Lesions of the Cardiac Conduction System and Sudden Death.

ABSTRACT: When a young previously healthy person dies suddenly, occasionally, the scene is noncontributory and the autopsy and drug screen are negative. In such cases, additional studies, including genetic assessment and cardiac conduction system examination, should be performed. We performed a literature search and reviewed our own material to identify possible or definite conduction system anomalies that may cause death. We identified intrinsic conduction system disease including cystic tumor of the atrioventricular node, atrioventricular node (cystic tumor of the AV node), and fibromuscular dysplasia of the atrioventricular node artery to be likely causes of death. Extrinsic causes, in which a generalized disease affects the conduction system, include tumors, autoimmune disease, infiltrative disorders, and others, are a second category of diseases that can affect the conduction system and cause atrioventricular block and sudden death.

Lack of evidence for longitudinal dissociation of the atrioventricular conduction axis.

Longitudinal dissociation of the aggregated specialized cardiomyocytes within the non-branching portion of atrioventricular conduction axis has proved a controversial topic for both morphologists and electrophysiologists. We have now used morphological methods, including three-dimensional assessment, to revisit, in human, canine, and bovine hearts, the presence or absence of interconnections between the aggregated cardiomyocytes making up the non-branching bundle. We analyzed three datasets from human and canine hearts, and two from bovine hearts, using longitudinal and orthogonal serial histological sections. In addition, we assessed three hearts using translucent India ink injected specimens, permitting assessment of the three-dimensional arrangement of the cardiomyocytes. Using the longitudinal sections, we found numerous oblique interconnections between the groups of specialized cardiomyocytes. When assessing orthogonal sections, we noted marked variation in the grouping of the cardiomyocytes. We interpreted this finding as evidence of bifurcation and convergence of the groups seen in the longitudinal sections. The three-dimensional assessment of the bovine material confirmed the presence of the numerous interconnections. The presence of multiple connections between the cardiomyocytes in the non-branching bundle rules out the potential for longitudinal dissociation.

Sex-dependent expression of prostatic markers and hormone receptors in cystic tumor of the atrioventricular node: A histopathological study of three cases.

We pathologically investigated three autopsy cases of cystic tumor of the atrioventricular node (CTAVN) with sudden death. Case 1 was a 36-year-old woman without any clinical history. Case 2 was a 76-year-old man with an implanted pacemaker for complete atrioventricular block. Case 3 was a 45-year-old man with a history of first-degree AV block and sinus bradycardia. Microscopically, all three cases showed the bilayered structure of tumor glands and corpora amylacea in the glandular lumens. Immunohistochemically, the inner cells of the tumor glands were positive for cytokeratin CAM5.2, CEA, EMA, olfactomedin-4 and alpha-methylacyl-coenzyme A racemase; the outer cells were positive for p63 and cytokeratin high molecular weight. In Case 1, androgen receptor and estrogen receptor were negative; progesterone receptor was focally positive in both the inner and outer cells. In Case 2, androgen receptor showed intermediate positivity in the inner cells; estrogen receptor and progesterone receptor were positive in the outer cells. Positive expression of both prostate-specific antigen and prostate-specific acid phosphate were found in the inner cells of both male cases. Because CTAVN cells exhibit different degrees of the prostatic phenotype depending on the patient's sex, we believe that CTAVN may originate from urogenital sinus tissue in some cases.

Knockout of tnni1b in zebrafish causes defects in atrioventricular valve development via the inhibition of the myocardial wnt signaling pathway.

