High Risk Of Sudden Death Research Articles

Новый электрокардиографический феномен при синдроме удлиненного интервала QT: клиническое наблюдение

Long QT syndrome (LQTS) is a disease with a high risk of sudden death in children. Individual prognosis is based on additional, primarily electrocardiological markers. Authors represent a clinical case of a rare variant of electrocardiographic manifestation of LQTS in children that wasn’t described previously. A 6 y/o female patient with LQTS, had no complaints, no syncope or sudden death familial cases. The molecular genetic study revealed a de novo mutation in the SCN5A gene which is typical for the third molecular genetic variant of LQTS (LQT3). Holter monitoring noted “hyperadaptation” of the QT interval (slope QT/RR 0.37 with a norm of up to 0.24). During night sleep, episodes of combined T-wave and QRS complex alternans (AT/AQRS) were detected. This pattern has not been previously described in patients with LQTS. Possible mechanisms and prognostic value for the revealed ECG pattern, issues of treatment of patients with LQT3 are discussed. Conclusion: combined T-wave and QRS complex alternans (AT/AQRS) is a new, previously undescribed ECG phenomenon in patients with LQTS that is highly likely to increase the risk for cardiac events. Thus the “hyperadaptation” of the QT interval may be one of the electrocardiological signs of LQT3.

Neurocardiac pathologies associated with potassium channelopathies.

Voltage-gated potassium channels are expressed throughout the human body and are essential for physiological functions. These include delayed rectifiers, A-type channels, outward rectifiers, and inward rectifiers. They impact electrical function in the heart (repolarization) and brain (repolarization and stabilization of the resting membrane potential). KCNQx and KCNHx encode Kv7.x and Kv11.x proteins, which form delayed rectifier potassium channels. KCNQx and KCNHx channelopathies are associated with both cardiac and neuronal pathologies. These include electrocardiographic abnormalities, cardiac arrhythmias, sudden cardiac death (SCD), epileptiform discharges, seizures, bipolar disorder, and sudden unexpected death in epilepsy (SUDEP). Due to the ubiquitous expression of KCNQx and KCNHx channels, abnormalities in their function can be particularly harmful, increasing the risk of sudden death. For example, KCNH2 variants have a dual role in both cardiac and neuronal pathologies, whereas KCNQ2 and KCNQ3 variants are associated with severe and refractory epilepsy. Recurrent and uncontrolled seizures lead to secondary abnormalities, which include autonomics, cardiac electrical function, respiratory drive, and neuronal electrical activity. Even with a wide array of anti-seizure therapies available on the market, one-third of the more than 70 million people worldwide with epilepsy have uncontrolled seizures (i.e., intractable/drug-resistant epilepsy), which negatively impact neurodevelopment and quality of life. To capture the current state of the field, this review examines KCNQx and KCNHx expression patterns and electrical function in the brain and heart. In addition, it discusses several KCNQx and KCNHx variants that have been clinically and electrophysiologically characterized. Because these channel variants are associated with multi-system pathologies, such as epileptogenesis, Kv7 channel modulators provide a potential anti-seizure therapy, particularly for people with intractable epilepsy. Ultimately an increased understanding of the role of Kv channels throughout the body will fuel the development of innovative, safe, and effective therapies for people at a high risk of sudden death (SCD and SUDEP).

Arrhythmias and Hypertrophic Cardiomyopathy: Unravelling the Connection.

