Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice.

BACKGROUND: Renal denervation (RDN) is an invasive intervention to treat drug-resistant arterial hypertension. Its therapeutic value is contentious. Here we examined the effects of RDN on inflammatory and infectious kidney disease models in mice. METHODS: Mice were unilaterally or bilaterally denervated, or sham operated, then three disease models were induced: nephrotoxic nephritis (NTN, a model for crescentic GN), pyelonephritis, and acute endotoxemic kidney injury (as a model for septic kidney injury). Analytical methods included measurement of renal glomerular filtration, proteinuria, flow cytometry of renal immune cells, immunofluorescence microscopy, and three-dimensional imaging of optically cleared kidney tissue by light-sheet fluorescence microscopy followed by algorithmic analysis. RESULTS: Unilateral RDN increased glomerular filtration in denervated kidneys, but decreased it in the contralateral kidneys. In the NTN model, more nephritogenic antibodies were deposited in glomeruli of denervated kidneys, resulting in stronger inflammation and injury in denervated compared with contralateral nondenervated kidneys. Also, intravenously injected LPS increased neutrophil influx and inflammation in the denervated kidneys, both after unilateral and bilateral RDN. When we induced pyelonephritis in bilaterally denervated mice, both kidneys contained less bacteria and neutrophils. In unilaterally denervated mice, pyelonephritis was attenuated and intrarenal neutrophil numbers were lower in the denervated kidneys. The nondenervated contralateral kidneys harbored more bacteria, even compared with sham-operated mice, and showed the strongest influx of neutrophils. CONCLUSIONS: Our data suggest that the increased perfusion and filtration in denervated kidneys can profoundly influence concomitant inflammatory diseases. Renal deposition of circulating nephritic material is higher, and hence antibody- and endotoxin-induced kidney injury was aggravated in mice. Pyelonephritis was attenuated in denervated murine kidneys, because the higher glomerular filtration facilitated better flushing of bacteria with the urine, at the expense of contralateral, nondenervated kidneys after unilateral denervation.

Electrical storm: Prognosis and management.

Electrical storm is present when a cluster of ventricular arrhythmias (VAs) occurs within a short time frame. The most widely accepted definition is 3 or more episodes of VA within a 24-h period, although prognostic risk begins to rise when 2 or more events occur within 3months. Electrical storm often presents as a medical emergency in the form of recurrent implantable cardiac defibrillator (ICD) shocks, recurrent syncope in patients with no ICD or low cardiac output symptoms. Management often requires a multimodality approach including ICD management, pharmacologic therapy, catheter ablation and modulations of the autonomic nervous system. In this article, we review the definition, prognosis and management of electrical storm.

Surgical Treatment of Atrial Fibrillation.

The surgical treatment of atrial fibrillation (AF) has evolved significantly over the last 20 years and even more so in the last 5 years. There are now many clinically successful surgical procedures focused on eliminating AF and AF-related stroke. This review discusses the current types of surgical AF procedures, including minimally invasive and hybrid, and may assist clinicians in understanding the various surgical AF options available to patients today.

Effect of renal denervation on long-term outcomes in patients with resistant hypertension.

Increasing studies strongly prove that renal denervation, a minimally invasive surgery, is a promising new non-drug treatment method that can effectively control blood pressure in patients with resistant hypertension, but the evaluation of the long-term blood pressure control effect of renal denervation for resistant hypertension is still lacking. Here, we critically review current long-term follow-up data about the use of renal denervation for RH to comprehensively evaluate the effectiveness of renal denervation for RH, and to provide practical guidance for practitioners who are establishing a renal denervation service. Limited by the current research, many problems need to be solved before renal denervation is applied to RH. In addition, ambulatory blood pressure should be the first choice for the evaluation of blood pressure. Finally, the continuous antihypertensive effect of renal denervation in different renal denervation systems also needs to be strictly compared.

Neuroscientific therapies for atrial fibrillation.

