Towards Automated Quantification of Atrial Fibrosis in Images from Catheterized Fiber-Optics Confocal Microscopy Using Convolutional Neural Networks.

Clinical approaches for quantification of atrial fibrosis are currently based on digital image processing of magnetic resonance images. Here, we introduce and evaluate a comprehensive framework based on convolutional neural networks for quantifying atrial fibrosis from images acquired with catheterized fiber-optics confocal microscopy (FCM). FCM images in three regions of the atria were acquired in the beating heart in situ in an established transgenic animal model of atrial fibrosis. Fibrosis in the imaged regions was histologically assessed in excised tissue. FCM images and their corresponding histologically-assessed fibrosis levels were used for training of a convolutional neural network. We evaluated the utility and performance of the convolutional neural networks by varying parameters including image dimension and training batch size. In general, we observed that the root-mean square error (RMSE) of the predicted fibrosis was decreased with increasing image dimension. We achieved a RMSE of 2.6% and a Pearson correlation coefficient of 0.953 when applying a network trained on images with a dimension of 400 × 400 pixels and a batch size of 128 to our test image set. The findings indicate feasibility of our approach for fibrosis quantification from images acquired with catheterized FCM using convolutional neural networks. We suggest that the developed framework will facilitate translation of catheterized FCM into a clinical approach that complements current approaches for quantification of atrial fibrosis.

Evidence for a Heritable Contribution to Atrial Fibrillation Associated With Fibrosis.

OBJECTIVES: The aim of this study was to define the population-based familial clustering of atrial fibrillation (AF) that is associated with fibrosis and describe evidence for a heritable predisposition. BACKGROUND: Although a heritable contribution to AF is well-established and the association of fibrosis with AF is well-recognized, no studies have analyzed the genetic contribution to AF co-occurring with fibrosis. METHODS: AF patients with magnetic resonance imaging-confirmed fibrosis were identified in a population-based health sciences center database linked to a Utah genealogy. Familial clustering of AF/fibrosis was defined by analysis of pairwise case relatedness, estimation of relative risk of AF/fibrosis in relatives, and identification of high-risk AF/fibrosis pedigrees. RESULTS: The 694 individuals identified with AF/fibrosis who had at least 3 generations of genealogy data were found to have significantly elevated pairwise relatedness (p < 0.001), even when first- and second-degree relationships were ignored (p < 0.001). Significantly elevated risks for AF/fibrosis among first- (relative risk [RR]: 4.65), second- (RR: 3.14), and third-degree (RR: 2.70) relatives of individuals with AF/fibrosis were observed. We identified 157 extended Utah pedigrees with a significant excess of AF/fibrosis among descendants. CONCLUSIONS: There is a strong heritable contribution to predisposition to AF co-occurring with fibrosis. We suggest that this study provides a unique foundation for a search for predisposition genes, specifically for AF co-occurring with fibrosis.

Clinical Characteristics and Outcome of Patients with Situational Syncope Compared to Patients with Vasovagal Syncope.

BACKGROUNDS: The purpose of the study was to assess the clinical outcome of patients with situational syncope (SS) compared to patients with vasovagal syncope (VVS). METHODS: We assessed the prevalence, patients' characteristics, and outcome of consecutive patients with SS and VVS who presented to the Faint and Fall Clinic (University of Wisconsin) between January 2013 and December 2015. RESULTS: SS was found in 55/1,401 (4.0%) syncope patients with follow-up data available in 47 patients: defecation (n = 16), micturition (n = 15), cough (n = 10), swallow (n = 3), laughter (n = 1), sneeze (n = 1), and cough plus laughter (n = 1). Over the same time period, 252/1,401 patients (18%) were diagnosed with VVS with follow-up data available in 171 patients. Compared with VVS patients, SS patients were older, more likely to be male, had a higher prevalence of hypertension, had an absence of prodromes, and experienced more injuries at the time of syncope (P = 0.01 for all). During a mean follow-up duration of 15.4 ± 9.1 months, syncope recurred in 5/47 (10.6%) patients with SS and 16/171 (9.4%) patients with VVS. The recurrence rates at 1 year and 2 years were 20% (95% SE ± 13) and 40% (95% SE ± 20) for the SS group, and 23% (95% SE ± 13) and 43% (95% SE ± 20) for the VVS group (P = 0.6). No patient died. CONCLUSIONS: We have shown in a large cohort of consecutive patients with syncope that SS is a relatively infrequent form of reflex syncope with different clinical characteristics but similar recurrence rate to VVS.