The proper development of atrioventricular (AV) valves is critical for heart morphogenesis and for the formation of the cardiac conduction system. Defects in AV valve development are the most common type of congenital heart defect. Cardiac troponin I ( ctnni), a structural and regulatory protein involved in cardiac muscle contraction, is a subunit of the troponin complex, but the functions and molecular mechanisms of ctnni during early heart development remain unclear. We created a knockout zebrafish model in which troponin I type 1b ( tnni1b) ( Tnni-HC, heart and craniofacial) was deleted using the clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat-associated protein system. In the homozygous mutant, the embryos showed severe pericardial edema, malformation of the heart tube, reduction of heart rate without contraction and with almost no blood flow, heart cavity congestion, and lack of an endocardial ring or valve leaflet, resulting in 88.8 ± 6.0% lethality at 7 d postfertilization. Deletion of tnni1b caused the abnormal expression of several markers involved in AV valve development, including bmp4, cspg2, has2, notch1b, spp1, and Alcam. Myocardial re-expression of tnni1b in mutants partially rescued the pericardial edema phenotype and AV canal (AVC) developmental defects. We further showed that tnni1b knockout in zebrafish and ctnni knockdown in rat h9c2 myocardial cells inhibited cardiac wnt signaling and that myocardial reactivation of wnt signaling partially rescued the abnormal expression of AVC markers caused by the tnni1b deletion. Taken together, our data suggest that tnni1b plays a vital role in zebrafish AV valve development by regulating the myocardial wnt signaling pathway.-Cai, C., Sang, C., Du, J., Jia, H., Tu, J., Wan, Q., Bao, B., Xie, S., Huang, Y., Li, A., Li, J., Yang, K., Wang, S., Lu, Q. Knockout of tnni1b in zebrafish causes defects in atrioventricular valve development via the inhibition of myocardial wnt signaling pathway.

Cartilaginous Metaplasia Involving the Atrioventricular Node and Bundle of His Contributing to Sudden Early Neonatal Death.

Cartilaginous metaplasia involving the atrioventricular (AV) node is an uncommon entity that may cause sudden cardiac death secondary to dysrhythmias. We report 2 autopsy cases of full-term male newborns: 1 stillborn and 1 live-born, with antemortem bradycardia who died in the peripartum period. An examination of the cardiac conduction system in both cases demonstrated extensive cartilaginous metaplasia of the central fibrous body and involvement of the AV node and bundle of His. The cases highlight the recognition of cardiac conduction system anomalies as a cause of sudden perinatal death. In cases of perinatal death with preceding arrhythmia, postmortem sections of the cardiac conduction system are recommended to examine for cardiac conduction system anomaly.

Sudden Death Due to Cystic Tumor of the Atrioventricular Node and Fibromuscular Dysplasia Involving Branches of the Coronary Arteries.

In this paper, we report the autopsy findings of a 42-year-old White male who was found deceased at his home by his brother in the early morning hours with a history of excessive alcohol consumption 1 day before his death. A medical record review revealed chronic alcohol use with alcohol dependence syndrome, hypertension, and cardiac arrhythmias by electrocardiogram 2 years prior. External examination revealed only a single bruise on the forehead. Internal examination revealed changes associated with chronic alcohol abuse and mild atherosclerosis. The lack of a cause of death at autopsy resulted in a dissection of the cardiac conduction system and the detection of a small cystic lesion at the atrioventricular node region. Microscopic examination revealed a cystic tumor of the atrioventricular node and fibromuscular dysplasia of the coronary artery branches near the sinoatrial and atrioventricular nodes. Based on the case history and autopsy findings, death was attributed to a fatal cardiac arrhythmia due to cystic tumor of the atrioventricular node with fibromuscular dysplasia of the coronary artery branches near the sinoatrial and atrioventricular nodes a possible contributing factor.

[Sudden cardiac death due to sarcoidosis. Case report]. / Hirtelen szívhalál sarcoidosis következtében.

Sarcoidosis is a systemic granulomatous disease of unknown aetiology, which is characterized by bilateral hilar lymphadenopathy and pulmonary disease. Clinically detected cardiac involvement occurs in 5% of sarcoid patients, although cardiac manifestations are discovered in 25% of the cases at autopsy. Sarcoid heart disease frequently causes atrioventricular block. The authors present the case of a 44-year-old man with bradycardia. On admission, second degree Mobitz II, then third degree atrioventricular block was diagnosed. Coronarography showed normal coronary arteries. 2.5 years following artificial Biotronik Entovis DR type pacemaker implantation, sudden cardiac death occurred. Autopsy revealed sarcoidosis with cardiac, pulmonary, splenic, renal and lymph node involvement. In case of young or middle-aged patients with atrioventricular block, it is best to search for other causes if the most common coronary origin can be excluded. Orv Hetil. 2017; 158(27): 1067-1070.