The cardiac autonomic nervous system (ANS) plays an integral role in normal cardiac physiology as well as in disease states that cause cardiac arrhythmias. The cardiac ANS, comprised of a complex neural hierarchy in a nested series of interacting feedback loops, regulates atrial electrophysiology and is itself susceptible to remodelling by atrial rhythm. In light of the challenges of treating atrial fibrillation (AF) with conventional pharmacologic and myoablative techniques, increasingly interest has begun to focus on targeting the cardiac neuraxis for AF. Strong evidence from animal models and clinical patients demonstrates that parasympathetic and sympathetic activity within this neuraxis may trigger AF, and the ANS may either induce atrial remodelling or undergo remodelling itself to serve as a substrate for AF. Multiple nexus points within the cardiac neuraxis are therapeutic targets, and neuroablative and neuromodulatory therapies for AF include ganglionated plexus ablation, epicardial botulinum toxin injection, vagal nerve (tragus) stimulation, renal denervation, stellate ganglion block/resection, baroreceptor activation therapy, and spinal cord stimulation. Pre-clinical and clinical studies on these modalities have had promising results and are reviewed here.

Atrial fibrillation in obstructive sleep apnea: Neural mechanisms and emerging therapies.

Obstructive sleep apnea (OSA) has been reproducibly identified as a risk factor for initiation and progression of atrial fibrillation (AF) and reduces the efficacy of antiarrhythmic drugs, electrical cardioversion, and catheter ablation in AF. It is still controversial whether continuous positive airway pressure ventilation (CPAP) could improve the successful rate of AF treatment in OSA patients. Besides, CPAP has shown relative low compliance in patients with OSA. Therefore, novel optional therapies might be needed to improve the control of AF associated with OSA. A growing body of evidence suggests that autonomic activation contributes to the pathogenesis of AF in OSA. Acute apneic episodes result in sympathovagal co-activation, shortening atrial refractoriness and promoting the initiation of AF. Chronic OSA-induced sympathetic activation plays a crucial role in atrial autonomic, structural, and electrical remodeling, thus providing substrates for AF maintenance and recurrence. Therefore, the autonomic nervous system may be a promising therapeutic target for OSA and AF. Autonomic modulation as a treatment for OSA-associated AF has been well established in several preclinical studies. Further clinical studies are needed to provide a more precise definition of the role of autonomic modulation in the treatment of AF in OSA.

Stimulation Mapping of the Pulmonary Artery for Denervation Procedures: an Experimental Study.

Transcatheter pulmonary artery denervation (PADN) has been developed for the correction of pulmonary hypertension. We investigated pulmonary artery stimulation mapping and its role in PADN procedures. Artery stimulation was performed in 17 Landrace pigs. Low-frequency stimulation defined areas of ventricular and atrial capture. High-frequency stimulation evoked the following responses: sinus rhythm slowing and/or atrial rhythm acceleration in 59% of animals, phrenic nerve capture in 100%, and laryngeal recurrent nerve capture in 23%. The sites with evoked heart rate responses were marked by discrete radiofrequency ablations (RFA). An autopsy showed nerves in the adventitia and perivascular fat under the RFA sites, and the lack of muscarinic-1, tyrosine hydroxylase, and dopamine-5 receptors' expression. During PADN, areas adjacent to the course of phrenic and recurrent laryngeal nerves should be avoided. RFA at points with heart rate responses leads to the non-reproducibility of evoked reactions and the disappearance of neural markers' expression. Graphical abstract.

Intravascular Ultrasound Pulmonary Artery Denervation to Treat Pulmonary Arterial Hypertension (TROPHY1): Multicenter, Early Feasibility Study.

OBJECTIVES: The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) on a minimum of dual oral therapy. BACKGROUND: Early studies have suggested that PDN can reduce PVR in patients with PAH. METHODS: TROPHY1 (Treatment of Pulmonary Hypertension 1) was a multicenter, international, open-label trial undertaken at 8 specialist centers. Patients 18 to 75 years of age with PAH were eligible if taking dual oral or triple nonparenteral therapy and not responsive to acute vasodilator testing. Eligible patients underwent PDN (TIVUS System). The primary safety endpoint was procedure-related adverse events at 30 days. Secondary endpoints included procedure-related adverse events, disease worsening and death to 12 months, and efficacy endpoints that included change in pulmonary hemodynamic status, 6-min walk distance, and quality of life from baseline to 4 or 6 months. Patients were to remain on disease-specific medication for the duration of the study. RESULTS: Twenty-three patients underwent PDN, with no procedure-related serious adverse events reported. The reduction in PVR at 4- or 6-month follow-up was 94 ± 151 dyn·s·cm-5 (p = 0.001) or 17.8%, which was associated with a 42 ± 63 m (p = 0.02) increase in 6-min walk distance and a 671 ± 1,555 step (p = 0.04) increase in daily activity. CONCLUSIONS: In this multicenter early feasibility study, PDN with an intravascular ultrasound catheter was performed without procedure-related adverse events and was associated with a reduction in PVR and increases in 6-min walk distance and daily activity in patients with PAH on background dual or triple therapy.

