Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias: A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Developing an Echocardiography-Based, Automatic Deep Learning Framework for the Differentiation of Increased Left Ventricular Wall Thickness Etiologies.

AIMS: Increased left ventricular (LV) wall thickness is frequently encountered in transthoracic echocardiography (TTE). While accurate and early diagnosis is clinically important, given the differences in available therapeutic options and prognosis, an extensive workup is often required to establish the diagnosis. We propose the first echo-based, automated deep learning model with a fusion architecture to facilitate the evaluation and diagnosis of increased left ventricular (LV) wall thickness. METHODS AND RESULTS: Patients with an established diagnosis of increased LV wall thickness (hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA), and hypertensive heart disease (HTN)/others) between 1/2015 and 11/2019 at Mayo Clinic Arizona were identified. The cohort was divided into 80%/10%/10% for training, validation, and testing sets, respectively. Six baseline TTE views were used to optimize a pre-trained InceptionResnetV2 model. Each model output was used to train a meta-learner under a fusion architecture. Model performance was assessed by multiclass area under the receiver operating characteristic curve (AUROC). A total of 586 patients were used for the final analysis (194 HCM, 201 CA, and 191 HTN/others). The mean age was 55.0 years, and 57.8% were male. Among the individual view-dependent models, the apical 4-chamber model had the best performance (AUROC: HCM: 0.94, CA: 0.73, and HTN/other: 0.87). The final fusion model outperformed all the view-dependent models (AUROC: HCM: 0.93, CA: 0.90, and HTN/other: 0.92). CONCLUSION: The echo-based InceptionResnetV2 fusion model can accurately classify the main etiologies of increased LV wall thickness and can facilitate the process of diagnosis and workup.

A real-world experience of atrioventricular synchronous pacing with leadless ventricular pacemakers.

AIMS: The MicraTM transcatheter pacing system (TPS) (Medtronic) is the only leadless pacemaker that promotes atrioventricular (AV) synchrony via accelerometer-based atrial sensing. Data regarding the real-world experience with this novel system are scarce. We sought to characterize patients undergoing MicraTM -AV implants, describe percentage AV synchrony achieved, and analyze the causes for suboptimal AV synchrony. METHODS: In this retrospective cohort study, electronic medical records from 56 consecutive patients undergoing MicraTM -AV implants at the Mayo Clinic sites in Minnesota, Florida, and Arizona with a minimum follow-up of 3 months were reviewed. Demographic data, comorbidities, echocardiographic data, and clinical outcomes were compared among patients with and without atrial synchronous ventricular pacing (AsVP) ≥ 70%. RESULTS: Sixty-five percent of patients achieved AsVP ≥ 70%. Patients with adequate AsVP had smaller body mass indices, a lower proportion of congestive heart failure, and prior cardiac surgery. Echocardiographic parameters and procedural characteristics were similar across the two groups. Active device troubleshooting was associated with higher AsVP. The likely reasons for low AsVP were small A4-wave amplitude, high ventricular pacing burden, and inadequate device reprogramming. Importantly, in patients with low AsVP, subjective clinical worsening was not noted during follow-up. CONCLUSION: With the increasing popularity of leadless pacemakers, it is paramount for device implanting teams to be familiar with common predictors of AV synchrony and troubleshooting with MicraTM -AV devices.

Outcomes and periprocedural management of cardiac implantable electronic devices in patients with carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is a rare complication of hormonally active neuroendocrine tumors that often requires surgical intervention. Data on cardiac implantable electronic device (CIED) implantation in patients with CHD are limited. OBJECTIVE: The purpose of this study was to evaluate the experience of CIED implantation in patients with CHD. METHODS: Patients with a diagnosis of CHD and a CIED procedure from January 1, 1995, through June 1, 2020, were identified using a Mayo Clinic proprietary data retrieval tool. Retrospective review was performed to extract relevant data, which included indications for implant, procedural details, complications, and mortality. RESULTS: A total of 27 patients (55.6% male; mean age at device implant 65.6 ± 8.8 years) with cumulative follow-up of 75 patient-years (median 1.1 years; interquartile range 0.4-4.6 years) were included for analysis. The majority of implanted devices were dual-chamber permanent pacemakers (63%). Among all CHD patients who underwent any cardiac surgery, the incidence of CIED implantation was 12%. The most common indication for implantation was high-grade heart block (66.7%). Device implant complication rates were modest (14.8%). No patient suffered carcinoid crisis during implantation, and there was no periimplant mortality. Median time from implant to death was 2.5 years, with 1-year mortality of 15%. CONCLUSION: CHD is a morbid condition, and surgical valve intervention carries associated risks, particularly a high requirement for postoperative pacing needs. Our data suggest that CIED implantation can be performed relatively safely. Clinicians must be aware of the relevant carcinoid physiology and take appropriate precautions to mitigate risks.

