Echocardiographic Findings in Children of Patients Diagnosed with PRKAG2 Syndrome. / Achados Ecocardiográficos em Crianças de Pacientes com Diagnóstico de Síndrome do PRKAG2.

BACKGROUND: PRKAG2 syndrome typically manifests in adolescence and early adulthood, progressing with left ventricular hypertrophy, arrhythmias, and risk of sudden death. Findings of echocardiographic markers before clinical manifestation in children of patients affected by the disease can facilitate prevention strategies and therapeutic planning for this patient group. OBJECTIVE: To identify the existence of echocardiographic findings that manifest early in children of parents affected by PRKAG2 syndrome, while they are still asymptomatic. METHODS: In this cross-sectional observational study, 7 participants who were children of parents with established diagnosis of PRKAG2 syndrome, between the ages of 9 months and 12 years, with proven genetic diagnosis, underwent conventional and advanced echocardiography. Their findings were compared to those of a control group composed of 7 age- and sex-matched volunteers who were healthy from a cardiovascular point of view. P values < 0.05 were considered significant. RESULTS: Conventional echocardiography showed statistically significantly higher values in the case group for left atrium, interventricular septum, left ventricular posterior wall, indexed ventricular mass, and relative wall thickness (p < 0.05). Global longitudinal systolic strain on 2-dimensional echocardiography did not show statistical significance between the case and control groups. None of the parameters on 3-dimensional echocardiography showed statistical significance between groups. CONCLUSION: Children diagnosed with PRKAG2 showed echocardiographic findings indicative of a tendency toward cardiac hypertrophy. Echocardiography can be a useful tool in the evaluation and follow-up of this patient group before the onset of clinical manifestations.

FUNDAMENTO: A síndrome do PRKAG2 tipicamente se manifesta na adolescência e início da idade adulta, cursando com hipertrofia ventricular esquerda, arritmias e risco de morte súbita. O achado de marcadores ecocardiográficos antes da manifestação clínica nos filhos de pais acometidos pela doença pode facilitar a estratégia de prevenção e planejamento terapêutico para esse grupo de pacientes. OBJETIVO: Identificar a existência de achados ecocardiográficos que se manifestem precocemente nos filhos de pais acometidos por síndrome do PRKAG2, enquanto ainda assintomáticos. MÉTODOS: Estudo observacional transversal em que sete participantes, filhos de pais com diagnóstico estabelecido de síndrome do PRKAG2, com idades entre 9 meses e 12 anos e diagnóstico genético comprovado, foram submetidos à ecocardiografia convencional e por técnicas avançadas, tendo seus achados comparados aos de grupo controle composto por sete voluntários pareados por sexo e idade, hígidos do ponto de vista cardiovascular. Um valor de p < 0,05 foi considerado significante. RESULTADOS: A ecocardiografia convencional mostrou valores aumentados com significância estatística no grupo caso para átrio esquerdo, septo interventricular, parede posterior do ventrículo esquerdo, massa ventricular indexada e espessura relativa da parede (p < 0,05). O strain sistólico longitudinal global obtido pelo ecocardiograma bidimensional não mostrou diferença estatisticamente significativa entre os grupos caso e controle. Nenhum dos parâmetros ao ecocardiograma tridimensional apresentou significância estatística entre os grupos. CONCLUSÃO: Crianças diagnosticadas com PRKAG2 demonstraram achados ecocardiográficos indicativos de tendência à hipertrofia cardíaca. A ecocardiografia pode ser uma ferramenta útil na avaliação e seguimento desse grupo de pacientes, antes do início de manifestações clínicas.

Evidence for concealed fasciculo-ventricular connections as revealed by His bundle pacing.

