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.

Point process time-frequency analysis of dynamic respiratory patterns during meditation practice.

Respiratory sinus arrhythmia (RSA) is largely mediated by the autonomic nervous system through its modulating influence on the heart beats. We propose a robust algorithm for quantifying instantaneous RSA as applied to heart beat intervals and respiratory recordings under dynamic breathing patterns. The blood volume pressure-derived heart beat series (pulse intervals, PIs) are modeled as an inverse Gaussian point process, with the instantaneous mean PI modeled as a bivariate regression incorporating both past PIs and respiration values observed at the beats. A point process maximum likelihood algorithm is used to estimate the model parameters, and instantaneous RSA is estimated via a frequency domain transfer function evaluated at instantaneous respiratory frequency where high coherence between respiration and PIs is observed. The model is statistically validated using Kolmogorov-Smirnov goodness-of-fit analysis, as well as independence tests. The algorithm is applied to subjects engaged in meditative practice, with distinctive dynamics in the respiration patterns elicited as a result. The presented analysis confirms the ability of the algorithm to track important changes in cardiorespiratory interactions elicited during meditation, otherwise not evidenced in control resting states, reporting statistically significant increase in RSA gain as measured by our paradigm.

Dark-enhanced startle responses and heart rate variability in a traumatized civilian sample: putative sex-specific correlates of posttraumatic stress disorder.

OBJECTIVE: Trauma is associated with increased risk for anxiety disorders such as posttraumatic stress disorder (PTSD). To further understand biologic mechanisms of PTSD, we examined the dark-enhanced startle response, a psychophysiological correlate of anxiety, and heart rate variability (HRV) in traumatized individuals with and without PTSD. The associations of these measures with PTSD may be sex-specific because of their associations with the bed nucleus of the stria terminalis, a sexually dimorphic brain structure in the limbic system that is approximately 2.5 times larger in men than in women. METHODS: The study sample (N = 141) was recruited from a highly traumatized civilian population seeking treatment at Grady Memorial Hospital in Atlanta, Georgia. Psychophysiological responses during a dark-enhanced startle paradigm task included startle magnitude, assessed by eyeblink reflex, and measures of high-frequency HRV, during light and dark phases of the startle session. RESULTS: The startle magnitude was higher during the dark phase than the light phase (mean ± standard error = 98.61 ± 10.68 versus 73.93 ± 8.21 µV, p < .001). PTSD was associated with a greater degree of dark-enhanced startle in women (p = .03) but not in men (p = .38, p interaction = .48). Although HRV measures did not differ between phases, high-frequency HRV was greater in men with PTSD compared with men without PTSD (p = .02). CONCLUSIONS: This study demonstrates that the dark-enhanced paradigm provides novel insights into the psychophysiological responses associated with PTSD in traumatized civilian sample. Sex differences in altered parasympathetic and sympathetic function during anxiety regulation tasks may provide further insight into the neurobiological mechanisms of PTSD.

Differential structural remodeling of the left-atrial posterior wall in patients affected by mitral regurgitation with or without persistent atrial fibrillation: a morphological and molecular study.

INTRODUCTION: Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex disease where multiple factors may induce left-atrial structural remodeling (SR). We explored the differential SR of the left-atrial posterior wall (LAPW) of patients affected by MR with or without persistent AF, and the expression of key proteins involved in its pathogenesis. METHODS AND RESULTS: Light microscopy of LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and capillary density; RT-PCR and Western blotting were used to assess the mRNA and protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1 had more myocytolytic myocytes (20.8 ± 5.6% vs 14.7 ± 4.5%; P < 0.0001), increased interstitial fibrosis (10.4 ± 5.1% vs 7.5 ± 4.2%; P < 0.05), and decreased capillary density (923 ± 107 No/mm(2) vs 1,040 ± 100 No/mm(2); P < 0.0001). All of the proteins were more expressed in groups 1 and 2 than in controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were higher in group 1 than in group 2. CONCLUSIONS: The LAPW of MR patients with or without AF shows considerable SR. The former has more severe histopathological changes and higher levels of proteins involved in SR, thereby reaching a threshold beyond which the sinus impulse cannot normally activate atrial myocardium.

A novel finding of the atrial substrate properties and long-term results of catheter ablation in chronic atrial fibrillation patients with left atrial spontaneous echo contrast.

