Incidence and Predictors for Recurrence of Ventricular Arrhythmia Presenting During Acute Myocarditis: A Multicenter Study.

BACKGROUND: Management of acute myocarditis (AM) patients experiencing ventricular arrhythmia (VA) during acute illness is controversial, especially regarding early implantable cardioverter-defibrillator (ICD) implantation. OBJECTIVES: The purpose of this study was to evaluate the prevalence of and find predictors for long-term sustained VA recurrence and overall mortality among AM patients with VA. METHODS: This was a multicenter retrospective analysis of AM patients (verified by cardiac magnetic resonance imaging or myocardial biopsy) with documented VA during the acute illness ("initial VA"). Patients with history of myocardial infarction, heart failure, or VA were excluded. The study endpoint was a composite of sustained VA and overall mortality during follow-up. RESULTS: The study included 69 AM patients with initial VA: sustained monomorphic ventricular tachycardia (MMVT) (n = 25), sustained polymorphic ventricular tachycardia (VT)/ventricular fibrillation (n = 13), and nonsustained VT (n = 31). Age was 44 ± 13 years, and 23 of 69 (33.3%) were women. During median follow-up of 5.5 years, 27 of 69 (39%) patients reached the composite endpoint including sustained VA (n = 24) and death (n = 11). Initial MMVT, predischarge left ventricular dysfunction (left ventricular ejection fraction <50%), and anteroseptal delayed enhancement on cardiac magnetic resonance imaging were significantly associated with the composite endpoint. On multivariable analysis, initial MMVT (HR: 5.17; 95% CI: 1.81-14.6; P = 0.001) and predischarge LV dysfunction (HR: 4.57; 95% CI: 1.83-11.5; P = 0.005) were independently associated with the composite endpoint. Using these 2 predictors, we could delineate subgroups with low (∼4%), medium (∼42%), and high (∼82%) 10-year incidence of composite endpoint. CONCLUSIONS: AM patients presenting with VA have high incidence of sustained VA recurrence and mortality posthospitalization. Initial MMVT and predischarge LV dysfunction are independently associated with VA recurrence and mortality. Implantable cardioverter-defibrillator implantation may be considered in such high-risk patients.

Amiodarone and pulmonary toxicity in atrial fibrillation: a nationwide Israeli study.

BACKGROUND AND AIMS: Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used. METHODS: A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC. RESULTS: The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses. CONCLUSION: In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality.

Compound Heterozygosity for Late-Onset Cardiomyopathy-Causative ALPK3 Coding Variant and Novel Intronic Variant Cause Infantile Hypertrophic Cardiomyopathy.

Hypertrophic and dilated cardiomyopathy (HCM, DCM) are leading causes of cardiovascular morbidity and mortality in children. The pseudokinase alpha-protein kinase 3 (ALPK3) plays an essential role in sarcomere organization and cardiomyocyte differentiation. ALPK3 coding mutations are causative of recessively inherited pediatric-onset DCM and HCM with variable expression of facial dysmorphism and skeletal abnormalities and implicated in dominantly inherited adult-onset cardiomyopathy. We now report two variants in ALPK3-a coding variant and a novel intronic variant affecting splicing. We demonstrate that compound heterozygosity for both variants is highly suggestive to be causative of infantile-onset HCM with webbed neck, and heterozygosity for the coding variant presents with adult-onset HCM. Our data validate partial penetrance of heterozygous loss-of-function ALPK3 mutations in late-onset hypertrophic cardiomyopathy and expand the genotypic spectrum of autosomal recessive ALPK3-related cardiac disease with Noonan-like features.

Clinical Outcomes of Patients with COVID-19 Infection and Cardiac Implantable Electronic Devices.

BACKGROUND: Existing cardiac disease contributes to poor outcome in patients with coronavirus disease 2019 (COVID-19). Little information exists regarding COVID-19 infection in patients with a cardiac implantable electronic device (CIED). OBJECTIVES: To assess the association between CIEDs and severity of COVID-19 infection. METHODS: We performed a retrospective analysis including 13,000 patients > 18 years old with COVID-19 infection between January and December 2020. Patients with COVID-19 who had a permanent pacemaker or defibrillator were matched 1:4 based on age and sex followed by univariate and multivariate analyses. Baseline characteristics and clinical outcomes were assessed. RESULTS: Forty patients with CIED and 160 patients without CIED were included in the current analysis. Mean age was 72.6 ± 13 years, and approximately 50% were females. Majority of the patients in the study arm had a pacemaker (63%), whereas only 15 patients (37%) had a defibrillator. Patients with COVID-19 and CIED presented more often with atrial fibrillation, coronary artery disease, heart failure, hypertension, diabetes, and chronic kidney disease. They were more likely to be hospitalized in the intensive care unit (ICU) and required more ventilatory support (35% vs. 18.3%). Thirty-day mortality (22.5% vs. 13.8%) and 1-year mortality (25% vs. 15%) were higher among patients with COVID-19 and CIED. CONCLUSIONS: Patients with COVID-19 and CIED had a significantly higher prevalence of co-morbidities that were associated with increased mortality. Although, CIED by itself was not found as an independent risk factor for morbidity and mortality, it may serve as a warning for severe illness with COVID-19.