Conceptual Considerations for Device-Based Therapy in Acute Decompensated Heart Failure: DRI2P2S.

Acute decompensated heart failure remains the most common cause of hospitalization in older adults, and studies of pharmacological therapies have yielded limited progress in improving outcomes for these patients. This has prompted the development of novel device-based interventions, classified mechanistically based on the way in which they intend to improve central hemodynamics, increase renal perfusion, remove salt and water from the body, and result in clinically meaningful degrees of decongestion. In this review, we provide an overview of the pathophysiology of acute decompensated heart failure, current management strategies, and failed pharmacological therapies. We provide an in depth description of seven investigational device classes designed to target one or more of the pathophysiologic derangements in acute decompensated heart failure, denoted by the acronym DRI2P2S. Dilators decrease central pressures by increasing venous capacitance through splanchnic nerve modulation. Removers remove excess fluid through peritoneal dialysis, aquaphoresis, or hemodialysis. Inotropes directly modulate the cardiac nerve plexus to enhance ventricular contractility. Interstitial devices enhance volume removal through lymphatic duct decompression. Pushers are novel descending aorta rotary pumps that directly increase renal artery pressure. Pullers reduce central venous pressures or renal venous pressures to increase renal perfusion. Selective intrarenal artery catheters facilitate direct delivery of short acting vasodilator therapy. We also discuss challenges posed in clinical trial design for these novel device-based strategies including optimal patient selection and appropriate end points to establish efficacy.

Renal denervation: dark past, bright future?

The purpose of this review is to update the reader on the relevance of autonomic nervous system imbalance in clinical cardiology. Increased sympathetic tone associates with the metabolic syndrome, hypertension and cardiac arrhythmias. With the kidneys playing a pivotal role in increased peripheral resistance, sodium and water retention and other mechanisms, renal denervation (RD) may theoretically restore autonomic imbalance and improve cardiovascular outcomes. Landmark RD trials and novel uses for RD in cardiac arrhythmia management are discussed.

Different effects of additional ganglion plexus ablation on catheter and surgical ablation for atrial fibrillation: a systemic review and meta-analysis.

The effect of ganglion plexus (GP) ablation in addition to pulmonary veins isolation (PVI) for atrial fibrillation (AF) remained controversial between the catheter and surgical-based studies. Eleven studies (five randomized controlled trials and six nonrandomized studies) of 1750 patients were included in a meta-analysis to elucidate the incremental benefit of additional GP ablation in patients undergoing catheter or surgical ablation. Risk ratios were calculated for freedom from AF or AT recurrence after a single procedure. Additional GP ablation was associated with a better rhythm outcome for patients undergone catheter ablation but did not seem to increase freedom from AF/AT for surgical patients. Both paroxysmal and non-paroxysmal AF showed a positive outcome comparing additional GP ablation with PVI alone.

Renal denervation in patients with heart failure secondary to Chagas' disease: A pilot randomized controlled trial.

INTRODUCTION: Chagas disease is one of the most relevant endemic parasitic diseases in Latin America, affecting approximately 6 million people. Overt Chagas heart disease is an ominous condition, occurring in 20-30% of infected individuals, which has besides the persistent myocarditis a peculiar intracardiac ganglionic neuronal depletion and dysautonomy. This study aims to evaluate the safety and feasibility of renal denervation for patients with advanced symptomatic Chagas cardiomyopathy. METHODS: Open-label prospective pilot study that randomized patients with Chagas heart disease to either renal denervation or conservative treatment (2:1 ratio). The primary endpoint was the incidence of major adverse events at 9 months, defined as a composite of all-cause death, myocardial infarction, stroke, need for renal artery invasive treatment, or worsening renal function. RESULTS: A total of 17 patients were allocated for renal denervation (n = 11) or conservative treatment (n = 6). Included patients had severe symptomatic heart disease, with markedly depressed left ventricular function (average ejection fraction 26.7 ± 4.9%). For patients randomized to renal denervation, the procedure was performed successfully and uneventfully. After 9 months, the primary endpoint occurred in 36.4% of patients in the renal denervation group and 50.0% in the control arm (p = .6). After 9 months, clinical, laboratory, functional, echocardiographic, and quality of life parameters were similar between groups. CONCLUSIONS: This pilot study suggests that renal denervation is safe and feasible in patients with Chagas cardiomyopathy, warranting future studies to better evaluate the clinical efficacy of the interventional strategy in improving the prognosis of this high-risk population.

