The Impact of Atrial Fibrillation on Clinical Outcomes in Heart Failure with Mid-range and Preserved Ejection Fraction Patients.

BACKGROUND: The combined effect of left ventricular ejection fraction (LVEF) and atrial fibrillation (AF) on clinical outcomes in heart failure (HF) remains complex. OBJECTIVE: In this post-hoc analysis of the TOPCAT trial, we aimed to evaluate the impact of AF on clinical outcomes in patients with HF patients stratified by LVEF range. METHODS: A total of 3442 patients were included, stratified into three groups according to LVEF range: 1) HF with mid-range EF (HFmrEF) - LVEF 45-50% (n=823); 2) HF with preserved LVEF (HFpEF) - LVEF 51-60% (n=1682); 3) HF with normal LVEF (HFnEF) - LVEF >60 % (n=937) and subdivided according to the presence of AF at enrollment. Cox regression analysis was used to define independent associations between AF and clinical outcomes. RESULTS: AF was prevalent in 38.6% in HFmrEF, 34.6% in HFpEF, and 33.7% in HFnEF (p=0.07). In each subgroup, AF was associated with worse primary outcome and HF hospitalizations, and worse cardiovascular mortality in HFpEF and HFnEF. The hazard ratio (HR) for the primary outcome in those with AF compared to sinus rhythm (SR) was 1.11 (1.01-1.22, p=0.03) in HFmrEF; 1.20 (1.11-1.28, p<0.001) in HFpEF; and 1.16 (1.05-1.28, p=0.004) in HFnEF. When LVEF was treated as a continuous variable, there was a linear negative association between LVEF and the effect of AF vs. SR for the primary endpoint and HF hospitalizations and a linear positive association for cardiovascular mortality. CONCLUSION: Compared to SR, AF was independently associated with worse outcomes across all LVEF ranges.

Association between atrial fibrillation and heart failure patient reported outcomes across the ejection fraction spectrum.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS: This is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group). RESULTS: In TOPCAT, among 1,710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI -7.21: -0.74) at 48 months, with a significant AF status by time interaction (P = .03). In HF-ACTION, among 1,814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI -6.21: -1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score. CONCLUSION: Ιn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.

Atrial Myopathy and Ischemic Stroke in Heart Failure With Preserved Ejection Fraction.

Recent studies suggested an association between atrial myopathy and stroke independent of atrial fibrillation (AF). We examined the hypothesis that atrial myopathy may be associated with ischemic stroke in patients with heart failure with preserved ejection fraction. This is an exploratory, post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Patients with sinus rhythm documented at baseline electrocardiogram and without known AF were included in this analysis. Atrial myopathy was defined by echocardiographic evidence of left atrial (LA) enlargement (LA diameter >46 mm or LA volume index >36 ml/m2) or elevated natriuretic peptides (brain natriuretic peptide >100 pg/ml or N-terminal Pro-B-type natriuretic peptide >400 pg/ml). We used Cox regression to investigate the effect of atrial myopathy on incident ischemic stroke over the study period. In 3,445 patients in the TOPCAT trial, 2,225 (mean age 67.5 ± 4.9 years; female 54.8%) had normal sinus rhythm at baseline and no history of AF. Atrial myopathy was present in 756 patients (34.0%). During a median follow-up of 2 years, 56 patients (2.5%) developed ischemic stroke, including 25 with atrial myopathy. Atrial myopathy was associated with increased risk of stroke (hazard ratio = 1.74, 95% confidence interval 1.01 to 2.98, p = 0.04) in multivariate analysis. Diabetes mellitus (hazard ratio = 2.02, 95% confidence interval 1.19 to 3.43 p = 0.01) was the only other independent predictor of stroke. In patients with heart failure with preserved ejection fraction, atrial myopathy increases the risk of ischemic stroke, in the absence of AF. Further investigations are needed to better characterize this association and implement stroke prevention strategies.

Obesity associated with improved mortality of extracorporeal membrane oxygenation for severe COVID-19 pneumonia.