Automated quantitative assessment of cardiovascular magnetic resonance-derived atrioventricular junction velocities.

The assessment of atrioventricular junction (AVJ) deformation plays an important role in evaluating left ventricular systolic and diastolic function in clinical practice. This study aims to demonstrate the effectiveness and consistency of cardiovascular magnetic resonance (CMR) for quantitative assessment of AVJ velocity compared with tissue Doppler echocardiography (TDE). A group of 145 human subjects comprising 21 healthy volunteers, 8 patients with heart failure, 17 patients with hypertrophic cardiomyopathy, 52 patients with myocardial infarction, and 47 patients with repaired Tetralogy of Fallot were prospectively enrolled and underwent TDE and CMR scan. Six AVJ points were tracked with three CMR views. The peak systolic velocity (Sm1), diastolic velocity during early diastolic filling (Em), and late diastolic velocity during atrial contraction (Am) were extracted and analyzed. All CMR-derived septal and lateral AVJ velocities correlated well with TDE measurements (Sm1: r = 0.736; Em: r = 0.835; Am: r = 0.701; Em/Am: r = 0.691; all p < 0.001) and demonstrated excellent reproducibility [intrastudy: r = 0.921-0.991, intraclass correlation coefficient (ICC): 0.918-0.991; interstudy: r = 0.900-0.970, ICC: 0.887-0.957; all p < 0.001]. The evaluation of three-dimensional AVJ motion incorporating measurements from all views better differentiated normal and diseased states [area under the curve (AUC) = 0.918] and provided further insights into mechanical dyssynchrony diagnosis in HF patients (AUC = 0.987). These findings suggest that the CMR-based method is feasible, accurate, and consistent in quantifying the AVJ deformation, and subsequently in diagnosing systolic and diastolic cardiac dysfunction.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

BACKGROUND: Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. METHODS: Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. RESULTS: Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. CONCLUSION: Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN.

Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis.

TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood. We tested the requirements for Tbx3 in these processes. We generated a unique series of Tbx3 hypomorphic and conditional mouse mutants with varying levels and locations of Tbx3 activity within the heart, and developed techniques for evaluating in vivo embryonic conduction system function. Disruption of Tbx3 function in different regions of the developing heart causes discrete phenotypes and lethal arrhythmias: sinus pauses and bradycardia indicate sinoatrial node dysfunction, whereas preexcitation and atrioventricular block reveal abnormalities in the atrioventricular junction. Surviving Tbx3 mutants are at increased risk for sudden death. Arrhythmias induced by knockdown of Tbx3 in adults reveal its requirement for conduction system homeostasis. Arrhythmias in Tbx3-deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers. These findings indicate that Tbx3 is required for the conduction system to establish and maintain its correct molecular identity and functional properties. In conclusion, Tbx3 is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner. TBX3 and its regulatory targets merit investigation as candidates for human arrhythmias.

Surgical palliation strategy does not affect interstage ventricular dysfunction or atrioventricular valve regurgitation in children with hypoplastic left heart syndrome and variants.