BACKGROUND: The atrial substrate in chronic atrial fibrillation (AF) patients with a left atrial spontaneous echo contrast (LASEC) has not been previously reported. The aim of this study was to investigate the atrial substrate properties and long-term follow-up results in the patients who received catheter ablation of chronic AF. METHODS: Of 36 consecutive patients with chronic AF who received a stepwise ablation approach, 18 patients with an LASEC (group I) were compared with 18 age-gender-left atrial volume matched patients without an LASEC (group II). The atrial substrate properties including the weighted peak-to-peak voltage, total activation time during sinus rhythm (SR), dominant frequency (DF), and complex fractionated electrograms (CFEs) during AF in the bi-atria were evaluated. RESULT: The left atrial weighted bipolar peak-to-peak voltage (1.0 ± 0.6 vs 1.6 ± 0.7 mV, P = 0.04), total activation time (119 ± 20 vs 103 ± 13 ms, P < 0.001) and DF (7.3 ± 1.3 vs 6.6 ± 0.7 Hz, P < 0.001) differed between group I and group II, respectively. Those parameters did not differ in the right atrium. The bi-atrial CFEs (left atrium: 89 ± 24 vs 92 ± 25, P = 0.8; right atrium: 92 ± 25 vs 102 ± 3, P = 0.9) did not differ between group I and group II, respectively. After a mean follow-up of 30 ± 13 month, there were significant differences in the antiarrhythmic drugs (1.1 ± 0.3 vs 0.7 ± 0.5, P = 0.02) needed after ablation, and recurrence as persistent AF (92% vs 50%, P = 0.03) between group I and group II, respectively. After multiple procedures, there were more group II patients that remained in SR, when compared with group I (78% vs 44%, P = 0.04). CONCLUSION: There was a poorer atrial substrate, lesser SR maintenance after catheter ablation and need for more antiarrhythmic drugs in the chronic AF patients with an LASEC when compared with those without an LASEC.

Cardiac vagal control in nonmedicated depressed women and nondepressed controls: impact of depression status, lifetime trauma history, and respiratory factors.

OBJECTIVE: To evaluate the impact of acute stress and relationship-focused imagery on cardiac vagal control, as indicated by levels of respiratory sinus arrhythmia (RSA), in depressed and nondepressed women. Impairment in cardiac parasympathetic (vagal) control may confer risk for cardiac mortality in depressed populations. METHODS: Electrocardiogram and respiratory rate were evaluated in 15 nonmedicated depressed women and 15 matched controls during two laboratory conditions: 1) a relationship-focused imagery designed to elicit vagal activation; and 2) a speech stressor designed to evoke vagal withdrawal. RESULTS: As expected, the relationship-focused imagery increased RSA (F(3,66) = 3.79, p = .02) and the speech stressor decreased RSA (F(3,66) = 4.36, p = .02) across women. Depressed women exhibited lower RSA during the relationship-focused imagery, and this effect remained after control for respiratory rate and trauma history (F(1,21) = 5.65, p = .027). Depressed women with a trauma history exhibited the lowest RSA during the stress condition (F(1,22) = 9.61, p = .05). However, after controlling for respiratory rate, Trauma History × Task Order (p = .02) but not Trauma History × Depression Group (p = .12) accounted for RSA variation during the stress condition. CONCLUSION: Depression in women is associated with lower RSA, particularly when women reflect on a close love relationship, a context expected to elicit vagal activation and hence increase RSA. In contrast, depression-related variation in stressor-evoked vagal activity seems to covary with women's trauma history. Associations between vagal activity and depression are complex and should be considered in view of the experimental conditions under which vagal control is assessed, as well as physiological and behavioral factors that may affect vagal function.

Sex differences in heart rate responses to script-driven imagery soon after trauma and risk of posttraumatic stress disorder.

OBJECTIVE: To investigate in trauma survivors the predictive validity of heightened physiological responsivity to script-driven imagery for the development of posttraumatic stress disorder (PTSD) and to evaluate the interactive effect of survivors' sex. Physiological responses to idiosyncratic trauma reminders may be predictive of later PTSD. The majority of previous studies have been cross sectional and have produced mixed findings. Sex differences may contribute to this heterogeneity. METHODS: Heart rate (HR) and respiratory sinus arrhythmia were measured at 2 weeks post trauma in 158 assault survivors during baseline and as they listened to an idiosyncratic trauma script. At 6 months, 15.2% of male and 28.1% of female participants met the diagnostic criteria for PTSD. RESULTS: Generalized linear model and logistic regression analyses showed that HR response to script-driven imagery and sex interacted in predicting PTSD symptom severity at 6 months. Women had greater PTSD symptom severities overall. Female HR responders to script-driven imagery showed the highest PTSD symptom severities and were almost three times more likely to develop PTSD at 6 months compared with men and female nonresponders (odds ratio, 2.72; 95% confidence interval, 1.13-6.57). Respiratory sinus arrhythmia responder type did not predict PTSD (odds ratio, 0.64; 95% confidence interval, 0.30-1.33). CONCLUSION: Female trauma survivors who respond to trauma reminders with increased HR may be at particular risk of developing PTSD. Physiological reactivity to trauma cues may be a useful index for screening and prevention of PTSD.