Hypertrophic cardiomyopathy (HCM) results from gene mutations affecting cardiac sarcomeres and is inherited in an autosomal dominant manner. With a prevalence of 1:200-1:500 in the general population, HCM is characterised by a hypertrophied and non-dilated left ventricle with predominant involvement of the interventricular septum. The myocardium's structural and intracellular factors, combined with triggers such as physical exertion, autonomic dysfunction, and ischemia, can lead to reentry events, and atrial and ventricular arrhythmias, including atrial fibrillation (AF) which is common among HCM patients. To manage the increased risk of mortality arising from congestive heart failure and thromboembolism, in patients with AF long-term anticoagulation and antiarrhythmic drugs are employed. HCM patients may also encounter supraventricular and ventricular arrhythmias, such as nonsustained ventricular tachycardia and ventricular premature beats, which can potentially lead to sudden cardiac death and necessitate treatment with implanted defibrillators. Physicians must comprehensively analyse clinical, anatomical, hemodynamic, rhythmic, functional, and genetic characteristics to identify HCM patients at high risk of sudden death. This article aims to discuss the pathophysiology of arrhythmia in HCM and clinical recommendations for various ventricular and atrial fibrillation including catheter ablation and implantable cardioverter-defibrillator (ICD).

Printable Poly(3,4-ethylenedioxythiophene)-Based Conductive Patches for Cardiac Tissue Remodeling.

Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery. In this work, we present a printable cardiac hydrogel that can exert functional effects on networks of cardiac myocytes. The hydrogel matrix was designed from poly(vinyl alcohol) (PVA) dynamically cross-linked with gallic acid (GA) and the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting patches exhibited excellent electrical conductivity, elasticity, and mechanical and contractile strengths, which are critical parameters for reinforcing weakened cardiac contraction and impulse propagation. Furthermore, the PVA-GA/PEDOT blend is suitable for direct ink writing via a melting extrusion. As a proof of concept, we have proven the efficiency of the patches in propagating the electrical signal in adult mouse cardiomyocytes through in vitro recordings of intracellular Ca2+ transients during cell stimulation. Finally, the patches were implanted in healthy mouse hearts to demonstrate their accommodation and biocompatibility. Magnetic resonance imaging revealed that the implants did not affect the essential functional parameters after 2 weeks, thus showing great potential for treating cardiomyopathies.

Sudden cardiac death in young athletes: exome sequencing results

BACKGROUND: Ranking risks and prevention of sudden cardiac death in professional young athletes is a crucial unresolved problem in sports medicine. Intense physical exertion can lead to adaptive changes in the cardiovascular system, which can mask inherited diseases with predominant myocardial involvement, such as hypertrophic cardiomyopathy. Undiagnosed cases of such diseases can be a risk factor for fatal outcomes associated with training and competitive activities, making this problem extremely relevant.
 AIM: To conduct a diagnostic search for possible molecular causes of cardiovascular diseases associated with a high risk of sudden death in young athletes.
 MATERIALS AND METHODS: Whole-exome sequencing of DNA extracted from two groups of biomaterials was performed: nine autopsy samples of heart tissues from young athletes who died during intense physical exertion and three venous blood samples from active athletes of the Russian national team. Obtained data were subjected to bioinformatic analysis and clinical interpretation.
 RESULTS: In total, 12 DNA samples were analyzed using a panel of 277 genes associated with the development of cardiovascular diseases with a high risk of sudden death. In 4 of 12 samples (33.3%), variants possibly related to the phenotype were found upon clinical interpretation of the sequencing results. A pathogenic variant was found in the MYBPC3 gene, leading to the development of hypertrophic cardiomyopathy (OMIM: 115197), and a potential pathogenic variant was found in the TRPM4 gene, associated with progressive familial heart block type IB (OMIM: 618531). Moreover, two variants with uncertain clinical significance were found in CAV3 and SCN1B.
 CONCLUSION: Currently, data from high-throughput sequencing are collected to identify the molecular basis of cardiovascular diseases with a high risk of sudden cardiac death. Identifying young athletes who are carriers of pathogenic and possibly pathogenic gene variants is beneficial for preventing fatal outcomes and personalizing medical support for professional athletes.