Premature ventricular complexes: diagnostic and therapeutic considerations in clinical practice : A state-of-the-art review by the American College of Cardiology Electrophysiology Council.

Premature ventricular complexes (PVCs) are common arrhythmias in the clinical setting. PVCs in the structurally normal heart are usually benign, but in the presence of structural heart disease (SHD), they may indicate increased risk of sudden death. High PVC burden may induce cardiomyopathy and left ventricular (LV) dysfunction or worsen underlying cardiomyopathy. Sometimes PVCs may be a marker of underlying pathophysiologic process such as myocarditis. Identification of PVC burden is important, since cardiomyopathy and LV dysfunction can reverse after catheter ablation or pharmacological suppression. This state-of-the-art review discusses pathophysiology, clinical manifestations, how to differentiate benign and malignant PVCs, PVCs in the structurally normal heart, underlying SHD, diagnostic procedures (physical examination, electrocardiogram, ambulatory monitoring, exercise testing, echocardiography, cardiac magnetic resonance imaging, coronary angiography, electrophysiology study), and treatment (lifestyle modification, electrolyte imbalance, medical, and catheter ablation).

Sudden cardiac arrest and ventricular arrhythmias following first type I myocardial infarction in the contemporary era.

INTRODUCTION: Myocardial infarction (MI) is associated with an increase in subsequent heart failure (HF), recurrent ischemic events, sudden cardiac arrest, and ventricular arrhythmias (SCA-VA). The primary objective of the study to determine the role of intercurrent HF and ischemic events on the development of SCA-VA following first type I MI. METHODS AND RESULTS: A retrospective cohort study of patients experiencing first type 1 MI in Olmsted County, Minnesota (2002-2012) was conducted by identifying patients using the medical records linkage system (Rochester epidemiology project). Patients aged ≥18 years were followed from the time of MI till death or 31 July, 2017. Intercurrent HF and ischemic events were the primary exposures following MI and their association with outcome SCA-VA was assessed. Eight hundred and sixty-seven patients (mean age was 63 ± 14.5 years; 69% male; 49.8% ST-elevation myocardial infarction) who had their first type I MI during the study period were included. Majority of acute MI patients were revascularized using percutaneous coronary intervention and bypass surgery (628 [72.43%] and 87 [10.03%] respectively). During a mean follow-up of 7.69 ± 4.17 years, HF, recurrent ischemic events and SCA-VA occurred in 155 (17.9%), 245 (28.3%), and 40 (4.61%) patients respectively. Low ejection fraction (adjusted hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.93-0.98; P < .001), intercurrent HF (adjusted HR 3.11; 95% CI, 1.39-6.95; P = .006) and recurrent ischemic events (adjusted HR 3.47; 95% CI, 1.68-7.18; P < .001) were associated with subsequent SCA-VA. CONCLUSION: SCA-VA occurred in a small proportion of patients after MI and is associated with intercurrent HF and recurrent ischemic events.

F-box protein-32 down-regulates small-conductance calcium-activated potassium channel 2 in diabetic mouse atria.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation, but the underlying ionic mechanism for this association remains unclear. We recently reported that expression of the small-conductance calcium-activated potassium channel 2 (SK2, encoded by KCCN2) in atria from diabetic mice is significantly down-regulated, resulting in reduced SK currents in atrial myocytes from these mice. We also reported that the level of SK2 mRNA expression is not reduced in DM atria but that the ubiquitin-proteasome system (UPS), a major mechanism of intracellular protein degradation, is activated in vascular smooth muscle cells in DM. This suggests a possible role of the UPS in reduced SK currents. To test this possibility, we examined the role of the UPS in atrial SK2 down-regulation in DM. We found that a muscle-specific E3 ligase, F-box protein 32 (FBXO-32, also called atrogin-1), was significantly up-regulated in diabetic mouse atria. Enhanced FBXO-32 expression in atrial cells significantly reduced SK2 protein expression, and siRNA-mediated FBXO-32 knockdown increased SK2 protein expression. Furthermore, co-transfection of SK2 with FBXO-32 complementary DNA in HEK293 cells significantly reduced SK2 expression, whereas co-transfection with atrogin-1ΔF complementary DNA (a nonfunctional FBXO-32 variant in which the F-box domain is deleted) did not have any effects on SK2. These results indicate that FBXO-32 contributes to SK2 down-regulation and that the F-box domain is essential for FBXO-32 function. In conclusion, DM-induced SK2 channel down-regulation appears to be due to an FBXO-32-dependent increase in UPS-mediated SK2 protein degradation.

