Cryoablation of stellate ganglia and atrial arrhythmia in ambulatory dogs with pacing-induced heart failure

Background: Occasionally patients with congenitally corrected transposition of the great arteries (ccTGA) exhibit little clinical evidence of cardiovascular limitation even to their 8th decade. We aimed to assess survival prospects in a large cohort of ccTGA adults. Methods & Results: We included 555 ccTGA adults (median age 33.0 years, 48.3% female) under regular follow-up at 28 institutions between 2002 and 2019. The primary outcome was a composite of death, mechanical circulatory support (MCS) and heart transplant. During a median follow-up of 8.1 [IQR 4.4 - 13.3] years, 56 (10.1%) patients died, 10 (1.8%) patients underwent MCS and 14 (2.5%) had a heart transplant. Median age at time of primary outcome was 51.1 [IQR 37.5 - 63.2] years and cumulative incidence at 15 years from baseline was 21.5% [95% CI 16.1 - 26.5]. Leading causes of death were worsening of heart failure (43%) and sudden death (10%). Patients who died were more likely to use heart failure (HF) medications. In multivariable Cox analyses for baseline variables, age, prior atrial arrhythmia and HF admission were each associated with an increased risk of the primary outcome. Figure shows cumulative incidence according to history of atrial arrhythmia. During follow-up, 91 (16.4%) were admitted for HF, pacemaker implantation was performed in 68 (12.3%) patients, ICD in 82 (14.7%), and major cardiac surgery (mostly for systemic AV-valve) in 89 (15.8%) patients. Conclusion: In this large cohort of ccTGA adults, survival seemed to be primarily determined by heart failure-related complications. Prior atrial arrhythmia also seems to be a harbinger for adverse outcome. Few patients underwent advanced HF therapies. Figure: Cumulative incidence of the composite primary outcome (MCS, heart transplant or death) over a period of 14 years from first visit at an adult congenital heart disease clinic since 2002 stratified according to history of atrial arrhythmia. Shading represents upper and lower 95% confidence limits.

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Friedreich’s ataxia-associated childhood hypertrophic cardiomyopathy: a national cohort study

Archives of Disease in Childhood ◽

10.1136/archdischild-2021-322455 ◽

2021 ◽

pp. archdischild-2021-322455

Author(s):

Gabrielle Norrish ◽

Thomas Rance ◽

Elena Montanes ◽

Ella Field ◽

Elspeth Brown ◽

...

Keyword(s):

Heart Failure ◽

Cohort Study ◽

Hypertrophic Cardiomyopathy ◽

Cardiac Death ◽

Friedreich’S Ataxia ◽

Left Ventricular ◽

Friedreich's Ataxia ◽

Atrial Arrhythmia ◽

Primary Study

ObjectiveHypertrophic cardiomyopathy (HCM) is an important predictor of long-term outcomes in Friedreich’s ataxia (FA), but the clinical spectrum and survival in childhood is poorly described. This study aimed to describe the clinical characteristics of children with FA-HCM.Design and settingRetrospective, longitudinal cohort study of children with FA-HCM from the UK.Patients78 children (<18 years) with FA-HCM diagnosed over four decades.InterventionAnonymised retrospective demographic and clinical data were collected from baseline evaluation and follow-up.Main outcome measuresThe primary study end-point was all-cause mortality (sudden cardiac death, atrial arrhythmia-related death, heart failure-related death, non-cardiac death) or cardiac transplantation.ResultsThe mean age at diagnosis of FA-HCM was 10.9 (±3.1) years. Diagnosis was within 1 year of cardiac referral in 34 (65.0%) patients, but preceded the diagnosis of FA in 4 (5.3%). At baseline, 65 (90.3%) had concentric left ventricular hypertrophy and 6 (12.5%) had systolic impairment. Over a median follow-up of 5.1 years (IQR 2.4–7.3), 8 (10.5%) had documented supraventricular arrhythmias and 8 (10.5%) died (atrial arrhythmia-related n=2; heart failure-related n=1; non-cardiac n=2; or unknown cause n=3), but there were no sudden cardiac deaths. Freedom from death or transplantation at 10 years was 80.8% (95% CI 62.5 to 90.8).ConclusionsThis is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly.