Fatal Coronary Artery Anomaly Concealed in Young Athletes with Exertional Syncope

Background. Syncope is a common symptom in children, many of which are benign and do not require treatment. Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital malformation but can be a risk for serious cardiovascular events, including sudden death as well as cardiogenic syncope. Case Report. We describe the case of a 14-year-old boy who suffered an initial syncope and afebrile seizure during a soccer game. A detailed medical history and imaging studies led to the diagnosis of the anomalous aortic origin of the left main coronary artery with an intramural course (AAOLCA-IM). Conclusion. Symptomatic AAOLCA-IM has the highest risk of sudden death among AAOCA, and surgical repair may be performed. Onset during exercise or preceding chest symptoms are suspicious signs of cardiogenic syncope and should be considered for cardiovascular imaging evaluation.

Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.

Continuous monitoring with implantable loop recorder detects arrhythmic risk in adults with systemic right ventricle following atrial switch

Abstract Background Patients with a systemic right ventricular circulation following atrial switch are at high risk of sudden death despite current monitoring strategies and advances in heart failure management. Arrhythmia represents a significant risk factor and early detection and intervention is of great value. The current surveillance approach with intermittent ambulatory monitoring is limited and cumbersome. Purpose We hypothesise that continuous rhythm monitoring with an implantable loop recorder (ILR) in the systemic right ventricle population will allow early detection of clinically significant arrhythmias. Methods Patients under follow up with a systemic right ventricular circulation following atrial switch were offered ILR implantation as an alternative to the standard of care (ambulatory 24-hour ECG). Patients with pre-existing intra-cardiac pacing devices or palliative were excluded. Following implantation, recordings made with symptoms or automatically following detection of significant arrhythmias. This included pauses over 3 seconds, atrioventricular block or supraventricular tachycardia. Transmission were reviewed daily and significant findings discussed in an adult congenital heart disease and electrophysiology MDT. Patients otherwise had routine clinical care. Results 24 patients had implantation of a loop recorder (67% of eligible cohort). They were aged 29-49 years (median 35 years) and 50% had additional lesions. Right ventricular function was normal in 42% and 29% had moderate or severe tricuspid regurgitation. 75% of the cohort were NYHA classification I. All but one patient were in sinus rhythm and 8 (33%) had previous intra-atrial re-entry tachycardia (IART). No patient had previously documented significant conduction disease. Implants were undertaken over 6 years without complications. 18 patients (75%) had automated or symptom activated recordings (52% automated) with a median of 2.8 recordings per patient (range 0 – 8 per patient) over 39.5 months (1.6 – 72.5 months). The recordings were clinically significant in 64% of the cohort (Table). This included 2 (9% of entire cohort) patients with atrioventricular block only, 11 patients (46%) with IART only and 4 patients (17%) with both IART and conduction disease (1 with atrioventricular block). These recordings resulted in 5 pacemaker implants (3 for atrioventricular block) and 2 further patients declined a device (1 subsequent death). 4 patients underwent, or are awaiting, ablation for IART. Risk scoring for sudden death did not predict arrhythmia events or atrioventricular block (1) (Figure). Conclusions Empirical ILR implantation in this low-risk systemic right ventricle cohort was well tolerated and detected a high burden of significant arrhythmias requiring intervention. Arrythmias were not predicted by risk scoring. This monitoring approach is an effective alternative to intermittent ambulatory surveillance however the impact on sudden death is unclear.

Right hepatectomy under cardiopulmonary bypass for hepatocellular carcinoma with inferior vena cava tumor thrombus: a case report

BackgroundThe prognosis of hepatocellular carcinoma (HCC) with vascular invasion is extremely poor, especially in patients with tumor thrombus (TT) of the inferior vena cava (IVC), which is an oncological emergency with a high risk of sudden death due to TT extension or migration. Herein, we describe a case of HCC with TT of the IVC that rapidly extended into the right atrium (RA), in which right hepatectomy was performed under cardiopulmonary bypass.Case presentationA 64-year-old man was diagnosed with HCC with IVC TT, and right hepatic lobectomy was scheduled. While awaiting surgery, he complained of respiratory distress and rushed to the emergency room. The TT had reached the RA, and the patient was in a state of oncologic emergency. We requested the cooperation of the cardiovascular surgery department, and under artificial cardiopulmonary support, the right atrium was incised, and a part of the TT was removed. The IVC was clamped to prevent tumor dispersal, and right hepatic lobectomy was performed. The remaining thrombus was excised along with the right lobe of the liver by incising the IVC. There were no serious postoperative complications, and the patient is alive 1 year and 5 months postoperatively.ConclusionHepatic resection with cardiopulmonary bypass could be an option for HCC with TT reaching the RA.