BACKGROUND: All 3 palliation strategies, Norwood, Sano, and Hybrid, currently used for hypoplastic left heart syndrome pose a risk of myocardial injury at different times and through different mechanisms. We sought to compare these strategies to understand longitudinal differences in interstage ventricular dysfunction and their subsequent impact on transplant-free survival and atrioventricular valve regurgitation (AVVR) as well as the relationship between adverse events and ventricular function. METHODS AND RESULTS: Serial echocardiographic reports and clinical data were reviewed for 138 children with hypoplastic left heart syndrome who underwent stage I surgical palliation (Sano: 11; Norwood: 73; Hybrid: 54) between 2004 and 2011. Stage II palliation was achieved in 92 (67%) patients (Sano: 7; Norwood: 51; Hybrid: 34). Interstage transplant-free survival, ventricular dysfunction, and AVVR were equivalent among palliation strategies. Patients with preserved ventricular function had a higher rate of transplant-free survival and freedom from AVVR, regardless of palliation strategy. Patients who had cardiac arrest, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation (adverse events) experienced more transient and persistent ventricular dysfunction compared to those without adverse events. Surgical palliation strategies were not identified as risk factors for ventricular dysfunction or AVVR. CONCLUSIONS: Surgical palliation strategy does not affect mortality, interstage ventricular function, or interstage AVVR in children with hypoplastic left heart syndrome. Therefore, the different timing and mechanisms of myocardial injury among palliation strategies do not affect outcomes. Ventricular dysfunction adversely affects transplant-free survival and atrioventricular valve function. Adverse events are associated with the development of ventricular dysfunction. To improve outcomes, interstage treatment should focus on the preservation of ventricular function.

Sudden cardiac death due to arrhythmogenic right ventricular cardiomyopathy and cystic tumor of the AV node.

An 18-year-old white male collapsed suddenly in his home and died. At autopsy, the right ventricle of the decedent was noted to be dilated with marked thinning of the wall focally. Microscopically, the myocardium of the right ventricle was noted to be significantly thinned focally, where transmural infiltration with fibroadipose tissue was noted. Depending on the criteria utilized to render such a diagnosis, these findings were consistent with arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequent microscopic examination of the SA and AV node, however, revealed the presence of a cystic tumor of the AV node (CTAVN), a known cause of sudden death from arrhythmia. The case represents the first reported case of ARVC and CTAVN occurring together in the same individual.

Genetic suppression of Gαs protein provides rate control in atrial fibrillation.

Gene therapy-based modulation of atrioventricular (AV) conduction by overexpression of a constitutively active inhibitory Gα(i) protein effectively reduced heart rates in atrial fibrillation (AF). However, catecholamine stimulation caused an excessive increase in ventricular rate. We hypothesized that modest genetic suppression of a stimulatory G protein in the AV node would allow persistent rate control in acute AF and would prevent undesired heart rate acceleration during ß-adrenergic activation. Atrial fibrillation was induced in 12 pigs by atrial burst pacing via an implanted cardiac pacemaker. Study animals were then assigned to receive either Ad-siRNA-Gα(s) gene therapy to inactivate Gα(s) protein or Ad-ß-gal as control. Gα(s) protein inactivation resulted in a 20 % heart rate reduction (P < 0.01). AH and HV intervals were prolonged by 37 ms (P < 0.001) and 28 ms (P < 0.001), respectively, demonstrating atrioventricular conduction delay. Impairment of left ventricular ejection fraction (LVEF) during AF was attenuated by Gα(s) suppression (LVEF 49 %) compared with controls (LVEF 34 %; P = 0.03). Isoproterenol application accelerated ventricular heart rate from 233 to 281 bpm (P < 0.001) in control animals but did not significantly affect pigs treated with Ad-siRNA-Gα(s) (192 vs. 216 bpm; P = 0.19). In conclusion, genetic inhibition of Gα(s) protein in the AV node reduced heart rate and prevented AF-associated reduction of cardiac function in a porcine model. Rate control by gene therapy may provide an alternative to current pharmacological treatment of AF.

Atrioventricular conduction delay in fetuses exposed to anti-SSA/Ro and anti-SSB/La antibodies: a magnetocardiography study.

BACKGROUND: The presence of anti-SSA/Ro and anti-SSB/La antibodies during pregnancy is associated with fetal congenital heart block (CHB), which is primarily diagnosed through fetal echocardiography. Conclusive information about the complete electrophysiology of the fetal cardiac conducting system is still lacking. In addition to echocardiography, fetal magnetocardiography (fMCG) can be used. fMCG is the magnetic analogue of the fetal electrocardiogram (ECG). PATIENTS AND METHODS: Forty-eight pregnant women were enrolled in an observational study; 16 of them tested positive for anti-SSA/Ro and anti-SSB/La antibodies. In addition to routine fetal echocardiography, fMCG was used. Fetal cardiac time intervals (fCTIs) were extracted from the magnetic recordings by predefined procedures. ECGs in the neonates of the study group were performed within the first month after delivery. RESULTS: The PQ segment of the fCTI was significantly prolonged in the study group (P = 0.007), representing a delay of the electrical impulse in the atrioventricular (AV) node. Other fCTIs were within normal range. None of the anti-SSA/Ro and/or anti-SSB/La fetuses progressed to a more advanced heart block during pregnancy or after birth. CONCLUSION: The study identified a low-risk population within antibody positive mothers, where PQ segment prolongation is associated with a lack of progression of the disease.