Patient preference for therapies in hypertension: a cross-sectional survey of German patients.

BACKGROUND: Hypertension is poorly controlled in numerous patients despite effective medication being available. Catheter-based renal denervation (RDN) has emerged as an alternative treatment option. We aimed to assess how likely patients with elevated blood pressure (BP) are to accept RDN as treatment option. METHODS: A questionnaire-based cross-sectional survey was performed in patients with elevated BP in Germany. Data on patient demographics, clinical characteristics and treatment preferences were collected, anonymized and analyzed. RESULTS: One thousand and eleven patients completed the survey. Mean age was 66 years (55% male). If not already on medication (n = 172), 38.2% of patients would prefer RDN. Of those already on drug therapy (n = 839), 28.2% would opt for RDN. Patients who were pro-RDN were younger (p < 0.0001) and more often male (p < 0.0001). Nineteen percent would choose RDN if it lowered systolic BP by at least 20 mmHg, more than 40% if they did not have to take any more pills thereafter, and 30% if it would lower BP by at least 10 mmHg. Experiences of side effects and drug adherence were identified as determinants of patient preference. Physicians were the main source of information regarding medical problems (95.5%) and influence patients' decision regarding therapies (98%). CONCLUSIONS: This survey found that a significant proportion of patients would choose catheter-based RDN over lifelong pharmacotherapy. These patients were younger and more likely to be male but their expectation of the extent of BP decrease with RDN was high. Physicians are key mediators for treatment selection. They need to incorporate patient preferences into shared decision making.

Pulmonary Artery Denervation Significantly Increases 6-Min Walk Distance for Patients With Combined Pre- and Post-Capillary Pulmonary Hypertension Associated With Left Heart Failure: The PADN-5 Study.

OBJECTIVES: The authors sought to assess the benefits of pulmonary artery denervation (PADN) among combined pre- and post-capillary pulmonary hypertension (CpcPH) patients in a prospective, randomized, sham-controlled trial. BACKGROUND: PADN has been shown to improve hemodynamics of pulmonary arterial hypertension in a series of patients. Additionally, benefits of targeted medical therapy for patients with CpcPH secondary to left-sided heart failure are unknown. METHODS: Ninety-eight CpcPH patients, defined as mean pulmonary arterial pressure ≥25 mm Hg, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance (PVR) >3.0 Wood units (WU), were randomly assigned to PADN or sildenafil plus sham PADN. Standard medical therapy for heart failure was administered to all patients in both groups. The primary endpoint was the increase in the 6-min walk distance at the 6-month follow-up. The secondary endpoint was change in PVR. Clinical worsening was assessed in a post hoc analysis. The main safety endpoint was occurrence of pulmonary embolism. RESULTS: At 6 months, the mean increases in the 6-min walk distance were 83 m in the PADN group and 15 m in the sildenafil group (least square mean difference 66 m, 95% confidence interval: 38.2 to 98.8 m; p < 0.001). PADN treatment was associated with a significantly lower PVR than in the sildenafil group (4.2 ± 1.5 WU vs. 6.1 ± 2.9 WU; p = 0.001). Clinical worsening was less frequent in the PADN group compared with the sildenafil group (16.7% vs. 40%; p = 0.014). At the end of the study, there were 7 all-cause deaths and 2 cases of pulmonary embolism. CONCLUSIONS: PADN is associated with significant improvements in hemodynamic and clinical outcomes in patients with CpcPH. Further studies are warranted to define its precise role in the treatment of this patient population. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335).

Endovascular Denervation: A New Approach for Cancer Pain Relief?