Effectiveness of respiratory-sinus-arrhythmia biofeedback on state-anxiety in patients undergoing coronary angiography.

AIM: This study is a report of a study conducted to evaluate the value of psychological assistance including respiratory-sinus-arrhythmia biofeedback training in its ability to reduce the level of anxiety in patients undergoing coronary angiography. BACKGROUND: Coronary angiography has been reported to cause anxiety and emotional stress. METHODS: Between March 2004 and January 2005, 212 patients undergoing routine elective coronary angiography for the evaluation of stable coronary artery disease were randomized into two groups. In the psychological support group (n = 106) a structured psychological conversation and respiratory-sinus-arrhythmia biofeedback training were offered prior to coronary angiography. In the control group (n = 106) standard care and information was provided without psychological support. State-anxiety was measured (scale 20-80) 1 day prior to and after coronary angiography, along with blood pressure and heart rate. FINDINGS: Prior to coronary angiography, state-anxiety was 54.8 +/- 11.5 (mean +/- SD) in the control group and 54.8 +/- 12.6 in the psychological support group. After coronary angiography, state-anxiety was 47.9 +/- 18.5 in the control group but 28.3 +/- 12.5 in the psychological support group (Wilcoxon rank sum test W = 7272, P < 0.001). Blood pressure was statistically significantly lower in the psychological support group prior to the intervention and the day after coronary angiography. CONCLUSION: Psychological support including respiratory-sinus-arrhythmia biofeedback is an effective and simple tool that could be used by nurses to reduce state-anxiety and emotional stress in patients undergoing coronary angiography.

Ablation of permanent AF: adjunctive strategies to pulmonary veins isolation: targeting AF NEST in sinus rhythm and CFAE in AF.

Atrial fibrillation (AF) is highly prevalent and accounts for significant morbidity, mortality, and health care costs. Catheter ablation has become a therapeutic option in the management of this challenging arrhythmia. To optimize procedure safety and long-term efficacy, innovative technologies and ablation strategies have been targeting either the triggers initiating AF or the substrate responsible for its maintenance. Pulmonary vein (PV) isolation, initially limited to the PVs, has been modified to encompass the left atrial myocardium surrounding the PV ostia, namely the LA-PV antra. Our current intracardiac echo-guided approach to PV antra isolation, including the adjunct of superior vena cava isolation, has likely accounted for higher success rates by electrically isolating further AF trigger sites, modifying the substrate for AF maintenance and possibly by modulating a dysfunctional autonomic cardiac nervous system. However, the long-term outcome following ablation of permanent AF can be further improved by incorporating adjunctive ablation strategies to PV isolation, such as targeting ablation at sites exhibiting complex atrial fractionated electrograms (CFAEs)during AF or at sites exhibiting the so-called AF nests during real-time spectral mapping in sinus rhythm.

Efficacy and late recurrences with wide electrical pulmonary vein isolation for persistent and permanent atrial fibrillation.

AIMS: Early recurrences of atrial arrhythmia after wide electrically isolating ablation for atrial fibrillation (AF) are well described, but the long-term risk of recurrence for patients with persistent and permanent AF has not been studied in detail. METHODS AND RESULTS Fifty-six consecutive patients [45 men (80.4%), age 55.9 +/- 8.7 years] with persistent [39(69.6%)] or permanent [17(30.4%)] AF were followed for 21.6 +/- 8.8 months after ablation. Atrial fibrillation duration prior to ablation was 6.4 +/- 5.6 years. Electrically isolating lesions encircling the left and right pulmonary veins (PVs) in pairs were created. After 1.5 +/- 0.7 procedures, 48 (85.7%) had sinus rhythm (SR) at 21.6 +/- 8.8 months of follow-up: achieved with 1 procedure in 27 (56.3%) and without anti-arrhythmics in 30 (62.5%). Atrial fibrillation recurrence was observed in 69.6% after the first and 46.4% after the last procedure. Of those with late recurrences (>90 days) following the last procedure, most [18 (69.2%)] did not have early recurrences. Pre-procedural AF duration (P = 0.007) and female gender (P = 0.005) were independent predictors of recurrence following the last procedure. CONCLUSION: Circumferential PV isolation is effective in most patients with persistent or permanent AF. However, repeat procedures are frequently required. Late recurrences are common and not precluded by the absence of early post-procedural arrhythmias.

