Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

COVID-19 and Cardiac Arrhythmias: a Contemporary Review.

Purpose of Review: A significant proportion of patients infected by the severe acute respiratory syndrome-coronavirus (SARS-CoV2) (COVID-19) also have disorders affecting the cardiac rhythm. In this review, we provide an in-depth review of the pathophysiological mechanisms underlying the associated arrhythmic complications of COVID-19 infection and provide pragmatic, evidence-based recommendations for the clinical management of these conditions. Recent Findings: Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Summary: Arrhythmic complications from acute COVID-19 infection are commonly encountered in clinical practice, and COVID-19 patients with cardiac complications tend to have worse clinical outcomes than those without. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. Some manifestations, such as the long COVID syndrome, may lead to residual symptoms several months after acute infection. As the pandemic evolves with the discovery of new SARS-CoV2 variants, development and use of newer anti-viral and immuno-modulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.

Virtual Transformation and the Use of Social Media: Cardiac Electrophysiology Education in the Post-COVID-19 Era.

PURPOSE OF REVIEW: The COVID-19 pandemic has significantly impacted the delivery of education for all specialties, including cardiac electrophysiology. This review will provide an overview of the COVID-19 spurred digital transformation of electrophysiology education for practicing clinicians and trainees in electrophysiology and cover the use of social media in these educational efforts. RECENT FINDINGS: Major international, national, and local meetings and electrophysiology fellowship-specific educational sessions have transitioned rapidly to virtual and distanced learning, enhanced by social media. This has allowed for participation in educational activities by electrophysiologists on a wider, more global scale. Social media has also allowed rapid dissemination of new advances, techniques, and research findings in real time and to a global audience, but caution must be exercised as pitfalls also exist. SUMMARY: The digital and social media transformation of cardiac electrophysiology education has arrived and revolutionized the way education is delivered and consumed. Continued hybrid in-person and virtual modalities will provide electrophysiologists the flexibility to choose the best option to suit their individual needs and preferences for continuing education.

COVID-19 and cardiac arrhythmias: a global perspective on arrhythmia characteristics and management strategies.

BACKGROUND: Cardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients. However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described. We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey. METHODS: The Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe. The survey was active from March 27 to April 13, 2020. RESULTS: A total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents. Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital. Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias. Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively. There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication. One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA. Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM. Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management. CONCLUSIONS: In this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening. Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes. Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.

Combined Right Ventricular Outflow Tract Epicardial and Endocardial Late Potential Ablation for Treatment of Brugada Storm: A Case Report and Review of the Literature.

A 34-year-old man with Brugada syndrome (BrS) presented with electrical storm, manifested as multiple appropriate shocks from his implantable cardioverter-defibrillator over a period of 7 hours. He had not tolerated prior treatment with quinidine, and had self-discontinued cilostazol citing persistent palpitations. After stabilization with intravenous isoproterenol, an electrophysiology study was performed but no spontaneous or induced ventricular ectopic beats were identified. A three-dimensional (3D) endocardial electro-anatomic map of the right ventricular outflow tract (RVOT), pulmonic valve, and pulmonary artery, as well as a 3D epicardial map of the RVOT, were created. Low voltage, complex, fractionated electrograms and late potentials were targeted for irrigated radiofrequency ablation both endocardially and epicardially. Post-procedure, he was maintained on cilostazol (referring clinician preference), and has had no further ventricular tachyarrhythmia episodes over the past forty-one months. We propose that this novel ablation strategy may be useful for acute management of selected patients with BrS.

The Use of Contrast-enhanced Ultrasonography for Imaging of Carotid Atherosclerotic Plaques: Current Evidence, Future Directions.

Contrast-enhanced ultrasonography (CEUS) is a rapidly evolving modality for imaging carotid artery disease and systemic atherosclerosis. CEUS coupled with diagnostic ultrasonography predicts the degree of carotid artery stenosis and is comparable with computed tomography and magnetic resonance angiography. This article reviews the literature on the evolving role of CEUS for the identification and characterization of carotid plaques with an emphasis on detection of intra-plaque neovascularization and related high-risk morphologic features notably present in symptomatic patients. CEUS carotid imaging may play a prominent additive role in risk stratifying patients and serve as a powerful tool for monitoring therapeutic interventions.

Usefulness of an Echocardiographic Composite Cardiac Calcium Score to Predict Death in Patients With Stable Coronary Artery Disease (from the Heart and Soul Study).