Penyuluhan Kesehatan Dampak Rokok Bagi Kesehatan Siswa Siswi SD Negeri 8 Benteng

Smoking behavior is a public health problem because it can cause various diseases and even death. Smokers have a 2-4 times greater risk of developing coronary heart disease and a higher risk of sudden death. Smoking also has a negative impact on passive smokers, passive smokers inhale more substances contained in cigarette smoke than active smokers, passive smokers inhale 2 times more nicotine, 5 times more carbon monoxide, 3 times more tar, and 50 times more more chemicals that are harmful to health. From this education, knowledge is also provided on how to prevent smoking. With health education provided to teenagers, teenagers will increase their knowledge about the dangers of smoking.

Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1.

Left ventricular noncompaction (LVNC) is a prevalent cardiomyopathy associated with excessive trabeculation and thin compact myocardium. Patients with LVNC are vulnerable to cardiac dysfunction and at high risk of sudden death. Although sporadic and inherited mutations in cardiac genes are implicated in LVNC, understanding of the mechanisms responsible for human LVNC is limited. We screened the complete exome sequence database of the Pediatrics Cardiac Genomics Consortium and identified a cohort with a de novo CHD4 (chromodomain helicase DNA-binding protein 4) proband, CHD4M202I, with congenital heart defects. We engineered a humanized mouse model of CHD4M202I (mouse CHD4M195I). Histological analysis, immunohistochemistry, flow cytometry, transmission electron microscopy, and echocardiography were used to analyze cardiac anatomy and function. Ex vivo culture, immunopurification coupled with mass spectrometry, transcriptional profiling, and chromatin immunoprecipitation were performed to deduce the mechanism of CHD4M195I-mediated ventricular wall defects. CHD4M195I/M195I mice developed biventricular hypertrabeculation and noncompaction and died at birth. Proliferation of cardiomyocytes was significantly increased in CHD4M195I hearts, and the excessive trabeculation was associated with accumulation of ECM (extracellular matrix) proteins and a reduction of ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif 1), an ECM protease. We rescued the hyperproliferation and hypertrabeculation defects in CHD4M195I hearts by administration of ADAMTS1. Mechanistically, the CHD4M195I protein showed augmented affinity to endocardial BRG1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4). This enhanced affinity resulted in the failure of derepression of Adamts1 transcription such that ADAMTS1-mediated trabeculation termination was impaired. Our study reveals how a single mutation in the chromatin remodeler CHD4, in mice or humans, modulates ventricular chamber maturation and that cardiac defects associated with the missense mutation CHD4M195I can be attenuated by the administration of ADAMTS1.

Description of a Cohort with a New Truncating MYBPC3 Variant for Hypertrophic Cardiomyopathy in Northern Spain

The pathogenicity of the different genetic variants causing hypertrophic cardiomyopathy (HCM) and the genotype/phenotype correlations are difficult to assess in clinical practice, as most mutations are unique or identified in non-informative families. Pathogenic variants in the sarcomeric gene MYBPC3 inherited with an autosomal dominant pattern, whereas incomplete and age-dependent penetrance are the most common causes of HCM. We describe the clinical characteristics of a new truncating MYBPC3 variant, p.Val931Glyfs*120, in 75 subjects from 18 different families from northern Spain with the p.Val931Glyfs*120 variant. Our cohort allows us to estimate the penetrance and prognosis of this variant. The penetrance of the disease increases with age, whereas 50% of males in our sample developed HCM by the age of 36 years old, and 50% of women developed the disease by the time they reached 48 years of age (p = 0.104). Men have more documented arrhythmias with potential risk of sudden death (p = 0.018), requiring implantation of cardioverter defibrillators (p = 0.024). Semi-professional/competitive sport among males is related to earlier onset of HCM (p = 0.004). The p.Val931Glyfs*120 truncating variant in MYBPC3 is associated with a moderate phenotype of HCM, with a high penetrance, onset in middle age, and a worse outcome in males due to higher risk of sudden death due to arrhythmias.

