presentations of cervical myelitis and emphasizes the importance of careful cardiac monitoring in acute phase of cervical myelitis.

Poverty, problem behavior, and promise: differential susceptibility among infants reared in poverty.

Do infants reared in poverty exhibit certain physiological traits that make them susceptible to the positive and negative features of their caregiving environment? Guided by theories of differential susceptibility and biological sensitivity to context, we evaluated whether high baseline respiratory sinus arrhythmia (RSA) operates as a susceptibility factor among infants reared in poverty (N = 73). Baseline RSA at 5 months, the quality of the attachment relationship at 17 months, and the interaction of these two factors were included in our models as predictors of problem behavior at 17 months. Consistent with theory, results showed no significant differences in problem behavior among infants with low baseline RSA; however, infants with high baseline RSA exhibited the lowest levels of problem behavior if reared in an environment that fostered security, and they exhibited the highest levels of problem behavior if reared in an environment that fostered disorganization. These results have important implications for the psychological health of infants living in poverty.