Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD.

BACKGROUND: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown. METHODS: Left atrial (LA) fibrosis was analyzed in samples from patients with AF and concomitant CKD (estimated glomerular filtration rate [eGFR], <60 mL/min per 1.73 m2) using picrosirius red and compared with AF patients without CKD and patients with sinus rhythm with and without CKD. In a translational approach, male Sprague Dawley rats were fed with 0.25% adenine (AD)-containing chow for 16 weeks to induce CKD. At week 5, AD-fed rats underwent RDN or sham operation (AD). Rats on normal chow served as control. After 16 weeks, cardiac function and AF susceptibility were assessed by echocardiography, radiotelemetry, electrophysiological mapping, and burst stimulation, respectively. LA tissue was histologically analyzed for sympathetic innervation using tyrosine hydroxylase staining, and LA fibrosis was determined using picrosirius red. RESULTS: Sirius red staining demonstrated significantly increased LA fibrosis in patients with AF+CKD compared with AF without CKD or sinus rhythm. In rats, AD demonstrated LA structural changes with enhanced sympathetic innervation compared with control. In AD, LA enlargement was associated with prolonged duration of induced AF episodes, impaired LA conduction latency, and increased absolute conduction inhomogeneity. RDN treatment improved LA remodeling and reduced LA diameter compared with sham-operated AD. Furthermore, RDN decreased AF susceptibility and ameliorated LA conduction latency and absolute conduction inhomogeneity, independent of blood pressure reduction and renal function. CONCLUSIONS: In an experimental rat model of CKD, RDN inhibited progression of atrial structural and electrophysiological remodeling. Therefore, RDN represents a potential therapeutic tool to reduce the risk of AF in CKD, independent of changes in renal function and blood pressure.

Clinical Trial Design Principles and Outcomes Definitions for Device-Based Therapies for Hypertension: A Consensus Document From the Hypertension Academic Research Consortium.

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis.

BACKGROUND: Novel pacing technologies, such as His bundle pacing (HBP) and left bundle branch area pacing (LBBaP), have emerged to maintain physiological ventricular activation. We investigated the outcomes of LBBP with HBP for patients requiring a de novo permanent pacing. METHODS AND RESULTS: Systematic review of randomized clinical trials and observational studies comparing LBBaP with HBP until March 01, 2023 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included pacing metrics, QRS duration, lead revision, procedure parameters, all-cause mortality and heart failure hospitalization (HFH). Overall, 10 studies with 1596 patients were included. Implant success rate was higher in LBBaP compared with HBP (RR 1.24, 95% CI: 1.08 to 1.42, p = .002). LBBaP was associated with lower capture threshold at implantation (mean difference (MD) -0.62 V, 95% CI: -0.74 to -0.51 V, p < .0001) and at follow-up (MD -0.74 V, 95% CI: -0.96 to -0.53, p < .0001), shorter procedure duration (MD -14.66 min, 95% CI: -23.54 to -5.78, p = .001) and shorter fluoroscopy time (MD -4.2 min, 95% CI: -8.4 to -0.0, p = .05). Compared with HBP, LBBaP was associated with a decreased risk of all-cause mortality (RR: 0.50, 95% CI: 0.33 to 0.77, p = .002) and HFH (RR: 0.57, 95% CI: 0.33 to 1.00, p = .05). No statistical differences were found in lead revisions and QRS duration before and after pacing. CONCLUSION: This meta-analysis found that LBBaP was superior to HBP regarding pacing metrics and implant success rate as an initial pacing strategy, although absence of head-to-head randomized comparison warrants caution in interpretation of the results.

Renal denervation for the treatment of ventricular arrhythmias: A systematic review and meta-analysis.

INTRODUCTION: Ventricular arrhythmias (VAs) are a major cause of morbidity and mortality in patients with heart disease. Recent studies evaluated the effect of renal denervation (RDN) on the occurrence of VAs. We conducted a systematic review and meta-analysis to determine the efficacy and safety of this procedure. METHODS AND RESULTS: A systematic search of the literature was performed to identify studies that evaluated the use of RDN for the management of VAs. Primary outcomes were reduction in the number of VAs and implantable cardioverter-defibrillator (ICD) therapies. Secondary outcomes were changes in blood pressure and renal function. Ten studies (152 patients) were included in the meta-analysis. RDN was associated with a reduction in the number of VAs, antitachycardia pacing, ICD shocks, and overall ICD therapies of 3.53 events/patient/month (95% confidence interval [CI] = -5.48 to -1.57), 2.86 events/patient/month (95% CI = -4.09 to -1.63), 2.04 events/patient/month (95% CI = -2.12 to -1.97), and 2.68 events/patient/month (95% CI = -3.58 to -1.78), respectively. Periprocedural adverse events occurred in 1.23% of patients and no significant changes were seen in blood pressure or renal function. CONCLUSIONS: In patients with refractory VAs, RDN was associated with a reduction in the number of VAs and ICD therapies, and was shown to be a safe procedure.