PURPOSE: To evaluate the effects of endovascular denervation (EDN) on abdominal cancer pain relief. MATERIALS AND METHODS: From April 2017 to February 2018, 7 cancer patients (2 males and 5 females) were enrolled in this study. The diagnoses of the patients included 3 pancreatic cancer, 2 cervical carcinoma, 1 cholangiocarcinoma, and 1 esophageal cancer with retroperitoneum lymph nodes invasion. Denervation was carried out at the abdominal aorta close to the origin of celiac artery and superior mesenteric artery with the use of a multielectrode radiofrequency ablation catheter with settings of time 120 seconds and temperature 60°C. The primary end point was improvement in pain scores. The secondary end points included change in quality of life, intake of narcotics, and the safety of EDN. RESULTS: All of the patients experienced pain relief. The pain scores as measured by means of visual analog scores at 1, 2, 4, 8, and 12 weeks after the procedure were significantly lower than before the operation (P < .001). A > 4 score reduction was observed in all cases. A significant reduction in narcotics use within 3 months after the operation was also seen. The quality of life scores of the patients improved significantly (P < .005) with better sleep. No severe treatment-related adverse events or major complications were observed. CONCLUSIONS: EDN is a safe and effective means to alleviate pain caused by cancer and may serve as a new approach for cancer pain relief and palliative care.

A rat study of the use of end-to-side peripheral nerve repair as a "babysitting" technique to reduce the deleterious effect of chronic denervation.

OBJECTIVE: Functional recovery is disappointing after surgical repair of nerves that are injured far from their target organs and/or after delayed repair. In the former case, a nerve transfer that transects a distal nerve fascicle to innervate denervated targets is one strategy to promote nerve regeneration and functional recovery. An alternate strategy tested in this study is to perform an end-to-side neurorrhaphy to "babysit" (protect) the denervated distal nerve stump at the time of nerve repair and reduce the deleterious effect of chronic denervation on nerve regeneration. METHODS: In the hindlimbs of Sprague-Dawley rats, the common peroneal (CP) nerve was transected unilaterally and the distal CP nerve stump inserted through a perineurial window into the intact tibial (TIB) nerve, i.e., CP-TIB end-to-side neurorrhaphy. In the first experiment, TIB nerve motoneurons that had regenerated and/or sprouted axons into the CP nerve within 3 months were stimulated to elicit contractions, and thereafter, identified with retrograde dyes for counting. In the second experiment, the intact TIB nerve was transected and cross-sutured to a 3-month chronically denervated distal CP nerve stump that had either been "protected" by ingrown TIB nerves after CP-TIB neurorrhaphy or remained chronically denervated. Thereafter, the number of retrogradely labeled TIB nerve motoneurons that had regenerated their nerves within 3 months were counted and reinnervated tibialis anterior (TA) muscles weighed. RESULTS: A mean (± SE) of 231 ± 83 TIB nerve motoneurons grew into the end-to-side CP distal nerve stump with corresponding ankle flexion; 32% regenerated their axons and 24% sprouted axons from the intact TIB nerve, eliciting ankle flexor-extensor co-contraction. In the second experiment, after a 3-month period of TIB nerve regeneration, significantly more TIB motoneurons regenerated their axons into "protected" than "unprotected" CP distal nerve stumps within 3 months (mean 332 ± 43.6 vs 235 ± 39.3 motoneurons) with corresponding and significantly higher numbers of regenerated nerve fibers, resulting in significantly better recovery of reinnervated TA muscle weight. CONCLUSIONS: These experiments in rats demonstrated that delayed nerve repair is more effective when the deleterious effects of chronic denervation of the distal nerve stump are reduced by protecting the nerve stump with ingrowing nerve fibers across an end-to-side insertion of the distal nerve stump into a neighboring intact nerve. Such an end-to-side neurorrhaphy may be invaluable as a means of preventing the atrophy of distal nerve stumps and target organs after chronic denervation, which allows for effective reinnervation of the protected distal nerve stumps and target organs over distance and time.

Cost-Effectiveness of Renal Denervation Therapy for Treatment-Resistant Hypertension: A Best Case Scenario.

BACKGROUND: Renal denervation (RDN) is effective at reducing blood pressure (BP) among patients with treatment-resistant hypertension (TRH). However, recent findings regarding the effectiveness of RDN for BP reduction compared with standard treatment of care (SoC) has initiated a rigorous debate about its role in TRH management. In this study, we sought to determine the thresholds for cardiovascular risk and costs of RDN which would make RDN cost-effective. METHODS: A Markov model was constructed to simulate cardiovascular events over a lifetime among TRH subjects aged 60 years at baseline, and without prior cardiovascular disease. The effect on lowering BP was based on results observed in clinical trials of RDN undertaken to date, and the expected subsequent change to cardiovascular risk was drawn from a published meta-regression. Cost and utility data were drawn from published sources. Incremental cost-effectiveness ratios (ICER) in terms of Australian dollars (AUD) per life year and per quality-adjusted life year (QALY) gained were estimated to assess RDN cost-effectiveness relative to SoC from the Australian health care perspective, assuming a willingness-to-pay threshold of AUD 50,000. RESULTS: Over a lifetime horizon, the model predicted that at the current estimated costs of RDN (AUD 9531/€6573, 1€ = 1.45 AUD), it would be cost-effective only if it was targeted to patients whose 10-year predicted cardiovascular risk was at least 13.2% initially. The ICERs (discounted) were AUD 49,519 per life year gained and AUD 47,130 per QALY gained. CONCLUSIONS: At current costs and based on currently observed effects on BP reduction, RDN would be cost-effective among patients with TRH.