The pathophysiologic mechanisms associated with hypotensive susceptibility.

INTRODUCTION: Patients with vasovagal syncope (VVS) and positive tilt table test (TTT) were not found to benefit from pacing in the ISSUE-3 trial despite the presence of spontaneous asystole during monitoring. "Hypotensive susceptibility" unmasked by TTT was reported as a possible explanation. The purpose of this study was to assess the pathophysiologic mechanisms associated with hypotensive susceptibility. METHODS: 366 consecutive patients with the diagnosis of VVS who also had TTT were identified. Baroreflex gain (BRG) in addition to blood pressure (BP) and heart rate (HR) responses during the first 20 min of TTT were analyzed and compared between patients with positive TTT (n = 275, 75 %) and negative TTT (n = 91, 25 %). RESULTS: The mean BRG was similar between the groups (12.5 ± 6.3 versus 12.4 ± 6.3 ms/mmHg, p = 0.72); however, an age-dependent decrease was noted (17.6 ± 4.8, 15.0 ± 6.0, 10.6 ± 4.2, 10.3 ± 6.4 and 9.9 ± 8.5 ms/mmHg for patients <21, 21-40, 41-60, 61-80 and >80 years old, respectively; p < 0.001). In addition, we saw a main effect of age on the type of response with a greater prevalence of a vasodepressor response in older subjects (p < 0.001). During the first 20 min of TTT, BP was similar in patients with tilt-positive VVS when compared with patients with tilt-negative VVS; however, HR was significantly lower. CONCLUSION: BRG is similar in tilt-positive VVS patients when compared with tilt-negative VVS patients. An age-dependent decrease in BRG was noted with a higher prevalence of a vasodepressor response seen in older patients. The clinical significance of the blunted HR response in tilt-positive VVS remains to be determined.

Restoring Sinus Rhythm Improves Baroreflex Function in Patients With Persistent Atrial Fibrillation.

BACKGROUND: Studies have suggested that patients with atrial fibrillation (AF) have impairment in the baroreflex. It is not clear whether these findings are the result of the associated comorbid conditions or the arrhythmia itself. We hypothesized that AF is associated with impairment in baroreflex function and that the arrhythmia itself is a contributing factor. METHODS AND RESULTS: Twenty-four patients with persistent AF referred for cardioversion were enrolled. A second group of patients with no history of AF matched for age and left ventricular ejection fraction was identified and served as the control group. In the AF group, baroreflex gain (BRG) was measured on the day of cardioversion (Day 1) and again at 30 days post-cardioversion (Day 30) in patients who remained in sinus rhythm (SR). The clinical characteristics of patients with AF were not different than those of the control group. The mean BRG in the AF group on Day 1 was significantly lower than the mean BRG of the control group (5.2±3.6 versus 10.8±5.5 ms/mm Hg, P<0.05). Ten patients experienced AF recurrence before the 30-day follow-up and 14 patients remained in SR. In the group that remained in SR, BRG increased from 4.1±3.7 ms/mm Hg on Day 1 to 7.0±6.0 ms/mm Hg on Day 30 (P<0.01). CONCLUSION: We have shown that AF is associated with impairment of the baroreflex and that restoration of SR improves BRG. Our data suggest that AF might be a contributing factor to the observed impairment in BRG and that restoring SR might help improve baroreflex function.