Inducibility of atrial fibrillation after catheter ablation predicts recurrences of atrial fibrillation: a meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is a component of standard care for patients with symptomatic atrial fibrillation (AF). Procedural inducibility of AF following PVI has been suggested as predictor of AF recurrence but is discussed controversially. This meta-analysis aimed at evaluating the relevance of electrophysiological inducibility of AF following PVI for future AF recurrences. METHODS: A literature search of MEDLINE and Web of Science was performed until April 2020. Prospective trials of PVI in patients with AF and post-procedural atrial stimulation to test for inducibility of AF as well as adequate follow-up for AF recurrence (defined as AF >10 s to >10 min at follow-up) were included. Odds ratios (ORs) were analyzed using random-effects models. RESULTS: A total of 11 trials with 1544 patients (follow-up 7-39 months, age 56 ± 6 years, predominantly male 74 ± 6%) were included. Inducibility of AF post-PVI was predictive for AF recurrence during follow-up (OR 2.08; 95% CI 1.25 to 3.46). Prediction for AF recurrence at follow-up was better for patients with paroxysmal AF (OR 4.06; 95% CI 1.39 to 11.91), stimulation in the CS (OR 2.82, 95% CI 1.17 to 6.79). A trend towards higher ORs was seen without the use of isoproterenol (OR 2.43; 95% CI 1.17 to 5.07), as well as few stimulations during induction and a short definition of AF in meta-regression analyses. CONCLUSIONS: Electrophysiological inducibility of AF following PVI was predictive for future recurrence of AF, in particular in patients with paroxysmal AF, stimulation in only CS and no use of isoproterenol.

Mapping of an atrial tachycardia after Epicor™ high-intensity focused ultrasound ablation: A case report.

BACKGROUND: Surgical techniques, such as the application of high-intensity focused ultrasound (HIFU), can be used for pulmonary vein isolation (PVI). CASE SUMMARY: We report a case of a 73-year old patient, in whom HIFU failed to achieve PVI but promoted the occurrence of a scar-related atrial tachycardia (AT). Voltage mapping of the left atrium revealed multiple gaps along the ablation line. Coherent mapping with visualization of velocity vectors allowed the correct interpretation and the targeted ablation of the AT. DISCUSSION: Cardiac surgery can promote scar-related AT. The coherent mapping function could simplify the mapping of scar-related AT in the future.

Resting heart rate and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk analysis from the ONTARGET/TRANSCEND trials.

AIMS: Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes. METHODS AND RESULTS: We examined 30 937 patients aged 55 years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56 months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and χ2 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19 450 patients without diabetes and 11 487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P < 0.0001). In the categories of <60 bpm, 60 ≤ 65 bpm, 65 ≤ 70 bpm, 70 ≤ 75 bpm, 75 ≤ 80 bpm and ≥80 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75 ≤ 80 bpm (adjusted hazard ratio [HR] 1.17 (1.01-1.36)) compared to RHR 60 ≤ 65 bpm. For patients with in-trial RHR ≥80 bpm the hazard ratios were highest (diabetes: 1.96 (1.64-2.34), no diabetes: 1.73 (1.49-2.00), For cardiovascular death hazards were also clearly increased at RHR ≥80 bpm (diabetes [1.99, (1.53-2.58)], no diabetes [1.73 (1.38-2.16)]. Similar results were obtained for hospitalization for heart failure and all-cause death while the effect of RHR on myocardial infarction and stroke was less pronounced. Results were robust after adjusting for various risk indicators including beta-blocker use and atrial fibrillation. No significant association to harm was observed at lower RHR. CONCLUSION: Mean RHR above 75-80 b.p.m. was associated with increased risk for cardiovascular outcomes except for stroke. Since in diabetes, high RHR is associated with higher absolute event numbers and patients have higher RHRs, this association might be of particular clinical importance in diabetes. These data suggest that RHR lowering in patients with RHRs above 75-80 b.p.m. needs to be studied in prospective trials to determine if it will reduce outcomes in diabetic and non-diabetic patients at high cardiovascular risk. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov.Unique identifier: NCT00153101.