INTRODUCTION: Determining a patient's candidacy for extracorporeal membrane oxygenation (ECMO) in severe COVID-19 pneumonia is a critical aspect of efficient healthcare delivery. A body mass index (BMI) ≥40 is considered a relative contraindication for ECMO by the Extracorporeal Life Support Organization (ELSO). We sought to determine the impact of obesity on the survival of patients with COVID-19 on ECMO. METHODS: This project was a retrospective review of a multicenter US database from January 2020 to December 2021. The primary outcome was in-hospital mortality after ECMO initiation, with a comparison between patients classified into body mass index categories (<30, 30-39.9, and ≥40). Secondary outcomes included ventilator days, intensive care days, and complications. RESULTS: We completed records review on 359 patients, with 90 patients excluded because of missing data. The overall mortality for the 269 patients was 37.5%. Patients with a BMI <30 had higher odds of mortality compared to all patients with BMI >30 (OR 1.98; p = 0.013), those with BMI 30-39.9 (OR 1.84; p = 0.036), and BMI ≥40 (OR 2.33; p = 0.024). There were no differences between BMI groups for ECMO duration; length of stay (LOS); or rate of bloodstream infection, stroke, or blood transfusion. Age, ECMO duration, and modified-Elixhauser index were not independent risk factors for mortality. CONCLUSIONS: In patients receiving ECMO for severe COVID-19, neither obesity (BMI >30) nor morbid obesity (BMI >40) were associated with in-hospital mortality. These results are consistent with previous reports and held true after adjusting for age and comorbidities. Our data suggest further examination of the recommendations to withhold ECMO in patients who are obese.

Transcutaneous Vagus Nerve Stimulation Ameliorates the Phenotype of Heart Failure With Preserved Ejection Fraction Through Its Anti-Inflammatory Effects.

BACKGROUND: A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction (HFpEF). Low-level transcutaneous vagus nerve stimulation (LLTS) suppresses inflammation in animals and humans, mediated by an α7nAchR (alpha7 nicotinic acetylcholine receptor)-dependent pathway. We examined the effects of LLTS on cardiac function, inflammation, and fibrosis in the presence of α7nAchR pharmacological blockade in a rat model of HFpEF. METHODS: Dahl salt-sensitive rats at 7 weeks of age were treated with high-salt diet for 6 weeks to induce HFpEF, followed by 4 weeks of (1) LLTS, (2) LLTS with the α7nAchR blocker methyllycaconitine, (3) sham, and (4) olmesartan. Blood pressure, cardiac function by echocardiography, heart rate variability, and serum cytokines were measured at 13 and 17 weeks of age. Cardiac fibrosis, inflammatory cell infiltration, and gene expression were determined at 17 weeks. RESULTS: LLTS attenuated the increase in blood pressure; improved cardiac function; decreased inflammatory cytokines, macrophage infiltration, and fibrosis; and improved survival compared with other groups. Methyllycaconitine attenuated these effects, whereas olmesartan did not improve cardiac function or fibrosis despite maintaining similar blood pressure as LLTS. Heart rate variability was similarly improved in the LLTS and LLTS plus methyllycaconitine groups but remained low in the other groups. LLTS reversed the dysregulated inflammatory signaling pathways in HFpEF hearts. CONCLUSIONS: Neuromodulation with LLTS improved cardiac function in a rat model of HFpEF through its anti-inflammatory and antifibrotic effects. These results provide the basis for further clinical trials in humans.

Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Clinical Trial.