A case report of a young patient with both Brugada and long QT3 syndrome: between the hammer and the anvil.

BACKGROUND: Brugada syndrome (BrS) is an inherited disorder associated with increased risk of ventricular arrhythmias and sudden cardiac death. The most common genetic alteration is a loss of function mutation of SCN5A gene. Several mutations in SCN5A gene were found to be associated with an overlap phenotype of both BrS and long QT3 (LQT3) syndrome. CASE SUMMARY: We report of a 29-year-old man with familial LQT3 syndrome that was diagnosed at age 6 during evaluation of syncope. He has been treated for several years with Flecainide. Now presented with recurrent episodes of syncope. Electrocardiogram (ECG) upon admission was notable for Brugada type 1 pattern that was attenuated after Flecainide was discontinued. Genetic analysis revealed SCN5A 1790D>G mutation that is associated with overlap of LQT3 and BrS. Due to recurrent syncope and difficult management of both LQT3 and BrS, an implantable cardioverter-defibrillator was implanted together with beta-blockers treatment. The patient was discharged home with no evidence of Brugada type 1 pattern on his ECG. He had no further syncope or arrhythmias during 6 months of follow-up. DISCUSSION: There are few reports describing the phenotypic overlap between LQT3 and BrS. Despite the confirmed genetic link between both syndromes, their management strategy is controversial. In particularly, the treatment with sodium channel blockers for LQT3 syndrome may increase the risk for arrhythmias in patients with coexisting BrS. The present case demonstrates the link between LQT3 and BrS and the difficult dilemma in the management of these patients.

When the brain slows the heart-herpes encephalitis and sinus arrest: a case report.

BACKGROUND: Herpes simplex virus (HSV) encephalitis is a known cause of cognitive deterioration, neurological disturbances, and seizures though are rarely associated with sinus node dysfunction. CASE SUMMARY: We present a 54-year-old man admitted to the hospital with a 10-day history of fever, confusion, and fatigue, 1 week following a transient loss of consciousness. An initial workup suggested HSV encephalitis and the patient was started on intravenous Acyclovir. Due to his episode of syncope, a 24 h Holter electrocardiogram monitoring was performed. The Holter documented multiple episodes of sinus arrest, with a second episode of syncope noticed by the hospital staff concurrent with the last documented sinus arrest. Following antiviral treatment and resolution of the encephalitis we noticed complete resolution of sinus node dysfunction. We subsequently avoided permanent pacemaker implantation. DISCUSSION: Our case of proven HSV encephalitis complicated by sinus node arrest and syncope with complete resolution following antiviral treatment suggests no indication for permanent pacemaker implantation. This approach is consistent with data from previously reported cases.

Incidence and Clinical Outcomes of Pacing Induced Cardiomyopathy in Patients With Normal Left Ventricular Systolic Function and Atrioventricular Block.

Patients with preserved left ventricular (LV) ejection function (EF) and atrioventricular block (AVB) who are anticipated for high-burden of right ventricular (RV) pacing possess a risk to develop pacing-induced cardiomyopathy (PIC) and adverse clinical outcomes. Hence, the aim of the study is to evaluate the incidence, predictors, and clinical outcomes of RV PIC in patients with preserved LVEF, AVB, and high-burden of RV pacing. One thousand and thirteen patients with second or third-degree AVB underwent first time pacemaker implantation between January 2002 and August 2016. A total of 203 patients with a newly implanted pacemaker, normal baseline LVEF, and high burden of RV pacing were included in the present study. Follow-up echocardiography was examined for a new decrease in LVEF of 10% or higher. Alternative causes for cardiomyopathy were ruled out. Patient characteristics, echocardiographic measurements, device clinic data, mortality, and hospitalizations for heart failure were collected and compared between the PIC and the non-PIC groups. Fifty-one patients (25%) developed LV dysfunction with 22 patients (11%), showing LVEF < 40%. During a mean follow-up of 49.2 months, the risk of heart failure hospitalization or all-cause mortality was significantly higher in the PIC group versus non-PIC group (35.3% vs 19.1%, p = 0.009). In conclusion the incidence of PIC in patients with normal LVEF and AVB, who are anticipated for high-burden of RV pacing is high. PIC in patients with a previously normal LV function is associated with unfavorable long-term clinical outcomes, including higher rates of heart failure hospitalizations and all-cause mortality.

Commotio Cordis: Indeed?