Ambulatory heart rate reduction after catheter-based renal denervation in hypertensive patients not receiving anti-hypertensive medications: data from SPYRAL HTN-OFF MED, a randomized, sham-controlled, proof-of-concept trial.

AIMS: The randomized sham-controlled SPYRAL HTN-OFF MED trial demonstrated that renal denervation (RDN) using a multi-electrode catheter lowers ambulatory blood pressure (BP) in non-medicated hypertensive patients. The current report describes the effects of RDN on heart rate (HR) in this population. METHODS AND RESULTS: Patients were enrolled with an office systolic BP (SBP) of ≥150 mmHg and <180 mmHg, office diastolic BP (DBP) of ≥90 mmHg, and a mean ambulatory SBP of ≥140 mmHg and <170 mmHg. Patients were drug naïve or removed from their anti-hypertensive medications. Eighty patients were randomized 1:1 to RDN or sham procedure. This post hoc analysis examines the effect at 3 months of RDN on HR and of high baseline 24-h HR on BP and HR changes. There was a significant reduction in 24-h HR at 3 months for the RDN group (-2.5 b.p.m.) compared with sham (-0.2 b.p.m.), P = 0.003 (analysis of covariance). Mean baseline-adjusted treatment differences were significantly different between groups at 3 months for average morning HR (-4.4 b.p.m., P = 0.046) and minimum morning HR (-3.0 b.p.m., P = 0.026). RDN patients with baseline 24-h HR above the median (73.5 b.p.m.) had significant reductions in average ambulatory SBP (-10.7 mmHg difference, P = 0.001) and DBP (-7.5 mmHg, P < 0.001), whereas BP changes in RDN patients with below-median HRs were not significant. CONCLUSION: Average and minimum morning HR were significantly reduced at 3 months for RDN compared with sham patients. A baseline 24-h HR above the median predicted greater BP reductions and may allow physicians to select patients likely to respond to the procedure.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Atrial fibrillation and gastroesophageal reflux disease: the cardiogastric interaction.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Multiple conditions like hypertension, heart failure, diabetes, sleep apnoea, and obesity play a role for the initiation and perpetuation of AF. Recently, a potential association between gastroesophageal reflux disease (GERD) and AF development has been proposed due to the close anatomic vicinity of the oesophagus and the left atrium. As an understanding of the association between acid reflux disease and AF may be important in the global multimodal treatment strategy to further improve outcomes in a subset of patients with AF, we discuss potential atrial arrhythmogenic mechanisms in patients with GERD, such as gastric and subsequent systemic inflammation, impaired autonomic stimulation, mechanical irritation due to anatomical proximity of the left atrium and the oesophagus, as well as common comorbidities like obesity and sleep-disordered breathing. Data on GERD and oesophageal lesions after AF-ablation procedures will be reviewed. Treatment of GERD to avoid AF or to reduce AF burden might represent a future treatment perspective but needs to be scrutinized in prospective trials.

Low-Level But Not High-Level Baroreceptor Stimulation Inhibits Atrial Fibrillation in a Pig Model of Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) increases susceptibility to atrial fibrillation (AF) by a combined sympatho-vagal hyperactivation. The purpose of this study was to investigate the effect of autonomic nervous system modulation by low-level baroreceptor stimulation (LL-BRS) compared to high-level BRS (HL-BRS) on atrial arrhythmogenic changes in a pig model of OSA. METHODS AND RESULTS: Sixteen pigs received tracheotomy under general urethane/chloralose anesthesia. Group 1 pigs (n = 8) received LL-BRS (at 80% of that slowing sinus rate) for 3 hours and group 2 pigs (n = 8) received HL-BRS (slowing sinus rate). Changes in atrial effective refractory period (AERP) and AF-inducibility were determined during applied negative thoracic pressure (NTP) for 2 minutes before and at the end of the 3-hour stimulation protocol. Group 1: LL-BRS prolonged AERP from 150 ± 5 to 172 ± 19 milliseconds (P < 0.001). After 3 hours of LL-BRS, NTP-induced AERP-shortening was diminished from -51 ± 10 milliseconds (-34%) to -22 ± 4 milliseconds (-13%) (P < 0.01). AF-inducibility during NTP maneuvers decreased from 90% at baseline to 15% (P < 0.01). Group 2: HL-BRS shortened AERP from 150 ± 17 to 132 ± 8 milliseconds (P = 0.024). After 3 hours of HL-BRS, NTP-induced AERP-shortening was increased from -55 ± 7 milliseconds (-36%) to -72 ± 11 milliseconds (-54%) (P < 0.05) and AF-inducibility was not affected. NTP-induced changes in blood gases and blood pressure were not different between the groups. CONCLUSION: LL-BRS suppressed NTP-induced AERP-shortening and AF-inducibility. By contrast HL-BRS further perpetuated NTP-induced AERP-shortening and increased AF-inducibility. These findings support only the use of LL-BRS as a novel therapeutic modality to treat AF in OSA.