Cardiac vagal control in the severity and course of depression: the importance of symptomatic heterogeneity.

BACKGROUND: Impaired cardiac vagal control (CVC), as indexed by respiratory sinus arrhythmia, has been investigated as a risk factor for major depressive disorder (MDD), but prior findings are mixed with respect to whether impaired CVC predicts greater global depression severity and/or a more severe course of disorder. One possible explanation for mixed findings is that CVC abnormalities in MDD are related more closely to specific depression symptoms than to the syndrome as a whole. METHODS: Depression severity (both global and symptom-specific indices) and electrocardiogram measures of resting CVC were obtained from 151 diagnosed MDD participants at intake, before randomization to a novel treatment for depression (acupuncture), and again after 8 and 16 weeks. RESULTS: Resting CVC did not predict global indices of depression in cross-sectional or longitudinal analyses. In symptom-specific analyses, resting CVC was positively related to sad mood and crying and inversely related to middle and late insomnia. Improvement in late insomnia was related to increases in CVC over time. LIMITATIONS: Relationships between CVC and MDD were studied only within the clinical range of severity. Symptom analyses were exploratory and hence did not correct for Type I error. CONCLUSIONS: Resting CVC did not exhibit concurrent or prospective relations with overall depression severity but a few specific symptoms did. Symptomatic heterogeneity across samples may account for mixed findings within the CVC-depression literature.

Implementation and interpretation of respiratory sinus arrhythmia measures in psychosomatic medicine: practice against better evidence?

Respiratory sinus arrhythmia (RSA) or high-frequency heart rate variability has been widely used as a noninvasive measure of cardiac vagal tone. However, their dependency on both respiration rate and tidal volume is largely ignored. Only a minority of studies published in Psychosomatic Medicine in recent years has implemented precautions for controlling respiration rate in RSA measures, and tidal volume effects were only rarely addressed. We discuss methodologic issues related to respiratory control methods and present data that demonstrate that both respiration rate and tidal volume contribute substantially to the within-individual RSA variance under conditions of variable breathing, with tidal volume contributing up to one third beyond respiration rate. Finally, we outline a respiratory control method for the time-domain index of RSA and review research pertaining to its reliability, validity, and experimental application.

Role of the low amplitude potential in the initial P wave signal-averaged electrocardiogram [corrected] in sick sinus syndrome.

BACKGROUND: The cause of abnormally low amplitude of the initial P wave signal-averaged electrocardiogram (P-SAECG) in patients with sick sinus syndrome (SSS) is unknown. METHODS AND RESULTS: Thirteen normal patients (Group C) and 33 with SSS (Group S) were examined. The root mean square amplitude for the initial 30 ms (EP30) and the duration of below-4 microV signals of the filtered P waves (ED4) were measured using the P-SAECG. The interval from an atrial potential on the sinus-node electrogram (SNE) to P wave onset (AS-P), and the interval from the P wave to the atrial potential on the His-bundle-electrogram (P-AH) were measured in the electrophysiological study. The sino-atrial conduction time was measured by a conventional method (indirect sino-atrial conduction time (SACTi)) and using SNE (direct sino-atrial conduction time (SACTd)). The EP30 was significantly lower and the ED4 significantly longer in Group S. The AS-P was significantly longer in Group S (p<0.01), but the P-AH was not different. In Group S, the AS-P was significantly correlated with EP30 and ED4 (p<0.01), but the P-AH was uncorrelated. The SACTi was significantly correlated with EP30 and ED4 (p<0.05), but the SACTd was uncorrelated. CONCLUSION: The abnormality of the initial portion of the P-SAECG observed in SSS appears to be due to disturbed conduction through the atrial myocardium around the sino-atrial node.

Sinus rhythm electrogram shape measurements are predictive of the origins and characteristics of multiple reentrant ventricular tachycardia morphologies.