The Role of the Baroreflex in Tilt Table Testing: Outcome and Type of Response.

OBJECTIVES: The purpose of this study was to better understand the role of the baroreflex in tilt-induced vasovagal syncope (VVS). BACKGROUND: The role of the baroreflex in tilt-induced VVS remains controversial. The authors hypothesized that: 1) patients with positive tilt table test (TTT) results have greater baroreflex gain (BRG) compared with patients with negative TTT results; and 2) patients with tilt-induced asystole have greater BRG compared with patients without asystole. METHODS: Using the sequence method, BRG measurements were obtained in 438 consecutive patients undergoing TTT. Two hundred sixty-eight patients (61%) had positive TTT results (mean age 50 ± 21 years; 34% men), and 170 patients (39%) had negative TTT results (mean age 48 ± 21 years; 35% men). RESULTS: Mean BRG was significantly higher in patients with positive TTT results compared with those with negative TTT results (12.9 ± 6.0 ms/mm Hg vs. 11.5 ± 6.0 ms/mm Hg; p = 0.01). Among the 268 patients with positive TTT results, 23 (9%) had more than 3 s of asystole (mean age 37 ± 17; 30% men), and 245 patients had a mixed vasodepressor or cardioinhibitory response without asystole (mean age 51 ± 17 years; 34% men). Mean BRG was greater in patients with tilt-induced asystole (>3 s) compared with patients without asystole (15.3 ± 5.9 ms/mm Hg vs. 12.7 ± 5.9 ms/mm Hg; p = 0.03). CONCLUSIONS: The results of this study demonstrate that baseline BRG was higher in patients with positive TTT results compared with those with negative TTT results, with greater values noted in patients with tilt-induced asystole (>3 s) compared with those without asystole.

Mechanisms of sinus node cycle length changes during ventricular fibrillation.

OBJECTIVE: We have previously shown that up to one-third of patients develop no change or an increase in sinus node cycle length (SNCL) during ventricular fibrillation (VF). The purpose of the present study was to investigate the mechanism of SNCL changes during VF in a swine model. We hypothesized that changes in SNCL during VF are vagally-mediated. METHODS: In 33 anesthetized pigs DC current was used to induce VF for 10 s followed by defibrillation. SNCL changes were assessed during VF and compared to baseline. Animals that had ventriculo-atrial conduction during VF were excluded. Post-defibrillation, the pigs were randomized to receive atropine, propranolol, atropine + propranolol or placebo followed by repeat VF induction and measurement of SNCL changes. RESULTS: Ventriculo-atrial conduction was present in 14 pigs prohibiting SNCL measurements. In the remaining 19 animals, 10 demonstrated SNCL shortening (S-Group) and 9 demonstrated non-shortening (NS-Group). Atropine decreased the absolute change in SNCL from 51.2 to 26.6 ms (n = 6; p = 0.03). It attenuated the SNCL shortening previously observed in the S-Group (-99.2 ms versus -47.9 ms, p = 0.04) and reversed the SNCL prolongation initially observed in the NS-Group (27.1 ms versus -6.5 ms, p = 0.13). Similarly, atropine + propranolol decreased the absolute change in SNCL from 33.3 to 12.2 ms (n = 4; p = 0.05). No significant changes were noted with propranolol or placebo. INTERPRETATION: The SNCL changes during VF appear to be vagally-mediated. The clinical implications vis-à-vis defibrillation threshold and future device programming await future studies.

"Vasovagal" response during ventricular fibrillation: incidence and implications.