Background A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction. Low-level transcutaneous vagus nerve stimulation suppresses inflammation in humans. We conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low-level transcutaneous vagus nerve stimulation on cardiac function, exercise capacity, and inflammation in patients with heart failure with preserved ejection fraction. Methods and Results Patients with heart failure with preserved ejection fraction and at least 2 additional comorbidities (obesity, diabetes, hypertension, or age ≥65 years) were randomized to either active (tragus) or sham (earlobe) low-level transcutaneous vagus nerve stimulation (20 Hz, 1 mA below discomfort threshold), for 1 hour daily for 3 months. Echocardiography, 6-minute walk test, quality of life, and serum cytokines were assessed at baseline and 3 months. Fifty-two patients (mean age 70.4±9.2 years; 70% female) were included (active, n=26; sham, n=26). Baseline characteristics were balanced between the 2 arms. Adherence to the protocol of daily stimulation was >90% in both arms (P>0.05). While the early mitral inflow Doppler velocity to the early diastolic mitral annulus velocity ratio did not differ between groups, global longitudinal strain and tumor necrosis factor-α levels at 3 months were significantly improved in the active compared with the sham arm (-18.6%±2.5% versus -16.0%±2.4%, P=0.002; 8.9±2.8 pg/mL versus 11.3±2.9 pg/mL, P=0.007, respectively). The reduction in tumor necrosis factor-α levels correlated with global longitudinal strain improvement (r=-0.73, P=0.001). Quality of life was better in the active arm. No device-related side effects were observed. Conclusions Neuromodulation with low-level transcutaneous vagus nerve stimulation over 3 months resulted in a significant improvement in global longitudinal strain, inflammatory cytokines, and quality of life in patients with heart failure with preserved ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03327649.

Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure.

Aims: Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular tachy-arrhythmias, while vagus nerve stimulation has shown promising anti-arrhythmic effects in in vivo and ex vivo animal studies. We aimed to examine the effect of non-invasive, acute low-level tragus stimulation (LLTS) on TWA in patients with ischemic cardiomyopathy and heart failure. Methods: 26 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and chronic stable heart failure, previously implanted with an automatic implantable cardioverter defibrillator (ICD) device with an atrial lead (dual chamber ICD or cardiac resynchronization therapy defibrillator), were enrolled in the study. Each patient sequentially received, (1) Sham LLTS (electrode on tragus, but no stimulation delivered) for 5 min; (2) Active LLTS at two different frequencies (5 and 20 Hz, 15 min each); and (3) Active LLTS, during concomitant atrial pacing at 100 bpm at two different frequencies (5 and 20 Hz, 15 min each). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 µs, frequency 5/20 Hz, amplitude 1 mA lower than the discomfort threshold). TWA burden was assessed using continuous ECG monitoring during sham and active LLTS in sinus rhythm, as well as during atrial pacing. Results: Right atrial pacing at 100 bpm led to significantly heightened TWA burden compared to sinus rhythm, with or without LLTS. Acute LLTS at both 5 and 20 Hz, during sinus rhythm led to a significant rise in TWA burden in the precordial leads (p < 0.05). Conclusion: Acute LLTS results in a heart-rate dependent increase in TWA burden.

Screening for Atrial Fibrillation in American Indian Adults in a Tribal Primary Care Clinic.

Background American Indian adults have a higher risk of atrial fibrillation (AF) compared with other racial groups. We implemented opportunistic screening to detect silent AF in American Indian adults attending a tribal health system using a mobile, single-lead ECG device. Methods and Results American Indian patients aged ≥50 years followed in a tribal primary care clinic with no history of AF underwent a 30-second ECG. A cardiologist overread all tracings to confirm the diagnosis of AF. After AF was confirmed, patients were referred to their primary care physician for initiation of anticoagulation. Patients seen over the same time period, who were not undergoing screening, served as controls. A total of 1019 patients received AF screening (mean age, 61.5±8.9 years, 62% women). Age and sex distribution of those screened was similar to the overall clinic population. New AF was diagnosed in 15 of 1019 (1.5%) patients screened versus 4 of 1267 (0.3%) patients who were not screened (mean difference, 1.2%; 95% CI, 0.3%-2.2%, P=0.002). Eight of 15 with new screen-detected AF were aged <65 years. Those with screen-detected AF were slightly older and had a higher CHA2DS2-VASc score than those without AF. Fourteen of 15 patients diagnosed with new AF had a CHA2DS2-VASc score ≥1 and initiated anticoagulation. Conclusions Opportunistic, mobile single-lead ECG screening for AF is feasible in tribal clinics, and detects more AF than usual care, leading to appropriate initiation of anticoagulation. AF develops at a younger age in American Indian adults who would likely benefit from earlier AF screening. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03740477.

Effect of Obesity on Response to Spironolactone in Patients With Heart Failure With Preserved Ejection Fraction.