INTRODUCTION: During clinical electrophysiologic study, multiple clinical tachycardia morphologies often can be induced in the infarct border zone, and all morphologies must be targeted for ablation therapy to be successful. Analysis of sinus rhythm electrogram shape for localizing figure-of-eight reentrant circuits in cases of multiple morphologies is proposed. METHODS AND RESULTS: Sinus rhythm activation maps were constructed from bipolar electrograms acquired at 196 to 312 sites in the epicardial border zone in 10 postinfarction canine hearts. In each heart, at least two distinct figure-of-eight reentrant ventricular tachycardia morphologies were inducible by premature electrical stimulation, as determined by activation maps of sustained tachycardias. Sinus rhythm maps were used to predict the location of the isthmus (central common pathway [CCP]), which is the protected region of the circuit bounded by arcs of block (mean accuracy 76.7 +/- 4%). Although reentrant circuits differed, the positions of the entrance point of each CCP were common. The location of the line that would span the CCP at its narrowest width also was estimated (mean accuracy 91.3 +/- 5%). Ablation at this line is expected to prevent reentry recurrence. In one test experiment, ablation prevented recurrence of both sustained reentrant tachycardia morphologies. CONCLUSION: Sinus rhythm electrogram analyses are useful for (1) localizing multiple reentrant circuits with differences in morphology that are inducible by premature stimulation in the infarct border zone, and (2) locating and orienting the position of a linear lesion for preventing recurrence of all morphologies with minimal damage to the heart.

Bradiarritmias / Bradyarrythmia

Considera-se bradirritmia uma fequência cardíaca menor que 50 bpm. Evidentemente, esse conceito é relativo à situação metabólica e à idade do paciente, mesmo porque uma frequência cardíaca de 45bpm ou menos pode ser normal durante o sono em pacientes idosos, assim como uma frequência de 70 bpm constituti bradicardia em recém-nascidos ou em pacientes com febre. Isso demonstra que o diagnóstico depende do quadro clínico do paciente.

Acute moderate alcohol consumption affects cardiovascular responses in healthy males with different tolerance levels.

We investigated the effect of acute moderate alcohol consumption or placebo on respiratory sinus arrhythmia (RSA) in 48 healthy participants with different levels of alcohol tolerance but no abuse. In the electrocardiogram recording, auditory stimuli were presented at defined points in the respiratory cycle, which allows a non-invasive measure of CNS control over RSA. After alcohol consumption we found a decrease in RSA with auditory stimulation. Moreover, individuals with low tolerance showed only a slight change in the RSA after alcohol intake compared to baseline, whereas the placebo drink led to a reduced RSA. In subjects with high alcohol tolerance, alcohol consumption led to a reduction of RSA, with no change after placebo. These results suggest a centrally driven influence on RSA that is changed by alcohol ingestion depending upon subjects' levels of alcohol tolerance.

Deficits of respiratory-cardiac coupling in heavy drinkers.

1. Physiological evidence of chronic alcohol abuse prior to the onset of clinical signs of alcohol dependence is difficult to obtain The purpose of this study was to search for possible non-invasive indicators for chronic alcohol consumption yielding information in addition to conventional biological markers. 2. The authors investigated the relationship between respiratory-cardiac coupling and blood alcohol concentration (BAC) in male subjects who lost their driver's license from drunk driving. 3. We found that subjects who had a high BAC level (0.16-0.31% at the time of offense) show altered respiratory sinus arrhythmia (RSA) and, in particular, an altered heart-rate response to auditory stimulation and compared them to a control group of social drinkers. Normal subjects showed a pronounced acoustic heart-rate response, i.e., particularly during expiration there was a difference between the interbeat-interval (IBI) traces with and without auditory stimulation. Subjects who had lost their driver's license from drunk driving had an overall severely reduced heart-rate response, that was even absent particularly in the subgroup having high BAC values (0.21-0.31%). The authors also found some evidence that in the latter subgroup IBI, RSA, and acoustic heart-rate responses partially recover after a six-month period of abstinence. 4. Specific parameters of the acoustic heart-rate response are changed in our group of alcohol abusers presumably, due to impairment of vagal function. These parameters may therefore be useful to serve as a non-invasive measure of alcohol abuse.

Autonomic and EEG patterns distinguish transcending from other experiences during Transcendental Meditation practice.

This study compared EEG and autonomic patterns during transcending to "other" experiences during Transcendental Meditation (TM) practice. To correlate specific meditation experiences with physiological measures, the experimenter rang a bell three times during the TM session. Subjects categorized their experiences around each bell ring. Transcending, in comparison to "other" experiences during TM practice, was marked by: (1) significantly lower breath rates; (2) higher respiratory sinus arrhythmia amplitudes; (3) higher EEG alpha amplitude; and (4) higher alpha coherence. In addition, skin conductance responses to the experimenter-initiated bell rings were larger during transcending. These findings suggest that monitoring patterns of physiological variables may index dynamically changing inner experiences during meditation practice. This could allow a more precise investigation into the nature of meditation experiences and a more accurate comparison of meditation states with other eyes-closed conditions.