We discuss an unusual case of a patient who initially presented with apparent commotio cordis but returned several months later with spontaneous wide complex tachycardia. This case highlights the importance of investigation of survivors of commotio cordis, especially if atypical, to determine if there is underlying cardiac disease. (Level of Difficulty: Beginner.).

Developing a risk score to predict mortality in the first year after implantable cardioverter defibrillator implantation: Data from the Israeli ICD Registry.

INTRODUCTION: Life expectancy of less than 1 year is usually a contraindication for implantable cardioverter defibrillator (ICD) implantation. The aim was to identify patients at risk of death during the first year after implantation. METHODS AND RESULTS: Data were derived from a prospective Israeli ICD Registry. Two groups of patients were compared, those who died and those who were alive 1 year after ICD implantation. Factors associated with 1-year mortality were identified on a derivation cohort. A risk score was established and validated. A total of 2617 patients have completed 1 year of follow-up after ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Age greater than 75 years (hazard ratio [HR], 2.7; 95% confidence interval [95% CI], 1.6 to 4.4), atrial fibrillation (AF; HR, 1.9; 95% CI, 1.12 to 3.17), chronic lung disease (HR, 2.0; 95% CI, 1.1 to 3.76), anemia (HR, 2.3; 95% CI, 1.3 to 3.93) and chronic renal failure (CRF; HR, 3.4; 95% CI, 1.74 to 6.6) were independent risk factors for 1-year mortality. We propose a simple AAACC ("triple A double C") score for prediction of 1-year mortality after ICD implantation: Age greater than 75 years (3 points(pts)), anemia (2 pts), AF (1 pt), CRF (3 pts) and chronic lung disease (1 pt). Mortality risk increased with rising number of points (from 1% with 0 pts to 12.5% with >4 pts). The risk score was evaluated with receiver operating characteristic curve and the area under the curve of the validation curve is 0.71 (95% CI, 0.66 to 0.76). CONCLUSIONS: Age greater than 75, AF, chronic lung disease, anemia, and CRF were independent risk factors for 1-year mortality. AAACC risk score identifies patients at high risk of death during 1 year after ICD implantation.

Arrhythmic Events in Brugada Syndrome: A Nationwide Israeli Survey of the Clinical Characteristics, Treatment; and Long-Term Follow-up (ISRABRU-VF).

BACKGROUND: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE). OBJECTIVES: To conduct the first nationwide survey focused on BrS patients with documented AE. METHODS: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2). RESULTS: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13-84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30-53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine. CONCLUSIONS: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.

Prominent differences in left ventricular performance and myocardial properties between right ventricular and left ventricular-based pacing modes in rats.

Biventricular pacing is an important modality to improve left ventricular (LV) synchronization and long-term function. However, the biological effects of this treatment are far from being elucidated and existing animal models are limited and demanding. Recently, we introduced an implanted device for double-site epicardial pacing in rats and echocardiographically demonstrated favorable effects of LV and biventricular (LV-based) pacing modes typically observed in humans. Here, this new animal model was further characterized. Electrodes were implanted either on the right atria (RA) and right ventricle (RV) or on the RV and LV. Following recovery, rats were either used for invasive hemodynamic measurements (pressure-volume analysis) or exposed to sustained RV vs. biventricular tachypacing for 3 days. RV pacing compromised, while LV-based pacing modes markedly enhanced cardiac performance. Changes in LV performance were associated with prominent compensatory changes in arterial resistance. Sustained RV tachypacing increased the electrocardiogram QTc interval by 7.9 ± 3.1 ms (n = 6, p < 0.05), dispersed refractoriness between the right and left pacing sites and induced important molecular changes mainly in the early-activated septal tissue. These effects were not observed during biventricular tachypacing (n = 6). Our results demonstrate that the rat is an attractive new model to study the biological consequences of LV dyssynchrony and resynchronization.

Successful treatment of ventricular fibrillation storm triggered by short-long-short sequence; time to avoid managed ventricular pacing.

Sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is caused by ventricular tachyarrhythmia that can be effectively treated by implantable cardioverter defibrillator (ICD) therapy. We report of a 28-year-old man with HCM and a dual chamber ICD, originally implanted for primary prevention of SCD, (programmed to AAI(R)-DDD(R); managed ventricular pacing (MVP) mode, Medtronic Inc. St Paul, MN USA). He presented with recurrent ICD shocks due to ventricular fibrillation (VF) despite antiarrhythmic therapy. Careful assessment of the stored electrograms demonstrated a repetitive pattern of VF initiation following short-long-short sequences. Initially, activation of ventricular rate stabilization (VRS) algorithm failed to prevent recurrent VF. Ultimately, deactivation of MVP and reprogramming the device to DDD mode with VRS on, resulted in arrhythmia suppression and avoidance of ICD shocks. Physicians should be aware that although VRS function is available in MVP mode, it does not function in the AAI mode during MVP; in order to effectively treat short-long-short sequence induced ventricular arrhythmia by device programming.