Lock the Doors: The Myocarditis Disaster and a call for the broad examination of the CDC and FDA

“Lock the doors.” uttered by LeRoy Cain, the flight director of STS-107, meant the complete loss of Space Shuttle Columbia. Locking the doors initiated the protocol to preserve data and logs for the impending investigation. Some hard lessons were learned from the Space Shuttle Challenger disaster 17 years earlier, one of which was that the National Aeronautics and Space Administration (NASA) should not be put in a position to investigate itself. The interagency Columbia Accident Investigation Board (CAIB) was formed to learn what we could from the fate of Columbia. Had NASA been the investigating agency, given the culture, it is possible the concluding cause would have been a random event such as bird strike after takeoff or micrometeoroid in orbit. “We are convinced that the management practices overseeing the Space Shuttle Program were as much a cause of the accident as the foam that struck the left wing.”[1] Those management practices point to lock-stepping, where dissenting opinions are discouraged or suppressed. NASA’s opinion was that foam is safe. When Bob Page, chair of NASA’s Intercenter Photo Working Group, saw foam strike the wing he raised an alarm that the heat shield may be compromised. He and two members of the Debris Assessment Team made a total of three requests to the Department of Defense (DoD) to obtain high-resolution images of Columbia’s left wing. A request that, by all accounts, the DoD was willing and able to fulfill. Those requests were subsequently canceled by the shuttle program managers. The CAIB report went on to say, “[t]he Board was also influenced by discussions with members of Congress, who suggested that this nation needed a broad examination of NASAʼs Human Space Flight Program, rather than just an investigation into what physical fault caused Columbia to break up during re-entry.” There are two vitally important lessons we have learned from NASA. The first is that a government agency should not be able to investigate itself. The second is that lock-stepping is lethal. The most advanced population health surveillance in the United States couldn’t find a single healthy child who died of COVID-19. Zero is a powerful number. Zero is also the number of vaccines that impart superior immunity over that of natural immunity. If we could choose one feature that the emergent 5th endemic cold virus could have, it would unequivocally be a minimal effect on children – safeguarding our future and allowing the progression of natural immunity. There is nothing mild about pediatric myocarditis. Even with the best medical management, 1/3rd of all patients never completely recovers, and will live with dilated cardiomyopathy. If untreated, 80% of children will develop chronic heart disease. These children are subject to a high risk of sudden death and may require an urgent heart transplant[2].

Rescue Balloon Aortic Valvuloplasty for Malignant Ventricular Arrhythmias and Cardiogenic Shock

Introduction: Severe Calcific Aortic Stenosis (AS) remains a major cause of morbidity and mortality in aged population. Asymptomatic with reduced LVEF has high risk of sudden death. Aim: To study the complexity of clinical course of Severe Calcific AS with LV Dysfunction. Case Report: A Seventy-Six-year-old male was admitted with ACS, NSTEMI, LVEF 35% and Severe Calcific AS. With plan of AVR, CAG was done and showed Mild CAD. Post-procedure he had sequence of catastrophic clinical events that includes, A systolic Cardiac Arrest (reverted after CPR) and Protracted Pulmonary edema (Connected to Mechanical Ventilation). Later had Malignant Ventricular Arrhythmias, treated with 34 times DC Shocks. He was not suitable for Surgical AVR or TAVI. After high-risk consent, he successfully underwent emergency Aortic Balloon Valvuloplasty (ABV) with significant drop in AV gradients. Post ABV, also had Paroxysmal AF. Arrhythmias were also treated with Beta blocker, Antiarrhythmics, Digoxin and Potassium supplementation. Gradually stabilized, discharged and followed up. Discussion: Aortic stenosis, a disease of elderly age group. Symptomatology varies widely. It has limited management options. In our case, Post CAG critical illness was probably due to “Pre -CAG” LV dysfunction with subclinical symptoms. ABV used as bail out the procedure in high-risk patients. Conclusion: ABV is considered as a viable palliative option, with the introduction of smaller profile balloons, rapid pacing and vascular closure devices. ABV can safely used as bridging procedure before Surgical AVR or TAVI in high-risk patients