Renal denervation for the treatment of cardiovascular high risk-hypertension or beyond?

Hypertension imposes a major burden of morbidity and mortality and is associated with sympathetic nervous system overactivity. Renal sympathetic denervation has been shown to reduce office blood pressure, ambulatory blood pressure, and sympathetic activity in patients with resistant hypertension. Therefore, the procedure has attracted a lot of attention. Beyond blood pressure, renal denervation has been shown to improve glucose tolerance, microalbuminuria, and arrhythmias in several experimental models and, in admittedly, often uncontrolled clinical studies. It has been demonstrated to reduce myocardial hypertrophy in a blood pressure-independent and blood pressure-dependent way. The first studies on heart failure with preserved and reduced ejection fraction are ongoing. Renal sympathetic denervation holds promise for future indications in hypertension and related comorbidities and consequences, such as metabolic disease, renal failure, and heart failure. Published data in a placebo-control blinded study, however, are needed. The aim of this review is to provide a critical and comprehensive overview of heretofore generated data on renal denervation in experimental models, in human hypertension, and on early developments in new indications, which should indicate the way to powered and performed, controlled clinical studies appropriately.

Obstructive respiratory events and premature atrial contractions after cardioversion.

Recurrence of atrial fibrillation (AF) after electrical cardioversion (ECV) is increased in patients with obstructive sleep apnoea (OSA). In patients with persistent AF, with (n=40) and without (n=32) obstructive respiratory events (OREs) during sedation for ECV, we determined the occurrence of premature atrial contractions (PACs) before and after insertion of a nasopharyngeal tube. The influence of acute obstructive respiratory events on atrial electrophysiology after termination of AF was studied in pigs. Incidence of PACs directly after ECV was higher in patients with OREs compared to those without OREs (7±2 versus 1±1 per 10 s, respectively; p<0.01). Occurrence of PACs could be reduced by 79% by insertion of a nasopharyngeal tube. In a subsequent sleeping study, patients with OREs had higher apnoea-hypopnoea indices and more PACs during night. 16 patient with and four patients without OREs had a relapse of AF during 1 week after ECV (p<0.01). In pigs, acute OREs after 30 min of AF increased occurrence of PACs and vulnerability for reinduction of AF, which could be attenuated by atropine, beta-blockers and renal denervation. OREs are associated with increased occurrence of PACs and more early relapse of AF. OREs increase occurrence of PACs and vulnerability for reinduction of AF by sympathovagal imbalance.

Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension.

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. METHODS AND RESULTS: A total of 346 uncontrolled hypertensive patients, separated according to daytime ambulatory BP monitoring into 303 with true resistant (office systolic BP [SBP] 172.2±22 mm Hg; 24-hour SBP 154±16.2 mm Hg) and 43 with pseudoresistant hypertension (office SBP 161.2±20.3 mm Hg; 24-hour SBP 121.1±19.6 mm Hg), from 10 centers were studied. At 3, 6, and 12 months follow-up, office SBP was reduced by 21.5/23.7/27.3 mm Hg, office diastolic BP by 8.9/9.5/11.7 mm Hg, and pulse pressure by 13.4/14.2/14.9 mm Hg (n=245/236/90; P for all <0.001), respectively. In patients with true treatment resistance there was a significant reduction with RDN in 24-hour SBP (-10.1/-10.2/-11.7 mm Hg, P<0.001), diastolic BP (-4.8/-4.9/-7.4 mm Hg, P<0.001), maximum SBP (-11.7/-10.0/-6.1 mm Hg, P<0.001) and minimum SBP (-6.0/-9.4/-13.1 mm Hg, P<0.001) at 3, 6, and 12 months, respectively. There was no effect on ambulatory BP monitoring in pseudoresistant patients, whereas office BP was reduced to a similar extent. RDN was equally effective in reducing BP in different subgroups of patients. Office SBP at baseline was the only independent correlate of BP response. CONCLUSIONS: RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.