Swallow-induced syncope and carotid sinus hypersensitivity: Coincident or associated conditions?

Swallow induced syncope is a rare clinical condition which is thought to result from an abnormal vagal reflex leading to bradycardia and cerebral hypoperfusion. It mostly occurs in patients with organic or functional disorders of the esophagus, and often requires permanent pacemaker implantation, along with treatment of the underlying esophageal pathology. In the following case, we report of a 71-year-old male with achalasia post per oral endoscopic myectomy, who presented with syncope and documented AV-block while eating solid food. In addition, long sinus pauses were noted during carotid sinus massage, suggesting that the two distinct entities may be associated, and further supporting the mechanism of neurally mediated syncope in the pathophysiology of swallow-induced syncope.

Two to one CRTD pacing: When the T wave and the P wave interact.

We presented a unique phenomenon of 2:1 cardiac resynchronization therapy pacing due to T wave oversensing. Ultimately, by utilizing a unique feature of integrated bipolar sensing, we succeeded to eliminate the T wave oversensing signals, and restore 1:1 CRTD pacing. Importantly, this feature enabled us to overcome the T wave oversensing issue, without the need to decrease the ventricular sensitivity, which could potentially interfere with ventricular arrhythmia detection and appropriate shock delivery when required.

Contemporary rates and outcomes of single- vs. dual-coil implantable cardioverter defibrillator lead implantation: data from the Israeli ICD Registry.

AIMS: Dual-coil leads were traditionally considered standard of care due to lower defibrillation thresholds (DFT). Higher complication rates during extraction with parallel progression in implantable cardioverter defibrillator (ICD) technology raised questions on dual coil necessity. Prior substudies found no significant outcome difference between dual and single coils, although using higher rates of DFT testing then currently practiced. We evaluated the temporal trends in implantation rates of single- vs. dual-coil leads and determined the associated adverse clinical outcomes, using a contemporary nation-wide ICD registry. METHODS AND RESULTS: Between July 2010 and March 2015, 6343 consecutive ICD (n = 3998) or CRT-D (n = 2345) implantation patients were prospectively enrolled in the Israeli ICD Registry. A follow-up of at least 1 year of 2285 patients was available for outcome analysis. The primary endpoint was all-cause mortality. Single-coil leads were implanted in 32% of our cohort, 36% among ICD recipients, and 26% among CRT-D recipients. Secondary prevention indication was associated with an increased rate of dual-coil implantation. A significant decline in dual-coil leads with reciprocal incline of single coils was observed, despite low rates of DFT testing (11.6%) during implantation, which also declined from 31 to 2%. In the multivariate Cox model analysis, dual- vs. single-coil lead implantation was not associated with an increased risk of mortality [hazard ratio (HR) = 1.23; P= 0.33], heart failure hospitalization (HR = 1.34; P=0.13), appropriate (HR = 1.25; P= 0.33), or inappropriate ICD therapy (HR = 2.07; P= 0.12). CONCLUSION: Real-life rates of single-coil lead implantation are rising while adding no additional risk. These results of single-coil safety are reassuring and obtained, despite low and contemporary rates of DFT testing.

Impact of Point-of-Care Ultrasound Examination on Triage of Patients With Suspected Cardiac Disease.

Complementing the physical examination with a point-of-care ultrasound study (POCUS) can improve patient triage. We aimed to study the impact of POCUS on the diagnosis and management of outpatients and hospitalized patients with suspected cardiac disease. In this multicenter study, a pocket-sized device was used to perform POCUS when the diagnosis or patient management was unclear based on anamnesis, physical examination, and basic diagnostic testing. Eighteen physicians (cardiac fellows 49%, cardiologists 30%, and echocardiographers 21%) performed physical examinations extended by POCUS on 207 patients (inpatients 83% and outpatients 17%). POCUS findings resulted in a change in the primary diagnosis in 14% of patients. In patients whose diagnosis remained unchanged, POCUS results reinforced the initial diagnosis in 48% of the cases. In 39% of the patients, the diagnostic plan was altered, including referral (16%) or deferral (23%) to other diagnostic techniques. Alteration in medical treatment (drug discontinuation or initiation) occurred in 11% of the patients, and in 7% POCUS results influenced the decision whether to perform a therapeutic procedure. Hospitalization or discharge was determined after POCUS in 11% of the patients. In conclusion, during patient triage, extension of the physical examination by POCUS can cause physicians to alter their initial diagnosis, resulting in an immediate change of diagnostic and therapeutic procedures. Based on POCUS results, physicians altered the diagnostic plan either by avoiding or referring patients to other diagnostic procedures in almost half of the studied population.