Left atrial appendage exclusion during mitral valve surgery and stroke in atrial fibrillation.

PURPOSE: The purpose of this study was to determine whether surgical left atrial appendage (LAA) exclusion performed during mitral valve surgery is associated with a reduction in cerebrovascular events in patients with atrial fibrillation. METHODS: We retrospectively studied patients with atrial fibrillation who underwent mitral valve surgery from 1/1/2001 through 12/31/2014. We screened 1352 patients using ICD-9 codes and included 281 patients in the study. The primary end point was a composite of strokes and transient ischemic attacks occurring within 5 years after surgery. Secondary end points were stroke, transient ischemic attack, and all-cause mortality. RESULTS: The LAA exclusion group (n = 188) had a lower prevalence of female gender, hypertension, and diabetes mellitus compared with the non-LAA exclusion group (n = 93). The CHA2DS2VASc scores were comparable between groups (2.6 vs 2.9, P = .11), as was anticoagulant use (82.4% vs 85.0%, P = .60). Concomitant surgical ablation was performed in 73.9% of patients who underwent LAA exclusion. Nine cerebrovascular events occurred in the LAA exclusion group and 13 in the non-LAA exclusion group (HR 0.30 [0.12-0.75], P = .01). There was no difference in all-cause mortality between groups. On multivariate analysis of the primary end point of strokes or transient ischemic attacks, significant variables were LAA exclusion (HR 0.31 [0.12-0.76], P = .01) and CHA2DS2VASc score (HR 1.44 [1.11-1.87], P = .006). The benefit of LAA exclusion was detected only when performed together with surgical ablation (HR 0.27 [0.09-0.72], P = .01). CONCLUSIONS: LAA exclusion was associated with fewer cerebrovascular events. However, this benefit was seen only with concomitant surgical ablation.

Regulation of vascular large-conductance calcium-activated potassium channels by Nrf2 signalling.

BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-ß1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-ß1. In addition, the muscle ring finger protein 1 (MuRF1), a known E-3 ligase targeting BK-ß1 ubiquitination and proteasomal degradation, was significantly augmented. These findings were reproduced by knockdown of Nrf2 by siRNA in cultured human coronary artery smooth muscle cells. In contrast, adenoviral transfer of Nrf2 gene in these cells downregulated MuRF1 and upregulated BK-ß1 expression. Activation of Nrf2 by dimethyl fumarate preserved BK-ß1 expression and protected BK channel and vascular function in db/db coronary arteries. These results indicate that expression of BK-ß1 is closely regulated by Nrf2 and vascular BK channel function can be restored by Nrf2 activation. Nrf2 should be considered a novel therapeutic target in the treatment of diabetic vasculopathy.

Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society.

The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease is the leading cause of death and major disability in adults ≥75 years of age; however, despite the large impact of cardiovascular disease on quality of life, morbidity, and mortality in older adults, patients aged ≥75 years have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older patients with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in a nursing home or assisted living facility. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older patients typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision making, and recommend future research to close existing knowledge gaps. To achieve these objectives, we conducted a detailed review of current American College of Cardiology/American Heart Association and American Stroke Association guidelines to identify content and recommendations that explicitly targeted older patients. We found that there is a pervasive lack of evidence to guide clinical decision making in older patients with cardiovascular disease, as well as a paucity of data on the impact of diagnostic and therapeutic interventions on key outcomes that are particularly important to older patients, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older patients representative of those seen in clinical practice and that incorporate relevant outcomes important to older patients in the study design. The results of these studies will provide the foundation for future evidence-based guidelines applicable to older patients, thereby enhancing patient-centered evidence-based care of older people with cardiovascular disease in the United States and around the world.

Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society.