BACKGROUND: The purpose of this study was to assess the relationship between changes in sinus node cycle length (SNCL) during ventricular fibrillation (VF) and the peripheral changes in blood pressure (BP) and sympathetic nerve activity (SNA) in human subjects. We hypothesized that patients with no SNCL shortening during VF have a vasovagal-like response with a greater decrease in BP and SNA when compared to patients with SNCL shortening. METHODS: SNCL, BP, and SNA recordings were attempted in 24 patients undergoing the implantation of a dual-chamber implantable defibrillator. Changes were measured during the first 5 seconds of VF and compared with the 5 seconds prior to VF induction. RESULTS: SNCL shortened during VF in nine patients (mean%∆SNCL = -12 ± 8%) and remained unchanged or lengthened in seven patients (mean%∆SNCL = 7 ± 7%). Eight patients had ventriculoatrial (VA) conduction prohibiting assessment of SNCL changes. In patients with SNCL shortening, the %∆MBP (mean BP) was -47 ± 6% compared to -58 ± 8% in patients with no SNCL shortening (P < 0.01). In patients with VA conduction, the %∆MBP was -54 ± 3%. SNA recordings were successfully obtained in four patients. When compared to baseline, SNA increased by 34 ± 30% in two patients with SNCL shortening, decreased by 25% in one patient with SNCL lengthening, and by 90% in the fourth patient with VA conduction. CONCLUSIONS: We have shown that patients with no SNCL shortening have a significantly greater decrease in MBP during VF when compared to patients with SNCL shortening. The underlying mechanism appears to be reflex mediated with a vasovagal-like response in patients with no SNCL shortening.

The effects of radio-frequency ablation on blood pressure control in patients with atrial fibrillation and hypertension.

PURPOSE: The effects of radio-frequency ablation (RFA) on blood pressure (BP) regulation in patients with atrial fibrillation (AF) and hypertension remain unknown. We hypothesized that patients with successful ablation had a lower BP and/or lesser utilization of antihypertensive drug therapy during follow-up when compared to patients with failed ablation. METHODS AND RESULTS: This was a retrospective evaluation of patients with AF and hypertension treated with ablation at the University of Utah between July 2006 and June 2010. BP and use of antihypertensive medications were assessed at baseline and 1 year follow-up. A total of 167 patients were identified. Eight patients were excluded due to the need for AAD therapy beyond the blanking period thus leaving 80 patients in the success group and 79 patients in the failure group. The mean BP and HR at baseline were not significant between the groups. In the success group, the mean systolic BP decreased from a baseline value of 129 ± 17 to 125 ± 14 mmHg at 1 year (p = 0.075). In contrast, in the failure group, the mean systolic BP increased from a baseline value of 124 ± 16 to 127 ± 14 mmHg at 1 year (p = 0.176). Between-group comparison revealed a p value of 0.026. Minimal changes in diastolic BP were noted in both groups. No significant changes in antihypertensive therapy were noted. CONCLUSION: We have shown that successful catheter ablation in patients with AF and hypertension is associated with a decrease in systolic BP when compared to an increase in patients with failed ablation. Our findings suggest that restoring sinus rhythm could have an antihypertensive effect in patients with AF and hypertension.

Atrial fibrillation: an independent risk factor for nonaccidental falls in older patients.

BACKGROUND: Nonaccidental falls are often the result of a combination of factors including cardiovascular disorders such as orthostatic hypotension and unspecified cardiac arrhythmias. The objective of this study was to determine if there is an association between atrial fibrillation (AF) and nonaccidental falls. METHODS: We reviewed the records of 442 consecutive patients >65 years old who presented to the Emergency Department at the University of Utah Medical Center with a complaint of fall. RESULTS: Two-hundred eleven patients presented with nonaccidental fall, 231 patients with accidental fall. Patients with nonaccidental fall were more likely to be older, have a history of hypertension and neurological disorders, and taking five or more medications when compared to patients with accidental fall. Despite a similar prevalence of sinus rhythm at presentation, the prevalence of a history of AF was significantly higher in patients with nonaccidental fall compared to patients with accidental fall (26% vs 15%; P = 0.003). After adjusting for clinically and statistically significant predictors with a multivariate logistic regression analysis, AF, neurological disorders, and age ≤81 years were independent predictors of nonaccidental fall. In patients ≤81 years old (median age), the risk of nonaccidental falls was 2.5 times greater in patients with a history of AF when compared to those without a history of AF (odds ratio = 2.53 [confidence interval 95% 1.3-5], P = 0.007). CONCLUSION: AF is an independent risk factor for nonaccidental falls. Our results emphasize the need to screen for AF in patients presenting with nonaccidental fall.