Obesity is common in heart failure with preserved ejection fraction (HFpEF). Whether obesity modifies the response to spironolactone in patients with HFpEF remains unclear. We aimed to investigate the effect of obesity, defined by body mass index (BMI) and waist circumference (WC), on response to spironolactone in patients with HFpEF enrolled in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. This was a post-hoc, exploratory analysis of the Americas cohort of Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. BMI≥30 kg/m2 was used to define the obese group and WC≥102 cm in men and ≥88 cm in women were defined as high WC. In separate analyses, BMI and WC were treated as continuous variables. The effect of spironolactone versus placebo on outcomes was calculated by BMI and WC using Cox proportional hazard models. Obese patients were younger and had more co-morbidities. In multivariate analysis, spironolactone use was associated with a significant reduction in the primary end point, compared with placebo in obese [hazard ratio (HR = 0.618, 95% CI 0.460 to 0.831, p = 0.001), but not in nonobese subjects (HR = 0.946, 95% CI 0.623 to 1.437, p = 0.796; p for interaction = 0.056). There was a linear association between continuous BMI and the effect of spironolactone, with the effect becoming significant at 33kg/m2. Similar results were obtained for the WC-based analysis. In conclusion, use of spironolactone in obese patients with HFpEF was associated with a decreased risk of the primary end point, cardiovascular death and HF hospitalizations, compared with placebo. Further prospective randomized studies in obese subjects are required.

Sex differences in the incidence and mode of death in rats with heart failure with preserved ejection fraction.

NEW FINDINGS: What is the central question of this study? Prior studies failed to address the role of sex in modifying the pathophysiology and response to therapy in heart failure with preserved ejection fraction (HFpEF), potentially introducing bias into translational findings. We aimed to explore sex differences in outcomes and sought to identify the underlying mechanisms in a well-established rat model of HFpEF. What is the main finding and its importance? Male rats with HFpEF exhibited worse survival compared with females and were at a higher risk for sudden death, attributable in part to QT prolongation, autonomic dysregulation and enhanced inflammation. These data might provide the basis for the development of sex-specific interventions in HFpEF targeting these abnormalities. ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of heart failure, and sudden death is the leading cause of mortality. We aimed to explore sex differences in outcomes in rats with HFpEF and sought to identify the underlying mechanisms. Dahl salt-sensitive rats of either sex were randomized into high-salt diet (HS diet; 8% NaCl, n = 46, 50% female) or low-salt diet (LS diet; 0.3% NaCl; n = 24, 50% female) at 7 weeks of age. After 6 and 10 weeks of LS or HS diets, the ECG, heart rate variability, cytokines and echocardiographic parameters were measured. The animals were monitored daily for development of HFpEF and survival. Over 6 weeks of HS diet, rats developed significant hypertension and signs of HFpEF. Compared with female HS diet-fed rats, males exhibited more left ventricular dilatation, a longer QT interval, and worse autonomic tone, as assessed by heart rate variability and elevated inflammatory cytokines. Ten of 23 (46%) male rats died during follow-up, compared with two of 23 (9%) female rats (P = 0.01). There were four sudden deaths in males (with ventricular tachycardia documented in one rat), whereas the females died of heart failure. In conclusion, male rats with HFpEF exhibit worse survival compared with females and are at a higher risk for sudden death, attributable in part to QT prolongation, autonomic dysregulation and enhanced inflammation. These data might provide the basis for the development of sex-specific interventions in HFpEF targeting these abnormalities.

Non-invasive vagus nerve stimulation attenuates proinflammatory cytokines and augments antioxidant levels in the brainstem and forebrain regions of Dahl salt sensitive rats.