Mitral annular calcium and aortic valve sclerosis on transthoracic echocardiography (TTE) are independently associated with cardiovascular (CV) events in patients with coronary artery disease (CAD). However, the prognostic value of calcific deposits at multiple sites is unknown. We performed TTEs in a prospective cohort of 595 outpatients with stable CAD and graded the severity of calcific deposition at 6 sites: mitral annulus, aortic valve, aortic ring, sinotubular junction, papillary muscle tip, and left main coronary artery. For each site with moderate calcific deposition or greater, 1 point was given to generate a composite cardiac calcium score (maximum of 6). The primary end point was the occurrence of CV events-a composite of death, myocardial infarction, stroke, transient ischemic attack, and heart failure. The association of the composite calcium score with CV events was evaluated using multivariate Cox proportional hazards models. Over a median follow-up of 4.2 years, 205 CV events occurred. Participants with a composite calcium score ≥2 had a higher risk of CV events (11.1 events/100 person-years) than those with a score of 0 (5.5 events/100 person-years, unadjusted hazard ratio [HR] 2.01, p <0.001), but this association was not significant after multivariate adjustment. The risk of death was higher in participants with a composite calcium score of ≥2 (8.9 events/100 person-years) versus those with a score of 0 (3.6 events/100 person-years, unadjusted HR 2.51, p <0.001). After adjustment for age, diabetes mellitus, previous coronary revascularization, diastolic blood pressure, estimated glomerular filtration rate, and serum phosphorus level, the risk of death remained higher in participants with a composite calcium score of ≥2 compared with those with a score of 0 (adjusted HR 1.76, 95% confidence interval 1.10 to 2.81, p = 0.02). In conclusion, a simple TTE-derived composite cardiac calcium score was independently predictive of death in patients with pre-existing CAD.

Glomerular cell death and inflammation with high-protein diet and diabetes.

BACKGROUND: Overfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of high-protein diets and/or diabetes in vitro with proof-of-concept appraisal in vivo. METHODS: Mouse podocytes and mesangial cells were cultured under control and metabolic stressor conditions: (i) no addition; (ii) increased AAs (4-6-fold>control); (iii) high glucose (HG, 30.5 mM); (iv) AA/HG combination; (v) AGE-bovine serum albumin (AGE-BSA, 300 µg/mL); (vi) BSA (300 µg/mL). RAGE was inhibited by blocking antibody. Diabetic (streptozotocin) and nondiabetic mice (C57BL/6J) consumed diets with protein calories of 20 or 40% (high) for 20 weeks. People with DKD and controls provided 24-h urine samples. RESULTS: In podocytes and mesangial cells, apoptosis (caspase 3/7 activity and TUNEL) increased in all metabolic stressor conditions. Both inflammatory mediator expression (real-time reverse transcriptase-polymerase chain reaction: serum amyloid A, caspase-4, inducible nitric oxide synthase, and monocyte chemotactic protein-1) and RAGE (immunostaining) also increased. RAGE inhibition prevented apoptosis and inflammation in podocytes. Among mice fed high protein, podocyte number (WT-1 immunostaining) decreased in the diabetic group, and only these diabetic mice developed albuminuria. Protein intake (urea nitrogen) correlated with AGE excretion (carboxymethyllysine) in people with DKD and controls. CONCLUSIONS: High-protein diet and/or diabetes-like conditions increased glomerular cell death and inflammation, responses mediated by RAGEs in podocytes. The concept that high-protein diets exacerbate early indicators of DKD is supported by data from mice and people.

Hyperlipidaemia and cardiovascular disease: do fibrates have a role?

PURPOSE OF REVIEW: Fibrates continue to be a viable treatment option for mixed atherogenic dyslipidemia, and recent reports from clinical studies have shed new light on the therapeutic utility of fibrates for the prevention of microvascular and macrovascular disease, especially in combination with statins. RECENT FINDINGS: Data from randomized placebo-controlled trials have shown that fibrates reduce nonfatal coronary events but do not confer any benefit on mortality or other adverse cardiovascular outcomes. The ACCORD Lipid trial studied the additive effect of fenofibrate therapy along with low-dose simvastatin therapy in 5,518 patients with type 2 diabetes mellitus, and found that fenofibrate did not affect any of the adverse cardiovascular outcomes, either individually or as part of a composite outcome, after 4.7 years of follow-up. An a priori subgroup analysis showed a significant benefit from fenofibrate-simvastatin combination therapy over simvastatin alone in participants with moderate hypertriglyceridemia and low HDL-cholesterol on major cardiovascular events, consistent with post-hoc analyses of previous fibrate trials. The ACCORD-Eye study adds to the sparse clinical data on the effect of fenofibrate on diabetic retinopathy, and showed that fenofibrate may be used to reduce the risk of progression of diabetic retinopathy even in patients with established disease. The combination of statin and fibrate was well tolerated. SUMMARY: Fibrate therapy does not reduce mortality but may reduce nonfatal coronary events in patients at risk for cardiovascular disease, including those with type 2 diabetes. The ACCORD Lipid study shows that the combination of low-dose simvastatin and fenofibrate is well tolerated, and is potentially cardioprotective in patients with atherogenic 'mixed' dyslipidemia.