Restoring sinus rhythm results in blood pressure reduction in patients with persistent atrial fibrillation and a history of hypertension.

INTRODUCTION: The long-term effects of atrial fibrillation (AF) on blood pressure (BP) in patients with hypertension (HTN) remain unclear. We hypothesized that restoration of normal sinus rhythm (NSR) results in a decrease in BP despite the expected increase in cardiac output. METHODS AND RESULTS: Twenty-four-hour BP measurements were obtained during AF, and on Day 1 and Day 30 post-successful cardioversion in 18 patients with AF and HTN (cardioversion group), and another 22 patients with AF and HTN with no immediate plans for cardioversion (control group). Except for the duration of AF, the clinical characteristics and use of medications were similar between the groups. In the cardioversion group, a significant decrease in diastolic blood pressure (DBP) and mean blood pressure (MBP) were noted on Day 1 post-cardioversion with no significant change in systolic blood pressure (SBP): 117/74/88 ± 13/9/9 mmHg during AF and 116/70/85 ± 13/9/10 mmHg during Day 1 post-cardioversion (P = 0.68; <0.01 and 0.04 for SBP, DBP, and MBP, respectively). In the 13 subjects who remained in NSR at Day 30, DBP and MBP decreased further on Day 30 when compared to Day 1 with no significant change in SBP: 118/76/90 ± 13/7/8 mmHg during AF; 119/72/88 ± 12/8/9 mmHg during Day 1; and 118/69/86 ± 10/8/7 mmHg during Day 30 post-cardioversion (P = 0.97; <0.001 and 0.03 for SBP, DBP, and MBP, respectively). In the control group, no significant changes in BP were noted. CONCLUSION: Restoring NSR in patients with AF and HTN resulted in a sustained decrease in DBP and MBP. To our knowledge, this is the first study to show that maintenance of NSR improves BP control in patients with AF and HTN.

Syncope in the emergency department: comparison of standardized admission criteria with clinical practice.

AIMS: Syncope is a major health care problem that accounts for many emergency department (ED) and hospital admissions. This study was conducted to investigate the short-term risk of serious events in patients presenting to the ED with syncope and to compare guideline-based admission criteria with those adopted in clinical practice. METHODS AND RESULTS: A single-centre retrospective analysis was performed on ED visits between January and June 2009. We used the ICD-9 code 780.2 for syncope as the primary diagnosis. The prevalence of serious events within 7 days of the index presentation was evaluated. In addition, admissions and discharges were classified as being appropriate or inappropriate based on standardized guideline-based criteria integrated in a new Faint-Algorithm developed at the University of Utah. Two hundred and fifty-four ED visits met the inclusion criteria. One hundred and thirty-six patients were discharged home and the remaining 118 were admitted. The prevalence of serious events in the discharged and admission groups were 5 and 10, respectively, (P= NS). According to the Faint-Algorithm, the number of inappropriate discharges and admissions were 8 out of 136 and 69 out of 118, respectively. Using the Faint-Algorithm, only 57 patients instead of 118 patients should have been admitted resulting in a 52% reduction in admission rate. Furthermore, in the remaining 197 patients who should have been discharged, the prevalence of serious events was not significantly different than that observed in the 136 patients who were actually discharged (3% vs. 4%). CONCLUSION: There are significant numbers of inappropriate discharges and admissions in patients presenting with syncope. The standardized guideline-based criteria integrated in the new Faint-Algorithm provide promise but require further prospective evaluation.