Age-related histopathological changes in the cardiac conducting system in the Turkish population: an evaluation of 202 autopsy cases.

BACKGROUND: Histopathological features of the cardiac conducting system (CCS) in the Turkish population have not been investigated previously. MATERIAL AND METHODS: We examined CCS of 202 autopsy heart specimens dissected between the years 2004 and 2005 in Bursa Forensic Medicine Institution. Of the 202 cases from all age groups, 154 were males and 48 were females. RESULTS: In our cases, an increase in fibrous and adipose tissue concordant with age, indicating an age-related nature, were detected. Fibrous and fatty tissue infiltration appeared at the age of 35. Fatty infiltration started between the ages 20 and 34 years at the sinoatrial node (SAN). There was no relationship between obesity and fatty tissue infiltration in SAN and atrioventricular node (AVN). In 4 cases calcification and in 19 cases inflammation was observed. Amyloid accumulation was not present. In 7 cases myocardial infarction not involving CCS was seen. In 1 case fibroelastoma was detected. CONCLUSIONS: In the Turkish population age-related fibrosis and fatty infiltration in CCS appeared at the age of 35 years and increased with age. Fatty infiltration in the SAN started at a younger age than that reported in the literature. In cases where the cause of death could not be determined, we could not detect lethal pathological features. However, we think that examination of the CCS will improve the quality of autopsy diagnosis.

Development of an ovine model of pediatric complete heart block.

BACKGROUND: Complete heart block is a significant clinical problem that can limit the quality of life in affected children. To understand the pathophysiology of this condition and provide for development of novel therapies, we sought to establish a large animal model of permanent, pacemaker-dependent atrioventricular block (AVB) that mimics the size and growth characteristics of pediatric patients. MATERIALS AND METHODS: We utilized nine immature lambs weighing 10.5 ± 1.4 kg. After implantation of dual-chamber pacemaker devices with fixed leads, AVB was produced by interrupting His-bundle conduction using radio-frequency ablation at the base of the non-coronary cusp of the aortic valve. Ablations (30 to 60 s in duration) were performed under fluoroscopic guidance with electrophysiological monitoring. Interrogation of pacemakers and electrocardiography (ECG) determined the persistence of heart block. Ovine hearts were also examined immunohistochemically for localization of conduction tissue. RESULTS: AVB was produced in eight animals using an atypical approach from the left side of the heart. One animal died due to ventricular fibrillation during ablation proximal to the tricuspid annulus and one lamb was sacrificed postoperatively due to stroke. Four sheep were kept for long-term follow-up (109.8 ± 32.9 d) and required continuous ventricular pacing attributable to lasting AVB, despite significant increases in body weight and size. CONCLUSIONS: We have created a large animal model of pediatric complete heart block that is stable and technically practicable. We anticipate that this lamb model will allow for advancement of cell-based and other innovative treatments to repair complete heart block in children.

Cystic tumour of the atrioventricular node: three cases of sudden death.

Cystic tumour of the atrioventricular nodal region is a rare primary cardiac tumour that can cause sudden death. Antemortem diagnosis and successful excision of this type of tumour are extremely rare. Three cases of sudden death are reported: A 25- and 40-year-old with a history of heart block and a 60-year-old with no medical history. There have been more than 120 cases of sudden death attributed to primary cardiac tumours in the literature. Although over 100 of these lesions were histologically benign, their intracardiac locations precipitated conductive and haemodynamic abnormalities that resulted in sudden death. The most common intracardiac lesion causing sudden death, cystic tumour of the atrioventricular node, however, may not be discovered unless the atrioventricular node is microscopically examined.