Atrial Fibrillation in Wolff Parkinson White Syndrome: About a Case in Senegal

WOLFF PARKINSON and WHITE (WPW) syndrome is the most common form of pre-excitation. It is associated in some cases with atrial fibrillation with a high risk of sudden death. We report the case of a 64-year-old hypertensive woman with a history of ischemic stroke. She presented with hyperkinetic palpitations without hemodynamics instability on admission. The electrocardiogram recorded a complete tachyarrhythmia by pre-excitation atrial fibrillation, with a mean rate of 300 beats per minute. Electrophysiological investigation revealed an accessory pathway located at the ostium of the coronary sinus, which was successfully ablated by radiofrequency. A drug treatment based on flecaine 100 mg was introduced. The patient was asymptomatic after one month of outpatient follow-up.

Risk Factors for Sudden Death Within 2 Days After Diagnosis of COVID-19 in Korea.

We aimed to analyze the risk factors for sudden death after diagnosis of coronavirus disease 2019 (COVID-19) in South Korea and to provide evidence for informing prevention and control interventions for patients at risk of sudden death. We included 30,302 COVID-19 related deaths registered in the patient management information system (Central Disease Control Headquarters) between January 1, 2021, and December 15, 2022. We collected their epidemiological data recorded by the reporting city, province, or country. We performed multivariate logistic regression analysis to identify risk factors for sudden death after diagnosis of COVID-19. Among the 30,302 deaths, there were 7,258 (24.0%) and 23,044 (76.0%) sudden and non-sudden deaths, respectively. Sudden death means a person who died within 2 days of diagnosis and who did not receive inpatient treatment. Underlying condition, vaccination status, and place of death were significantly associated with the survival period in all age groups. Moreover, region, sex, and prescription were significantly associated with the survival period only in certain age groups. However, reinfection was not significantly associated with the survival period in any age group. To our knowledge, this is the first study on the risk factors for sudden death after a diagnosis of COVID-19, which included age, underlying condition, vaccination status, and place of death. Additionally, individuals aged < 60 years without an underlying condition were at high risk for sudden death. However, this group has relatively low interest in health, as can be seen from the high non-vaccination rate (16.1% of the general population vs. 61.6% of the corresponding group). Therefore, there is a possibility for the presence of an uncontrolled underlying disease in this population. In addition, many sudden deaths occurred due to delayed hospital visits to continue economic activities even after the onset of COVID-19 symptoms (7 days overall vs. 10 days average for the group). In conclusion, 'continued interest in health' is a key factor in avoiding sudden death in the economically active group (under 60 years of age).

Abstract 13783: Near-Real Time Extended Ambulatory ECG Monitoring in Patients With Syncope Unveils a Spectrum of Arrhythmias and High Incidence of Atrial Fibrillation