The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease is the leading cause of death and major disability in adults ≥75 years of age; however, despite the large impact of cardiovascular disease on quality of life, morbidity, and mortality in older adults, patients aged ≥75 years have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older patients with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in a nursing home or assisted living facility. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older patients typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision making, and recommend future research to close existing knowledge gaps. To achieve these objectives, we conducted a detailed review of current American College of Cardiology/American Heart Association and American Stroke Association guidelines to identify content and recommendations that explicitly targeted older patients. We found that there is a pervasive lack of evidence to guide clinical decision making in older patients with cardiovascular disease, as well as a paucity of data on the impact of diagnostic and therapeutic interventions on key outcomes that are particularly important to older patients, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older patients representative of those seen in clinical practice and that incorporate relevant outcomes important to older patients in the study design. The results of these studies will provide the foundation for future evidence-based guidelines applicable to older patients, thereby enhancing patient-centered evidence-based care of older people with cardiovascular disease in the United States and around the world.

Surgery for Aortic Dilatation in Patients With Bicuspid Aortic Valves: A Statement of Clarification From the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (Circulation. 2010;121:e266-e369) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (Circulation. 2014;129:e521-e643). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline.

Brugada syndrome and its relevance in the perioperative period.

Brugada syndrome is an autosomal dominant genetic disorder associated with an increased risk of sudden cardiac death, as well as ventricular tachyarrhythmias.The defective cardiac sodium channels result in usual electrocardiographic findings of a coved-type ST elevation in precordial leads V1 to V3. The majority of patients have uncomplicated courses with anesthesia, surgery, and invasive procedures. However there is risk of worsening ST elevation and ventricular arrhythmias due to perioperative medications, surgical insult, electrolyte abnormalities, fever, autonomic nervous system tone, as well as other perturbations. Given the increasing numbers of patients with inherited conduction disorders presenting for non-cardiac surgery that are at risk of sudden cardiac death, safe anesthetic management depends upon a detailed knowledge of these conditions.

Ventilatory gas exchange and early response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an accepted intervention for chronic heart failure (HF), although approximately 30% of patients are non-responders. The purpose of this study was to determine whether exercise respiratory gas exchange obtained before CRT implantation predicts early response to CRT. METHODS: Before CRT implantation, patients were assigned to either a mild-moderate group (Mod G, n = 33, age 67 ± 10 years) or a moderate-severe group (Sev G, n = 31, age 67 ± 10 years), based on abnormalities in exercise gas exchange. Severity of impaired gas exchange was based on a score from the measures of VE/VCO(2) slope, resting PETCO(2) and change of PETCO(2) from resting to peak. All measurements were performed before and 3 to 4 months after CRT implantation. RESULTS: Although Mod G did not have improved gas exchange (p > 0.05), Sev G improved significantly (p < 0.05) post-CRT. In addition, Mod G did not show improved right ventricular systolic pressure (RSVP; pre vs post: 37 ± 14 vs 36 ± 11 mm Hg, p > 0.05), yet Sev G showed significantly improved RVSP, by 23% (50 ± 14 vs 42 ± 12 mm Hg, p < 0.05). Both groups had improved left ventricular ejection fraction (p < 0.05), New York Heart Association class (p < 0.05) and quality of life (p < 0.05), but no significant differences were observed between groups (p > 0.05). No significant changes were observed in brain natriuretic peptide in either group post-CRT. CONCLUSION: Based on pre-CRT implantation ventilatory gas exchange, subjects with the most impaired values appeared to have more improvement post-CRT, possibly associated with a decrease in RVSP.

Vasovagal syncope: an update on the latest pharmacological therapies.

INTRODUCTION: Syncope is an abrupt loss of consciousness in response to reduced perfusion to the brain. Neurocardiogenic or vasovagal syncope results from a complex neurologic reflex, and treatments to prevent recurrence attempt to modulate aspects of that reflex. AREAS COVERED: Pharmacologic treatments for vasovagal syncope address the syncope reflex in multiple ways. Fludrocortisone and sodium chloride increase systemic fluid volume. Midodrine, ß blockers and norepinephrine transport inhibitors modulate the sympathetic nervous system. Other treatments for syncope modulate other neurotransmitters or affect heart rate. The most recent trials evaluating established and novel therapies are reviewed. EXPERT OPINION: To reduce recurrence of vasovagal syncope, conservative measures are first line. If these fail to prevent recurrence, the most promising medical therapy includes midodrine. Randomized placebo-controlled data evaluating fludrocortisone, midodrine and ß blockers in older patients are awaited. Because of the significance of the placebo effect in this condition, any treatment must be evaluated in a randomized double-blind placebo-controlled trial before being accepted as effective.