Irregular ventricular activation results in QT prolongation and increased QT dispersion: a new insight into the mechanism of AF-induced ventricular arrhythmogenesis.

INTRODUCTION: Atrial fibrillation (AF) has been shown to be associated with increased risk of ventricular arrhythmias. We have previously shown reverse electrical remodeling of the ventricles following successful restoration of sinus rhythm in patients with persistent AF. The purpose of this study was to assess the relative role of irregular ventricular activation in mediating the previously observed changes. METHODS AND RESULTS: Twenty-two patients referred for an invasive electrophysiologic study were randomized to 30 minutes of regular or irregular atrioventricular (AV) sequential pacing at 100 beats per minute (bpm) with a programmed AV interval of 100 ms. Irregular pacing was triggered from prerecorded digital signal with a mean rate of 100 bpm, and a standard deviation of 150 ms (25% of the mean rate). In the regular pacing group, QT and QTc decreased from 448 ± 102 ms and 453 ± 105 ms to 428 ± 109 ms and 442 ± 104 ms, respectively (P < 0.001 for QT interval and P < 0.001 for QTc interval). There was no significant change in QT dispersion. In the irregular pacing group, QT and QTc increased from 477 ± 104 ms and 486 ± 78 ms to 489 ± 106 ms and 500 ± 106 ms (P < 0.01 for QT interval and P = 0.03 for QTc interval). In addition, there was a significant increase in QT dispersion from 50 ± 22 ms to 66 ± 22 ms (P = 0.001). Since the rate and pacing sites were similar between the groups, we attribute the repolarization changes in the irregular pacing group to the irregular activation of the ventricles. CONCLUSION: The detrimental effects of irregular pacing go beyond the hemodynamic changes and include electrical remodeling that favors an arrhythmogenic substrate.

High prevalence of right ventricular dysfunction in ICD patients with shocks: a potential new predictor in risk stratification.

BACKGROUND: Despite identifying several risk factors for sudden cardiac death, our ability to predict arrhythmic events in patients with an implantable cardioverter defibrillator (ICD) remains poor. The purpose of this study was to determine if patients who received appropriate ICD shocks had a higher degree of right ventricular (RV) dysfunction at baseline when compared to patients who did not receive ICD shocks. METHODS: We conducted a 1:2 case-control, retrospective study comparing RV end-diastolic and end-systolic areas (RV ED and RV ES areas, respectively), fractional RV area change, and RV wall thickness in 19 consecutive patients who received appropriate ICD shocks (shock group) with another group of 38 patients who did not receive ICD shocks (no-shock group). RESULTS: There was no significant difference in the RV end-diastolic areas between the groups. However, patients who experienced ICD shocks had a higher RV end-systolic area and a lower RV fractional area change when compared to patients without ICD shocks, 16.3 ± 4.9 cm(2) and 27.7 ± 9.0% in the shock group versus 14.2 ± 4.4 cm(2) and 35.8 ± 10.3% in the no-shock group; (p = 0.08 and 0.004, respectively). Furthermore, the RV wall thickness was greater in patients with ICD shocks when compared to patients without ICD shocks, 0.49 ± 0.05 cm and 0.44 ± 0.04 cm, respectively (p = 0.001). Utilizing a logistic regression analysis and after controlling for variables with univariate significance (p < 0.1), RV wall thickness independently predicted ICD shocks (OR 13.9 mm(-1) change of RV thickness, p = 0.004). CONCLUSION: Our findings suggest that some measurements of RV function might prove to be useful in predicting future arrhythmic events. Additional prospective studies are needed to test this hypothesis.

An animal model for ectopy-induced cardiomyopathy.