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Healthcare utilization after cryoballoon ablation for treatment of atrial fibrillation in patients with heart failure: real-world results from the Cryo AF Global Registry

EP Europace ◽

10.1093/europace/euab116.074 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

R Rordorf ◽

F Scazzuso ◽

KRJ Chun ◽

S Kaur Khelae ◽

FJ Kueffer ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Healthcare Utilization ◽

Real World ◽

Nyha Class ◽

Atrial Arrhythmia ◽

Class I ◽

Left Ventricular Ejection ◽

Cryoballoon Ablation ◽

Global Registry

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic, Inc. OnBehalf Cryo AF Global Registry Investigators Background Heart failure (HF) concomitant to atrial fibrillation (AF) can exacerbate the risk of hospitalization, morbidity, mortality, and impairment in quality of life posed by each condition alone. While the reciprocal relationship between HF and AF challenges effective treatment for these patients, catheter ablation for treatment of AF is reasonable for select patients with AF and HF according to guidelines. Purpose: Assess real-world usage and healthcare utilization outcomes of cryoablation for patients with AF and HF. Methods: The Cryo AF Global Registry (NCT02752737) is an ongoing, prospective, multicenter registry. Patients with AF were enrolled and treated with cryoballoon ablation (Arctic Front Advance, Medtronic) according to clinical practice at 56 sites in 26 countries world-wide. Subjects with NYHA class I-III at baseline comprised the HF cohort and were compared to patients without HF (No-HF). Freedom from atrial arrhythmia recurrence ≥30 sec, adverse events associated with the AF ablation procedure, repeat ablations, AAD usage, and cardiovascular rehospitalization over a 12-month follow-up were compared between cohorts. Results: A total of 1,303 patients (318 HF, 985 No-HF) were included. The HF cohort included patients with NYHA Class I (56.3%) and II/III (43.7%) with either preserved (81.6%) or mid/reduced (18.4%) left ventricular ejection fraction. HF patients were more often female (45.6% vs 33.6%) with persistent AF (25.8% vs 14.3%), larger left atrial diameter (4.4 ± 0.9 vs 4.0 ± 0.7 cm), and higher rates of hypertension (67.9% vs 49.1%) and prior myocardial infarction (3.8% vs 1.7%; all, P < 0.05). The rate of serious procedure-related complications was 5.3% in HF and 3.0% in No-HF (P = 0.08). Freedom from atrial arrhythmia recurrence at 12-months was not different between HF and No-HF patients with either paroxysmal (84.2% (95% CI:78.6-88.4) vs 86.8% (95% CI: 84.2 – 89.0)) or persistent AF (69.6% (95% CI: 58.1 – 78.5) vs 71.8% (95% CI: 63.2-78.7)), respectively (p = 0.32, HF vs No-HF). AF-related symptoms and antiarrhythmic drug use were significantly reduced after cryoablation in the HF and No-HF cohorts (P < 0.05). Freedom from repeat ablation at 12-months was similar between HF and No-HF patients. Of patients who had a cardiovascular rehospitalization after cryoablation, 78% presented with a supraventricular tachyarrhythmia. Persistent AF and HF at baseline both increased the risk of cardiovascular rehospitalization after cryoballoon ablation (P < 0.05). Conclusion: Cryoablation is used to treat patients with AF and concomitant HF in real-world practice and is similarly safe and effective at 12-months in patients with and without HF.

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Abstract 389: Human Cardiac Sympathetic Nerves Switch the Neurotransmitter Property from Catecholaminergic to Cholinergic in Patients with Severe Heart Failure

Circulation ◽

10.1161/circ.118.suppl_18.s_297 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Hideaki Kanazawa ◽

Masaki Ieda ◽

Kensuke Kimura ◽

Takahide Arai ◽

Haruko Manabe ◽

...

Keyword(s):