Novel and nonpharmacologic approaches to cardio-protection in hypertension.

Hypertension has wide (30-45 %) prevalence in the general population and is related to important increases in overall cardiovascular morbidity and mortality. Despite lifestyle modifications and optimal medical therapy (three drugs, one being diuretic), about 5-20 % of hypertensives are affected by resistant hypertension. Chronic high blood pressure has adverse effects on the heart and other organs such as the kidneys and vasculature. Renal sympathetic denervation and baroreceptor stimulation are invasive approaches initially investigated to treat resistant hypertension. Their pleiotropic effects appear promising in cardiovascular remodeling, heart failure and arrhythmias and could potentially affect cardiovascular morbidity and mortality.

Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes.

BACKGROUND: Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce. AIMS: This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension. METHODS: This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years. RESULTS: Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up. CONCLUSION: Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension.

Impact of the COVID-19 pandemic on hospital admission rates for arterial hypertension and coronary heart disease: a German database study.

Background: During the SARS-CoV-2 pandemic it was speculated that the virus might be associated with a persistent increase of cardiovascular risk. The present study compares pre- and post-pandemic hospital admission rates for hypertension and coronary artery disease. Methods: Systematic multicentric retrospective cohort analysis of 57.795 hospital admissions in an urban region in Germany during two different periods (pre-pandemic 01-06/2019 vs. post-pandemic era 01-06/2023). Information on hospital admissions for arterial hypertension, chronic coronary syndrome, unstable angina pectoris and acute myocardial infarction were extracted from the hospitals data systems. Additionally, six comorbidities and performed coronary interventions were monitored. Results: Compared to the pre-pandemic era, there was no increase in hospitalizations for arterial hypertension (516 vs. 483, -6.8%, p = 0.07) or myocardial infarction (487 vs. 349, -23.8%, p < 0.001), but the total number of patient admissions with chest pain as the presenting symptom increased (chronic coronary syndrome: 759 vs. 943, +24.2%, p < 0.001; unstable angina pectoris: 270 vs. 451, +67.0%, p < 0.001). At the same time, the number of performed coronary angiographies increased, but less patients underwent percutaneous interventions. Patients admitted with chest pain in the post-pandemic era were in general healthier with less comorbidities. Conclusion: The present multicenter cohort study found no evidence for an increase in hospitalizations for arterial hypertension or coronary artery disease after the end of the pandemic. However, further studies with larger sample sizes are needed to confirm our results.

Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation: SYMPLICITY-AF.

BACKGROUND: The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood. OBJECTIVES: The purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI). METHODS: This study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. RESULTS: A total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by -17.8 ± 12.8 mm Hg and -13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. CONCLUSIONS: In patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.

Effects of electrical stimulation of carotid baroreflex and renal denervation on atrial electrophysiology.

INTRODUCTION: This study was designed to compare the effect of electrical baroreflex stimulation (BRS) at an intensity used in hypertensive patients and renal denervation (RDN) on atrial electrophysiology. BRS and RDN reduce blood pressure and global sympathetic drive in patients with resistant hypertension. Whereas RDN decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive, BRS modulates autonomic balance by activation of the baroreflex, resulting in both reduced sympathetic drive and increased vagal activation. Increased vagal tone potentially shortens atrial refractoriness resulting in a stabilization of reentry circuits perpetuating atrial fibrillation (AF). METHODS AND RESULTS: In normotensive anesthetized pigs (n = 12), we compared the acute effect of BRS and RDN on blood pressure, atrial effective refractory period (AERP), and inducibility of AF. Electrical BRS was titrated to result in comparable heart rate and blood pressure reduction compared to irreversible RDN. BRS resulted in a rapid and pronounced shortening of AERP (from 162 ± 8 milliseconds to 117 ± 16 milliseconds, P = 0.001) associated with increased AF-inducibility from 0% to 82%. This shortening in AERP was completely reversible after stopping BRS. After administration of atropine, AF-inducibility during BRS was attenuated. Ventricular repolarization was not modulated by BRS. In RDN, AF was not inducible; however, it did not prevent BRS-induced shortening of AERP. CONCLUSION: RDN and BRS resulting in comparable blood pressure and heart rate reductions differently influence atrial electrophysiology. Vagally mediated shortening of AERP, resulting in increased AF-inducibility, was observed with BRS but not with RDN.