Influence of glycemic control on the development of diabetic cardiovascular and kidney disease.

Diabetes mellitus leads to the development of a host of micro- and macrovascular complications, which collectively lead to substantial morbidity and mortality. Among the microvascular complications of diabetes, diabetic kidney disease is the most common. Macrovascular complications from diabetes lead to a 2- to 4-fold increase in the incidence of cardiovascular disease and up to twice the mortality from cardiovascular causes as compared with nondiabetic individuals. This article discusses the various drug classes used to treat diabetes mellitus, and reviews the current clinical evidence linking glycemic control using these drug classes on diabetic kidney and cardiovascular disease.

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus--a pooled meta-analysis of randomized placebo-controlled clinical trials.

OBJECTIVE: Fibrates are thought to be useful anti-dyslipidemic agents particularly in patients with diabetes mellitus and dyslipidemia characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. We conducted a systematic review and meta-analysis of long-term randomized controlled trials to evaluate the role of fibrates in the prevention of cardiovascular events in patients with type 2 diabetes mellitus. DATA SOURCES: English-language journals indexed in Index Medicus/MEDLINE and the Cochrane Collaboration databases (through December 2007), unpublished data from selected clinical trials. DATA EXTRACTION AND ANALYSIS: A total of 11,590 patients from 6 published randomized placebo-controlled trials were analyzed using pooled meta-analysis techniques. Relative risks were computed for various cardiovascular outcomes and mortality, and statistical significance was tested using the z-test statistic (two-sided alpha error <0.05). RESULTS: The use of fibrates did not significantly affect the risk of all-cause mortality or cardiac mortality, and also did not affect the risk of stroke, unstable angina, or invasive coronary revascularization. However, the relative risk of non-fatal myocardial infarction was significantly reduced by about 21% (pooled relative risk 0.79, p=0.006) with the use of fibrates. CONCLUSIONS: Long-term use of fibrates in patients with type 2 diabetes mellitus significantly reduces the risk of non-fatal myocardial infarction, but has no significant effect on mortality or on other adverse cardiovascular outcomes.

Modulation of advanced glycation end products by candesartan in patients with diabetic kidney disease--a dose-response relationship study.

Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria ≥500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure. At baseline and after each dosing period, blood pressure measurements and 24-hour urine collections were obtained. Urinary carboxymethyl lysine, an AGE biomarker, was reduced over the 12-week dose escalation protocol (r = 0.38, P = 0.01) in DKD participants. Creatinine clearance increased slightly, but albuminuria was unaffected by candesartan administration. Baseline urinary transforming growth factor-ß1 excretion was lower in DKD participants than in controls and did not change during the study period. Reducing kidney exposure to AGEs may be a mechanism of protection by angiotensin receptor blockade in DKD. AGEs may also impact the diabetic kidney through mechanisms independent of transforming growth factor-ß1.

Should albuminuria be a focus of antihypertensive therapy goals?

Albuminuria has been recognized as a risk marker for both chronic kidney disease and cardiovascular disease in large observational cohorts. In addition, post hoc analyses of many large randomized trials have found a positive relationship between albu-minuria and adverse renal and cardiovascular outcomes, leading some to suggest that albuminuria may be a potential therapeutic target for antihypertensive treatment. However, direct clinical evidence linking albuminuria reduction to reduction in adverse renal and cardiovascular events is scarce. This paper reviews the evidence in the current literature to address whether albuminuria can be used as a credible predictor of risk for chronic kidney disease and cardiovascular disease and also reviews the clinical trial evidence to appraise the prospect of using albuminuria as a therapeutic target to prevent adverse renal and cardiovascular events.

Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function.

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.