BACKGROUND: Ectopy-induced cardiomyopathy is an increasingly recognized cause of reversible left ventricular (LV) dysfunction. The underlying mechanisms remain unknown. Our goal was to create an animal model for ectopy-induced cardiomyopathy. METHODS: Eleven mongrel dogs underwent the implantation of a dual-chamber pacemaker. Four dogs served as the control group and seven as the paced group. In the paced group, the pacemaker was connected to two endocardial right ventricular leads, one inserted into the atrial port and the other one into the ventricular port with an atrioventricular delay adjusted to ensure the presence of coupled pacing simulating ventricular bigeminy. Echocardiographic measurements of LV size (LV end-diastolic diameter [LV-EDD], LV end-systolic diameter [LV-ESD]), LV ejection fraction (LVEF), and mitral regurgitation (MR) were obtained at baseline and after 4 weeks of monitoring or pacing in all dogs except one who had lead dislodgement. RESULTS: In the control group (n = 4), no significant changes in LV dimensions or function were noted. In the paced group (n = 6), LV-EDD and LV-ESD increased from 3.58 ± 0.65 cm and 2.47 ± 0.55 cm to 4.15 ± 0.59 cm and 3.21 ± 0.47 cm, respectively (P < 0.01). In addition, LVEF decreased from 60 ± 7% to 46 ± 9% (P < 0.05). No changes in MR were noted. CONCLUSION: We have shown that coupled pacing simulating ventricular bigeminy was feasible and resulted in increased LV dimensions and decreased LV function. By controlling the percentage of pacing, the coupling interval and the location of the pacing lead, this new model will allow the assessment of the relative roles of these variables in the development of ectopy-induced cardiomyopathy.

Improved heart rate recovery after marked weight loss induced by gastric bypass surgery: two-year follow up in the Utah Obesity Study.

BACKGROUND: Obesity is associated with significantly increased cardiovascular mortality that has been attributed, in part, to sympathetic activation. Gastric bypass surgery (GBS) appears to increase long-term survival in the severely obese, but the mechanisms responsible for this increase are still being sought. Heart rate (HR) recovery after exercise reflects the balance of cardiac autonomic input from the sympathetic and parasympathetic systems. Blunted HR recovery is a very powerful predictor of increased mortality, whereas enhanced HR recovery portends a good prognosis. OBJECTIVE: The purpose of this study was to evaluate the effect of marked weight loss achieved via GBS on HR recovery. METHODS: Severely obese patients underwent submaximal exercise testing (80% predicted maximum HR) at baseline and 2 years after GBS (n = 153) or nonsurgical treatment (n = 188). RESULTS: Patients in the GBS group lost an average of 100 ± 37 lb compared to 3 ± 22 lb in the nonsurgical group (P <.001, GBS vs nonsurgical). Resting HR decreased from 73 bpm to 60 bpm in the GBS group and from 74 bpm to 68 bpm in nonsurgical patients (P <.001). HR recovery improved by 13 bpm in the GBS group but did not change in the nonsurgical group (P <.001 GBS vs nonsurgical). In multivariable analysis, the independent correlates of HR recovery at the 2-year time point were resting HR, treadmill time, age, body mass index, and HOMA-IR (an index of insulin resistance). CONCLUSION: Marked weight loss 2 years after GBS resulted in a significant decrease in resting HR and an enhancement in HR recovery after exercise. These changes likely are attributable to improvement in insulin sensitivity and cardiac autonomic balance. Whether and to what extent this contributes to a reduction in cardiovascular mortality with GBS remains to be determined.