Heart Failure ◽

Interstitial Fibrosis ◽

Severe Heart Failure ◽

Sympathetic Nerves ◽

Cholinergic Neuron ◽

Heart Weight ◽

Control Group ◽

Down Regulation ◽

Stellate Ganglia ◽

Nerve Bundles

[Background] Congestive heart failure (CHF) is characterized by activation of the sympathetic nervous system (SNS) with depletion of norepinephrine (NE) stores, which was initially considered to be the result of excess NE secretion and the loss of noradrenergic nerve terminals. Recent studies however have revealed that it is caused by down regulation of NE synthesis and re-uptake, although the molecular mechanism of down regulation of the sympathetic neuronal function remains unknown. We recently found in an animal model of CHF that the cardiac SNS switches the neurotransmitter property from catecholaminergic to cholinergic, mediated by cytokines LIF and CT-1 secreted from failing myocardium. This study was designed to investigate whether or not this cholinergic transdifferentiation of cardiac SNS occurs in patients with CHF. [Methods & Results] (1) We analyzed 8 samples from patients who died of non-cardiac causes obtained at autopsy (control group), and 8 samples from patients with CHF (CHF group). Five of them died of CHF, and 3 were obtained from native hearts of transplant recipients. (2) The heart weight was significantly higher in the CHF group. (3) The gross morphology of the cardiac SNS did not differ between the two groups. HE and Masson trichrome staining showed disorganized cardiomyocytes and interstitial fibrosis in CHF. (4) Immunostaining for tyrosine hydroxylase (TH, sympathetic nerve marker) revealed that the epicardial nerve bundles and stellate ganglia of the control group had a predominance of TH + nerves, whereas those of CHF group were significantly decreased. (5) Immunostaining for choline transporter (CHT, cholinergic neuron marker) revealed that CHT + neurons were markedly increased in the epicardial nerve bundles of CHF hearts compared with the control group. Some nerves co-expressed both TH and CHT markers. (6) Immunostaining for choline acetyl transferase (ChAT, a cholinergic neuron marker) revealed that stellate ganglia had a lot of ChAT + neurons compared with the control. (7) Nissl staining showed that there was no difference between the two groups in neuron number in the stellate ganglia. [Conclusions] These results indicated that in patients with CHF the cardiac sympathetic nerves also had cholinergic nerve properties.

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Cryoballoon Ablation for the Treatment of Atrial Fibrillation in Patients With Concomitant Heart Failure and Either Reduced or Preserved Left Ventricular Ejection Fraction: Results From the Cryo AF Global Registry

Journal of the American Heart Association ◽

10.1161/jaha.121.021323 ◽

2021 ◽

Author(s):

Roberto Rordorf ◽

Fernando Scazzuso ◽

Kyoung Ryul Julian Chun ◽

Surinder Kaur Khelae ◽

Fred J. Kueffer ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Left Ventricular Ejection Fraction ◽

Ejection Fraction ◽

Left Ventricular ◽

Atrial Arrhythmia ◽

Left Ventricular Ejection ◽

Cryoballoon Ablation ◽

Ventricular Ejection Fraction ◽

Global Registry

Background Heart failure (HF) and atrial fibrillation (AF) often coexist; yet, outcomes of ablation in patients with AF and concomitant HF are limited. This analysis assessed outcomes of cryoablation in patients with AF and HF. Methods and Results The Cryo AF Global Registry is a prospective, multicenter registry of patients with AF who were treated with cryoballoon ablation according to routine practice at 56 sites in 26 countries. Patients with baseline New York Heart Association class I to III (HF cohort) were compared with patients without HF. Freedom from atrial arrhythmia recurrence ≥30 seconds, safety, and health care utilization over 12‐month follow‐up were analyzed. A total of 1303 patients (318 HF) were included. Patients with HF commonly had preserved left ventricular ejection fraction (81.6%), were more often women (45.6% versus 33.6%) with persistent AF (25.8% versus 14.3%), and had a larger left atrial diameter (4.4±0.9 versus 4.0±0.7 cm). Serious procedure‐related complications occurred in 4.1% of patients with HF and 2.6% of patients without HF ( P =0.188). Freedom from atrial arrhythmia recurrence was not different between cohorts with either paroxysmal AF (84.2% [95% CI, 78.6–88.4] versus 86.8% [95% CI, 84.2–89.0]) or persistent AF (69.6% [95% CI, 58.1–78.5] versus 71.8% [95% CI, 63.2–78.7]) ( P =0.319). After ablation, a reduction in AF‐related symptoms and antiarrhythmic drug use was observed in both cohorts (HF and no‐HF), and freedom from repeat ablation was not different between cohorts. Persistent AF and HF predicted a post‐ablation cardiovascular rehospitalization ( P =0.032 and P =0.001, respectively). Conclusions Cryoablation to treat patients with AF is similarly effective at 12 months in patients with and without HF. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02752737.