The anti-inflammatory effects of vagus nerve stimulation are well known. It has recently been shown that low-level, transcutaneous stimulation of vagus nerve at the tragus (LLTS) reduces cardiac inflammation in a rat model of heart failure with preserved ejection fraction (HFpEF). The mechanisms by which LLTS affect the central neural circuits within the brain regions that are important for the regulation of cardiac vagal tone are not clear. Female Dahl salt-sensitive rats were initially fed with either low salt (LS) or high salt (HS) diet for a period of 6 weeks, followed by sham or active stimulation (LLTS) for 30 min daily for 4 weeks. To study the central effects of LLTS, four brainstem (SP5, NAb, NTS, and RVLM) and two forebrain sites (PVN and SFO) were examined. HS diet significantly increased the gene expression of proinflammatory cytokines in the SP5 and SFO. LLTS reversed HS diet-induced changes at both these sites. Furthermore, LLTS augmented the levels of antioxidant Nrf2 in the SP5 and SFO. Taken together, these findings suggest that LLTS has central anti-inflammatory and antioxidant properties that could mediate the neuromodulation of cardiac vagal tone in the rat model of HFpEF.

TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial.

OBJECTIVES: This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF. BACKGROUND: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown. METHODS: LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months. AF burden over 2-week periods was assessed by noninvasive continuous electrocardiogram monitoring at baseline, 3 months, and 6 months. Five-minute electrocardiography and serum were obtained at each visit to measure heart rate variability and inflammatory cytokines, respectively. RESULTS: Baseline characteristics were balanced between the 2 groups. Adherence to the stimulation protocol (≤4 sessions lost per month) was 75% in the active arm and 83% in the control arm (p > 0.05). At 6 months, the median AF burden was 85% lower in the active arm compared with the control arm (ratio of medians: 0.15; 95% confidence interval: 0.03 to 0.65; p = 0.011). Tumor necrosis factor-alpha was significantly decreased by 23% in the active group relative to the control group (ratio of medians: 0.77; 95% confidence interval: 0.63 to 0.94; p = 0.0093). Frequency domain indices of heart rate variability were significantly altered with active versus control stimulation (p < 0.01). No device-related side effects were observed. CONCLUSIONS: Chronic, intermittent LLTS resulted in lower AF burden than did sham control stimulation, supporting its use to treat paroxysmal AF in selected patients. (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation [TREAT-AF]; NCT02548754).

Atrioventricular junctional ablation: The good, the bad, the better.

BACKGROUND: The management of patients with atrial fibrillation and an abnormally fast ventricular response has been through the use of pharmacologic agents. In those cases where rate control cannot be achieved pharmacologically, a standard approach has been atrioventricular (AV) junctional ablation and ventricular pacemaker implantation to achieve a stable ventricular rate. Long-term ventricular pacing has been shown to result in diminished ventricular function that can lead to heart failure. OBJECTIVE: To describe an experimental and clinical study demonstrating a modified form of AV junction ablation. METHODS: Ablation of the slow and fast AV nodal input does not produce AV block. Ablation of the connection between the two induces AV block, leaving the AV node and His bundle intact. RESULTS: Subsequently the escape heart rate is close to normal and responds well to exercise. CONCLUSION: In a clinical study with a 42 month follow-up, the modified procedure resulted in significantly reduced pacemaker dependence and mortality compared to the standard AV ablation procedure.

Percutaneous Coronary Intervention With Drug-Eluting Stent Versus Optimal Medical Therapy for Chronic Total Occlusion: Systematic Review and Meta-Analysis.

The optimal treatment strategy for coronary chronic total occlusion (CTO) has not been well established. The benefit of percutaneous coronary intervention (PCI) was inferred mainly from observational studies comparing successful versus failed PCI without a control group receiving optimal medical therapy (OMT). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing PCI using drug-eluting stent (DES) versus OMT alone in patients with CTO. Eight studies were identified: 3 RCTs and 5 observational studies. Among a total of 4784 included patients, 2461 patients underwent PCI and 2323 patients received OMT. There was a significant association between PCI and lower cardiac mortality (odds ratio = 0.62; 95% confidence interval 0.42-0.93; P = .02). There was no significant difference between PCI and OMT regarding major adverse cardiac events, recurrent myocardial infarction (MI), repeat revascularization, or stroke. In the RCT subset (1399 patients), there was no significant difference between PCI and OMT regarding clinical outcomes. Compared with OMT alone, PCI with DES for CTO was associated with lower cardiac mortality, mainly driven by observational studies, without significant difference in recurrent MI or repeated revascularization. Further RCTs are needed to investigate the role of PCI for management of patients with CTO.