Primary breast lymphoma with sudden death.

Primary breast lymphoma is a rare form of extranodal lymphoma. B cells constitute the most common type involving the breast. T cells represents only 3%. Even though lymphomas have a high predilection to metastasize to the heart, there are no specific clinical or radiological findings, and most of the cases are diagnosed at autopsy. We discuss the case of a 49-year-old woman with primary breast lymphoma who presented with sudden death. Autopsy revealed a primary T-cell lymphoma of the breast with tumoral infiltration of the atrioventricular node and transmural myocardial permeation with focal necrosis.

[Echocardiographic parameters in patients with Wolf-Parkinson-White syndrome before and during one year after radiofrequency catheter ablation of accessory atrioventricular junction].

We present in this paper results of assessment of morphofunctional state of myocardium in patients with the Wolf-Parkinson-White syndrome before and during one year after radiofrequency catheter ablation (RFA) of accessory atrioventricular junction (AAVJ) and comparison of them with analogous parameters of the group of healthy volunteers as well as in dependence on electrophysiological properties of AAVJ and its localization. One hundred sixty patients took part in the conducted study: main group comprised 160 patients (80.7%) with WPW syndrome (114 men [81.4%], 26 women [18.6%], mean age 39.5+/-15.3 years), comparison group comprised 20 practically healthy persons (15 men [75.0%], 5 women [25%], mean age 41.9+/-5.3 years). All main group patients were subjected to endocardial electrophysiological investigation and RFA of AAVJ. Transthoracic echocardiography (EchoCG) was carried out in patients of main group before and in 2, 6, and 12 months after operation of RFA of AAVJ, and once in control group. Analysis of parameters of central hemodynamics according to data of transthoracic EchoCG in patients with WPW syndrome before RFA of AAVJ demonstrated that before conduct of operative intervention no significant differences were revealed in the studied parameters compared with analogous characteristics of the clinical comparison group. During whole period of dynamic observation (2, 6, and 12 months after fulfilled RFA of AAVJ) in patients with WPW syndrome the studied parameters of central hemodynamics did not undergo substantial changes compared with initial characteristics. We failed to establish significant differences of EchoCG parameters in patients with WPW syndrome in dependence on electrophysiological properties of AAVJ (concealed, manifest) and on AAVJ localization (right, left, septal). According to EchoCG data in patients with WPW syndrome so called "minor" anomalies of development of connective tissue of the heart were diagnosed in 69 (49.3%) patients while in control group - in 2 (10%) patients.

Sudden Unexpected Death Due to Myocarditis in Young People, Including Athletes.

Sudden deaths in young active people and athletes are distinctly uncommon and frequently related to highly visible cardiovascular conditions including hypertrophic cardiomyopathy and congenital coronary anomalies. Myocarditis is also a cause of sudden death in the young, but frequently under-recognized clinically, and therefore deserving of the present analysis. Two large registries were interrogated for cases of myocarditis, and clinical, demographic, and pathologic findings were assessed. Of 97 cases of myocarditis identified, ages were 19.3 ± 6.2 years, 76% male, and 58 were physically active at or near the time of death. Almost one-half of the 97 cases (47%) had a viral prodrome or symptoms (i.e., syncope, malaise, chest pain or palpitations). Nine were evaluated by cardiologists, but in none was a diagnosis of myocarditis established before death. The inflammatory cellular infiltrate was predominantly lymphocytic (67%), was most frequently multifocal (59%) and involved the conduction system (including atrioventricular node), 38%. In conclusion, myocarditis is an important but under-recognized cause of sudden death in young people including competitive athletes. Clinical diagnosis is difficult because symptoms are nonspecific and often ignored, requiring high index of suspicion for diagnosis. Our data support the ACC/AHA consensus guidelines recommending removal of individuals with myocarditis from competitive sports during recovery. Selective examination of conduction systems showed a number of cases with involvement of myocarditis, suggesting a novel mechanism for sudden death.