Introduction: Patients (pts) with a history of syncope are at high risk for sudden death with a reported 1-year mortality rate of 30%. Triaging relevant arrhythmias (ars) in a timely manner in this population is critical to allow for potential life-saving interventions. For example screening atrial fibrillation (AF) studies of pts with no known AF, reported an AF detection of 4.5% to 5.3%. It is unknown if these findings extend to a syncope population. A recent syncope study reported most significant ars occurred outside the typical window of a hospital stay. Therefore, this study aims to analyze a proprietary Zio AT database containing arrhythmia findings of pts monitored for the diagnosis of syncope. Methods: Data retrospectively analyzed 10,643 pts from US institutions with a syncope indication for monitoring. Pts with recordings between July 2017 to December 2021 were analyzed. All ars transmitted via cellular gateway during the wear period and full ECG download at end of wear were analyzed with a validated proprietary AI algorithm, then followed by a certified cardiographic technician review. Ars were defined as: AF, ≥30 seconds at any heart rate; SVT, ≥90 bpm for ≥4 S beats; Pause, ≥3 second; AV Block, any 3rd or 2nd degree AV Block (Mobitz I or II); VT, ≥100 bpm for ≥4 V beats or PVT, TdP, VF. Detected ars were characterized by duration, episode counts, rates, and/or burden (where applicable). Results: Of the 10,643 pts studied (49% female, mean age 65.4 years, mean wear 11.9 ± 3.6 days), 8,442 (79%) had at least 1 arrhythmia detected, with 3,107 (29%) having 2 or more arrhythmia types. Most common ars detected in this patient population were SVT (69%; 7365/10643), VT (26%; 2716/10643), and AF (9.5%; 1015/10643). AV Blocks (3.6%; 382/10643) and Pauses (6.2%; 662/10643) were not uncommon. Surprisingly, the most common arrhythmia to trigger a notification alert was AF/AFL (8.5%). Average time until first AF detection was 1.4 ± 2.8 days for all AF subjects and 2.8 ± 3.5 days for paroxysmal AF subjects. Conclusions: In this large retrospective study, ambulatory ECG monitoring with ZIO AT in syncope indicated pts revealed an unexpectedly high incidence of AF and SVT. Further analysis of this group may help clinicians focus a heightened awareness of atrial ars in this population.

Abstract 15004: Characterization of Hypertrophic Cardiomyopathy Caused by Mutations in Four and a Half Lim Domains 1 Gene

Background: Mutations in Four and Half Lim domain 1 ( FHL1 ), an X-chromosome gene, have been described in rare cases of Hypertrophic Cardiomyopathy (HCM), mainly associated with myopathy. The current knowledge of the outcome of HCM caused by FHL1 mutations relies only on isolated case series. Objective: We aim to establish the prevalence of FHL1 mutations in a large population with overt HCM and clinically characterize HCM patients carrying FHL1 pathogenic and likely pathogenic genetic variants. Methods: From a total population of 794 HCM patients from 3 Referral Centers for hereditary cardiomyopathies, 349 HCM probands, who tested negative for sarcomeric mutations, were genetically screened by using Next Generation Panels including FHL1 . Moreover, all patients underwent personal and family history collection, physical examination, 12-lead electrocardiogram and echocardiography; while Cardiac Magnetic Resonance (CMR) was performed in a subgroup. Clinical and genetic data of FHL1 mutation carriers from our cohort were pooled with those of 52 FHL1 positive HCM cases from literature. Results: We identified 2 FHL1 pathogenic and 2 likely pathogenic variants (1 missense: c.764G&gt;C; 2 duplications: c.762dup and c.599dupT; and 1 deletion: c.210delG) in 6 HCM probands (0.8% of all HCM and 1.7 % of non sarcomeric HCM). As shown in Fig.1 A, pooled analysis suggested that clinical phenotype of FHL1-HCM was characterized by early-onset, severe diastolic dysfunction independently from the degree of hypertrophy and fibrosis at CMR (Fig 1 B), high sudden death risk, increased incidence of atrial fibrillation and evolution toward heart failure requiring heart transplantation, and variable skeletal muscle involvement. Conclusions: HCM patients carrying FHL1 mutations present with a worse prognosis as compared with the classic sarcomeric-HCM. A better characterization of these patients is needed for a personalized preventive and therapeutic approach.