Replicate separation from dead dwarf cells of Stentor coeruleus.

INTRODUCTION: The present studies initially show the induction of dwarf forms from the disrupted cells of the large unicellular organism, Stentor coeruleus. The dwarf cells placed in a toxic solution showed evidence of cell death. Within minutes a morphological replicate of the cell separates and subsequently fades. METHODS: Dehydration of the commercially available Stentor media in deep well slides (n = 9) caused disruption of the large cells. Rehydration with sterile media allowed formation of mobile dwarf forms. The latter (n = 9) placed in a toxic solution lost mobility and showed evidence of cell death, i.e., apoptosis. Deep well slides (n = 9) containing sterile Stentor media were used as controls. RESULTS: In the slides following dehydration/ rehydration of the living Stentor media, 7of 9 showed mobile dwarf cells compared to 0 of 9 with the sterile media alone, p < 0.05). Within 8-12 min, the stationary dwarf cell progressively released a morphological replicate of the dead cell which contained entrapped bacteria. Subsequent fading of the replicate allowed dispersion of the bacteria. CONCLUSION: These findings provide evidence that cell death indicated by apopotosis (blebbing) is followed by a sequence consisting of the progressive separation of a replicate image which is initially visible then becoming a progressively non-visible, faded image.

Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans.

Low-level transcutaneous vagus nerve stimulation at the tragus (LLTS) is anti-adrenergic. We aimed to evaluate the acute effects of LLTS on left ventricular (LV) function and autonomic tone. Patients with diastolic dysfunction and preserved LV ejection fraction were enrolled in a prospective, randomized, double-blind, 2 × 2 cross-over study. Patients received two separate, 1-h sessions, at least 1 day apart, of active LLTS (20 Hz, 1 mA below the discomfort threshold) and sham stimulation. Echocardiography was performed after LLTS or sham stimulation to assess cardiac function. A 5-min ECG was performed to assess heart rate variability (HRV). Twenty-four patients were enrolled. LV global longitudinal strain improved by 1.8 ± 0.9% during active LLTS compared to sham stimulation (p = 0.001). Relative to baseline, HRV frequency domain components (low frequency, high frequency, and their ratio) were favorably altered after LLTS compared to sham stimulation (all p < 0.05). We concluded that LLTS acutely ameliorates cardiac mechanics by modulating the autonomic tone. Trial registration: NCT02983448.

Slow/Fast Atrioventricular Nodal Reentrant Tachycardia Using the Inferolateral Left Atrial Slow Pathway: Role of the Resetting Response to Select the Ablation Target.

Background We describe a technique to localize the ablation target in patients with an unusual variant of slow/fast atrioventricular nodal reentrant tachycardia (AVNRT) using a slow pathway connecting to the basal inferolateral left atrium. Methods Consecutive patients with slow/fast AVNRT were included. During stable slow/fast AVNRT, a single late atrial extrastimulus (AES) was delivered at the inferolateral left atrium near the mitral annulus. Advancing the next His bundle potential by ≥5 ms, followed by resetting of the tachycardia cycle length, indicated that the AES engaged the anterograde slow pathway. The latest AES resetting AVNRT was considered to be in close proximity to the atrial end of the anterograde slow pathway and was selected as the ablation target. Results In 10 of 843 (1.2%) patients, ablation at the inferolateral left atrium was required. All patients had had failed ablation at the inferior triangle of Koch and roof of the coronary sinus. In all 10 patients, a late AES advanced the His bundle potential by ≥10 ms and reset the tachycardia. Ablation at that site eliminated slow pathway conduction and terminated the tachycardia. Ablation was successful at the site of the latest AES, delivered 49±12 ms after the onset of the His bundle potential. No recurrent tachycardia was noted at 1 year of follow-up. Conclusions The inferolateral left atrium slow pathway is used in a small subset of patients with slow/fast AVNRT. Accurate localization of the ablation target can be achieved by delivering late AES during AVNRT (resetting response).