First-in-Man Experience with a Novel Catheter-Based Renal Denervation System of Ultrasonic Ablation in Patients with Resistant Hypertension.

PURPOSE: To report results of renal denervation (RDN) with the first catheter-based, non-balloon occlusion ultrasonic system in patients with resistant hypertension. MATERIALS AND METHODS: In a multicenter, single-arm trial, 39 patients with resistant hypertension (defined as uncontrolled hypertension while taking ≥ 3 antihypertensive medications) were treated. The cohort consisted of 4 groups: severe resistant hypertension (office systolic blood pressure [OSBP] ≥ 160 mm Hg) treated with a unidirectional catheter (group 1; n = 14); severe resistant hypertension treated with a multidirectional catheter (group 2; n = 18); moderate resistant hypertension (OSBP 140-159 mm Hg) treated with a multidirectional catheter (group 3; n = 5); and recurrent severe resistant hypertension, after an initial response to RF RDN (group 4; n = 2). Blood pressure monitoring was performed for 6 months. RESULTS: Severe adverse events were not noted immediately after the procedure or during follow-up. Treatment time was longer with unidirectional than with multidirectional catheters (36.7 min ± 9.6 vs 11.9 min ± 5.8; P < .001). Mean reductions in office blood pressure (systolic/diastolic) at 1, 3, and 6 months were -26.1/-9.6 mm Hg, -28.0/-9.9 mm Hg, and -30.6/-14.1 mm Hg (P < .01 for all). Per-group analysis showed significant OSBP reduction for groups 1 and 2. Patients with isolated systolic hypertension had a significantly smaller reduction in OSBP after 6 months compared with patients with combined systolic/diastolic hypertension (-16.2 mm Hg ± 18.5 vs -9.9 mm Hg ± 33.4; P < .005). CONCLUSIONS: Use of the RDN system was feasible and safe in this phase I study. Significant blood pressure reductions were observed over 6 months, although less in patients with isolated systolic hypertension.

Quality of life improves after thoracoscopic surgical ablation of advanced atrial fibrillation: Results of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study.

OBJECTIVE: We evaluated health-related quality of life at 12 months after thoracoscopic surgical ablation in patients enrolled in the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study. The Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery study assessed the efficacy and safety of ganglion plexus ablation in patients with symptomatic advanced atrial fibrillation undergoing thoracoscopic surgical ablation. METHODS: Patients (n = 240) underwent thoracoscopic pulmonary vein isolation with additional ablation lines in patients with persistent atrial fibrillation. Subjects were randomized to additional ganglion plexus ablation or control. Short Form 36 quality of life questionnaires were collected at baseline and at 6 and 12 months of follow-up. RESULTS: A total of 201 patients were eligible for quality of life analysis (age 59 ± 8 years, 72% were men, 68% had an enlarged left atrium, 57% had persistent atrial fibrillation). Patients improved in physical and mental health at 6 months (both P < .01) and 12 months (both P < .01) relative to baseline, with no difference between the ganglion plexus (n = 101) and control (n = 100) groups. Short Form 36 subscores in patients with 1 or no atrial fibrillation recurrences were similar to those in the general Dutch population after 12 months. Patients with multiple atrial fibrillation recurrences (30%) improved in mental (P < .01), but not physical health, and 6 of 8 Short Form 36 subscales remained below those of the general Dutch population. Patients with irreversible, but not with reversible procedural complications had persistently diminished quality of life scores at 12 months. CONCLUSIONS: Thoracoscopic surgery for advanced atrial fibrillation results in improvement in quality of life, regardless of additional ganglion plexus ablation. Quality of life in patients with no or 1 atrial fibrillation recurrence increased to the level of the general Dutch population, whereas in patients with multiple atrial fibrillation recurrences quality of life remained lower. Irreversible but not reversible procedural complications were associated with persistently lower quality of life.