OR19-2 Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF) with Low and High Dose of Triiodothyronine: an Animal Model of Metabolic Syndrome with HFpEF

Abstract Introduction Low levels of triiodothyronine (T3) are common in patients with heart failure (HF). It has been proposed that the decreased levels of T3 contribute to metabolic and cardiac dysfunction in HF. We aimed to evaluate the effects of treatment with low dose and high dose of T3 in an animal model of HF with preserved ejection fraction (HFpEF). Materials and Methods We evaluated four groups: ZSF1 Lean (Lean-Ctrl, n=8), ZSF1 obese (rat model of metabolic syndrome with HFpEF, HFpEF-Ctrl, n=13), ZSF1 obese supplemented with a replacement dose of T3 (initially 0.04mg/ml, increased to 0.06mg/ml after 4 weeks; HFpEF-T3high, n=8), and ZSF1 Obese supplemented with a low-dose of T3 (0.03mg/mL; HFpEF-T3low, n=8). T3 was supplemented in drinking water from week 13 to 24. The animals were submitted to anthropometric and metabolic evaluation, echocardiography, VO2max evaluation, hemodynamic evaluation, single cardiomyocyte evaluation, and myocardial tissue collection at 24 weeks. Results HFpEF-Ctrl animals had lower serum and myocardial thyroid hormone levels than Lean-Ctrl. Treatment with low dose and high dose of T3 did not correct serum T3 levels, but increased myocardial T3 levels, with normalization of myocardial T3 levels in the HFpEF-T3high group. In comparison to HFpEF-Ctrl, body weight was significantly decreased in HFpEF-T3low and HFpEF-T3high groups (616±39g, 572±24g and 535±18g respectively, p&amp;lt;0.001). An improvement in glucose metabolism was observed only in HFpEF-T3high, with a decreased AUC of glucose during OGTT and insulin tolerance test. Both treated groups presented an improvement in diastolic function (with decreased isovolumetric relaxation time) and systolic function (with increased peak systolic velocity and decreased ejection time) comparing to HFpEF-Ctrl. These results were supported by enhanced Ca2+ transients during diastole and sarcomere relaxation. Comparing with HFpEF-Ctrl, animals treated with T3 had higher myocardial expression of the calcium transporter RYR2, of the transcriptional coactivator PGC-1α, and of the α-myosin heavy chain (MHC), with a lower expression of β-MHC. VO2max was improved with low-dose and high-dose T3 compared with HFpEF-Ctrl. Comparing with HFpEF-Ctrl, heart rate was increased with high-dose (277.9±30.2 vs 313.5±35.8, p=0.049) but not significantly with low-dose (277.9±30.2 vs 299.8±30.9 bpm, p=0.13). Mortality was increased in the HFpEF-T3high comparing with the other groups (no animals died during the protocol in the Lean-Ctrl, HFpEF-Ctrl and HFpEF-T3low groups; three animals had sudden death in the HFpEF-T3high group). Conclusion Treatment with T3 improves metabolic function, myocardial calcium handling, diastolic and systolic function, and exercise capacity in this animal model of HFpEF. While the low dose was well tolerated and safe, the high dose was associated with increased heart rate and a higher risk of sudden death. Modulation of thyroid hormones may be a potential therapeutic target in HFpEF; however such approaches must take into account a narrow therapeutic window of T3 in HFpEF. Presentation: Monday, June 13, 2022 11:15 p.m. - 11:30 a.m.

Using machine learning to find genes associated with sudden death.

To search for significant biomarkers associated with sudden death (SD). Differential genes were screened by comparing the whole blood samples from 15 cases of accidental death (AD) and 88 cases of SD. The protein-protein interaction (PPI) network selects core genes that interact most frequently. Machine learning is applied to find characteristic genes related to SD. The CIBERSORT method was used to explore the immune-microenvironment changes. A total of 10 core genes (MYL1, TNNC2, TNNT3, TCAP, TNNC1, TPM2, MYL2, TNNI1, ACTA1, CKM) were obtained and they were mainly related to myocarditis, hypertrophic myocarditis and dilated cardiomyopathy (DCM). Characteristic genes of MYL2 and TNNT3 associated with SD were established by machine learning. There was no significant change in the immune-microenvironment before and after SD. Detecting characteristic genes is helpful to identify patients at high risk of SD and speculate the cause of death.