Reverse electrical remodeling of the ventricles following successful restoration of sinus rhythm in patients with persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) has been shown to be associated with reduced survival and increased ventricular arrhythmogenesis. The purpose of this study was to assess the effects of AF with adequate rate control on the electrophysiologic properties of the ventricles. We hypothesized that AF results in increased ventricular arrhythmogenic risk and that reverse remodeling occurs post-successful cardioversion. METHODS: In nine patients with persistent AF, we recorded 12-lead electrocardiograms (ECGs) and 1-hour high-resolution Holter ECGs (H12+, Mortara Instrument, Inc. Milwaukee, WI, USA; recorders [1000 sps] immediately following cardioversion (Day 1) and after 30 days of maintaining sinus rhythm (Day 30). We measured QTc, QT dispersion, and calculated estimates of mean ventricular action potential duration (RT), diastolic interval (DI), T-wave width (TW), T-wave peak-to-end, and their respective scatter on Day 1 and Day 30. Maintenance of normal sinus rhythm was confirmed with a weekly trans-telephonic ECG transmission. RESULTS: The average QTc interval decreased from 449 ± 28 ms on Day 1 to 422 ± 36 ms on Day 30 (P = 0.04). There was no significant difference in the average QT dispersion. A significant decrease was also noted in DI and TW scatter at Day 30 when compared with Day 1 (P = 0.03 and 0.04, respectively). A decrease in RT scatter was also noted albeit not statistically significant (P = 0.07). CONCLUSION: Our results suggest a greater propensity to ventricular arrhythmogenesis in the immediate period following restoration of sinus rhythm and reverse electrical remodeling of the ventricles during the first month after successful maintenance of sinus rhythm. (PACE 2010; 33:1198-1202).

The effects of rate and rhythm control on blood pressure and antihypertensive drug usage in patients with atrial fibrillation and hypertension enrolled in the AFFIRM trial.

INTRODUCTION: Atrial fibrillation (AF) has been shown to be associated with activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and increased sympathetic activity, all of which could lead to hypertension (HTN). While the effects of HTN on AF incidence and arrhythmogenesis have been reported, the long-term effects of AF on blood pressure (BP) remain unknown. We hypothesized that a rate control strategy is associated with an increase in BP and/or antihypertensive drug therapy when compared with a rhythm control strategy in patients with a history of AF and HTN. METHODS AND RESULTS: Using the intention to treat method, BP readings and the number of antihypertensive medication categories were analyzed over the first year of follow-up in patients with AF and HTN enrolled in the AFFIRM trial. No clinically significant changes in BP occurred. Medication data were available in 2,876 patients. In the rate control group, 27.8% of patients required a net increase in the number of antihypertensive medications when compared to 18.3% in the rhythm control group (P < 0.001). Furthermore, 27.1% of patients in the rate control group had a net decrease in the number of antihypertensive medications when compared with 41.7% in the rhythm control group (P < 0.001). CONCLUSIONS: Our findings suggest that AF could be contributing to BP elevation in patients with a history of HTN and that a rhythm control strategy might result in a decrease in BP in these patients. This hypothesis however, requires future testing.

High-frequency ventricular ectopy can increase sympathetic neural activity in humans.

BACKGROUND: Sudden cardiac death is usually caused by ventricular arrhythmias and in many cases, is preceded by frequent ventricular ectopy. It is known that ectopic beats cause transient increases in sympathetic nerve activity (SNA). OBJECTIVE: Because high SNA is known to be arrhythmogenic, we hypothesized that high rates of ectopy increase SNA, thereby creating a milieu that favors development of ventricular tachycardia and/or fibrillation. METHODS: This study measured muscle SNA, coronary sinus catecholamine, and arterial pressure during graded rates of ventricular ectopy (from 4:1 to 1:1, sinus to ectopic beat ratio) in a total of 21 patients referred for electrophysiologic testing. RESULTS: Both muscle SNA and coronary sinus norepinephrine increased significantly with increased ectopy frequency (P < .05). Moreover, the change in muscle SNA correlated significantly with the change in coronary sinus norepinephrine levels (r = .72, P < .001). CONCLUSION: These data demonstrate that sympathoexcitation evoked by high rates of ventricular ectopy can contribute to a state of elevated SNA both in peripheral tissues and within the heart. This altered autonomic state may contribute to an increased susceptibility to life-threatening tachyarrhythmias in patients with high rates of ectopy.