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Sympathomodulation in heart failure: A role for stellate ganglia Nrf2

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.564.5 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Julia Shanks ◽

Lie Gao ◽

Irving H. Zucker

Keyword(s):

Heart Failure ◽

Stellate Ganglia

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Sinus node disease: pathophysiology and natural history

ESC CardioMed ◽

10.1093/med/9780198784906.003.0448 ◽

2018 ◽

pp. 1945-1949

Author(s):

Jonathan M. Kalman ◽

Gwilym M. Morris

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Natural History ◽

Sinus Node ◽

Pacemaker Implantation ◽

Atrial Arrhythmia ◽

Current Understanding ◽

Exercise Limitation ◽

Node Disease ◽

Sinus Node Disease

Sinus node disease is the commonest bradyarrhythmia, often presenting as syncope or exercise limitation and is an important reason for pacemaker implantation. It is usually idiopathic and a disease of ageing with a peak incidence in the seventh decade of life, but may develop secondary to other conditions including heart failure and chronic endurance exercise. The detailed pathophysiology of sinus node disease remains unknown, studies have found evidence of widespread atrial electrical remodelling, and contemporary research suggests that cellular electrical and fibrotic changes may be important mediators of this remodelling. There is an important association between sinus node disease and atrial fibrillation, and the two arrhythmias often coexist, but the nature of this interaction remains a source of debate. This chapter will summarize the current understanding of the natural history and pathophysiology of sinus node disease, with a focus on remodelling and including discussion of theories that may explain the development of coexistent atrial arrhythmia in these patients.

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Anti ‐inflammatory Treatment with a Prodrug of Dexamethasone in Stellate Ganglia Attenuates Ventricular Arrhythmogenesis in Chronic Heart Failure Rats

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.564.1 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Dongze Zhang ◽

Huiyin Tu ◽

Dong Wang ◽

Michael C. Wadman ◽

Yulong Li

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Stellate Ganglia ◽

Anti Inflammatory ◽

Ventricular Arrhythmogenesis

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Impact of the Covid-19 related lockdown on physical activity, heart rate and arrhythmia burden in a large prospective cohort of CHF patients

EP Europace ◽

10.1093/europace/euab116.471 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

J Schmitt ◽

J De Sousa ◽

A Bulava ◽

G Golovchiner ◽

R Hatala ◽

...

Keyword(s):

Physical Activity ◽

Heart Failure ◽

Heart Rate ◽

Social Stress ◽

Biventricular Pacing ◽

Atrial Arrhythmia ◽

Cardiac Resynchronization ◽

Private Company ◽

The Impact ◽

Mean Heart Rate

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): BIOTRONIK SE & Co. KG OnBehalf BIO|STREAM.HF Background At the beginning of the Covid-19 pandemic in spring 2020, governments around the world issued curfews and other stay at home orders (‘lockdown’) to limit the spread of the SARS-CoV19 virus. This may have forced people to decrease their physical activity. Physical inactivity as well as social stress is known to be especially deleterious for heart failure (HF) patients. The BIO|STREAM.HF study enrolled such HF patients into a prospective registry with Home Monitoring. Purpose We aimed to evaluate the impact of the lockdown during the first Covid-19 pandemic wave on physical activity and arrhythmia burden of heart failure patients. Methods We analysed daily transmitted data of patients enrolled into a large international registry (BIO|STREAM.HF) being implanted with a cardiac resynchronization therapy (CRT) devices. Patients with NYHA ≥ II and LVEF ≤ 40% before CRT implantation were selected. Intra-individual weekly mean and median values were calculated for the following daily transmitted parameters: physical activity (measured as % of the day during which the patient moves), atrial arrhythmia burden, mean heart rate (at rest), PP variability, PVC burden, and rate of biventricular pacing. Values were calculated for 12 weeks before and 12 weeks after the country-specific effective date of most rigorous restrictions in spring 2020 to visualize the general trend of parameter changes. Moreover, values for intra-individual changes between three 28-days periods (before, during, and after the lockdown) were calculated. Results Of 444 patients, 76% were male. They had a mean age of 69 ± 10 years and LVEF of 28.2 ± 6.7%. HF was of ischemic etiology in 42% of cases and they were in NYHA class II (47.5%), III (50.0%) or IV (2.5%). On average, patients were active for 9% of the day (2 h 10 min). The physical activity decreased by approx. 10% with the onset of the lockdown (figure 1) and recovered within the following eight weeks. Comparison of the 28-days periods before, during and after the lockdown showed a statistically significant intra-individual decrease in physical activity (mean decrease 9 min per day) during the lockdown compared to pre- and post-lockdown values and a trend toward reduced mean heart rates. In parallel, a significant increase in device detected atrial arrhythmia burden (mean increase 17 min per day) was observed. All other parameters did not change significantly. Conclusion Our results show that patients reduced their physical activity during the Covid-19 related lockdown in spring 2020. This was associated with an increase in atrial arrhythmia burden and a reduction of the mean heart rate. Prognostic implications of these results will further be analysed. Abstract Figure.

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