BACKGROUND: It is almost 100 years ago since Mahaim described the so-called paraspecific connections between the ventricular conduction axis and the crest of the muscular ventricular septum, believing such pathways to be ubiquitous. These pathways, however, have yet to be considered as potential pathways for septal activation during His bundle pacing. MATERIALS: So as to explore the hypothesis that specialised septal pathways might provide the substrate for septal activation during His bundle pacing, we compared the findings from 22 serially sectioned histological datasets and 34 different individuals undergoing His bundle pacing. RESULTS: We found histologically specialised pathways connecting the branching component of the atrioventricular conduction axis with the crest of the muscular ventricular septum in almost four-fifths of the histological datasets. In 32 of 34 patients undergoing His bundle pacing, the QRS complex closely resembled published images of known conduction through fasciculo-ventricular pathways. In only two patients was a delta wave not seen at any pacing voltages. Capture of these connections varied according to pacing voltage, a finding which correlated with the distance of the pathways from the site of penetration of the ventricular conduction axis. Ventricular activation times remained normal in the presence of the delta wave at higher pacing voltage but were prolonged at lower voltages. CONCLUSIONS: Our histologic findings confirm fasciculo-ventricular connections, initially described by Mahaim as being paraspecific, are likely ubiquitous. Analysis of 12-lead electrocardiograms leads us to conclude that fasciculo-ventricular pathways, concealed during sinus rhythm, become manifest with His bundle pacing.

Confounding factors leading to misdiagnosing ventricular tachycardia as supraventricular in the emergency room.

Studies conducted during the last 50 years have proposed electrocardiographic criteria and algorithms to determine if a wide QRS tachycardia is ventricular or supraventricular in origin. Sustained ventricular tachycardia is an uncommon reason for consultation in the emergency room. The latter and the complexity of available electrocardiographic diagnostic criteria and algorithms result in frequent misdiagnoses. Good hemodynamic tolerance of tachycardia in the supine position does not exclude its ventricular origin. Although rare, ventricular tachycardia in patients with and without structural heart disease may show a QRS duration <120 ms. Interruption of tachycardia by coughing, carotid sinus massage, Valsalva maneuver, or following the infusion of adenosine or verapamil should not discard the ventricular origin of the arrhythmia. In patients with regular, uniform, sustained broad QRS tachycardia, the presence of structural heart disease or A-V dissociation strongly suggest its ventricular origin. Occasionally, ventricular tachycardia can present with AV dissociation without this being evident on the 12-lead ECG. Cardiac auscultation, examination of the jugular venous pulse, and arterial pulse palpation provide additional clues for identifying A-V dissociation during tachycardia. This paper does not review the electrocardiographic criteria for categorizing tachycardia as ventricular but rather why emergency physicians misdiagnose these patients.

Acometimento do Ventrículo Direito na Cardiomiopatia por Depósito de Glicogênio (PRKAG2): Análise Ecocardiográfica Convencional e Avançada / Right Ventricle Involvement by Glycogen Storage Cardiomyopathy (PRKAG2): Standard and Advanced Echocardiography Analyses

Resumo Fundamento A síndrome do PRKAG2 é uma doença hereditária autossômica dominante rara, de início precoce. Objetivamos descrever os achados ecocardiográficos do ventrículo direito (VD) usando modalidades bi e tridimensionais (2D e 3D), incluindo índices de deformação miocárdica nesta cardiomiopatia. Também objetivamos demonstrar se esta técnica poderia identificar alterações na função do VD que pudessem distinguir quaisquer achados particulares. Métodos Trinta pacientes com síndrome do PRKAG2 (R302Q e H401Q) geneticamente comprovada, 16 (53,3%) do sexo masculino, com idade média de 39,1 ± 15,4 anos, foram submetidos a exame ecocardiográfico completo. A visão de 4 câmaras com foco no VD foi adquirida para medições 2D e 3D. Os testes t de Student ou Wilcoxon-Mann-Whitney foram usados para comparar as variáveis numéricas entre 2 grupos, e p < 0,05 foi considerado significativo. Resultados Doze pacientes (40%) tiveram marca-passo implantado por 12,4 ± 9,9 anos. A espessura diastólica média da parede livre do VD foi de 7,9 ± 2,9 mm. O strain longitudinal de 4 câmaras do VD (SL4VD), incluindo a parede livre e o septo interventricular, foi de -17,3% ± 6,7%, e o strain longitudinal da parede livre do VD (SLPLVD) foi de −19,1% ± 8,5%. A razão apical do SLPLVD mediu 0,63 ± 0,15. A fração de ejeção (FE) 3D média do VD foi de 42,6% ± 10,9% e abaixo dos limites normais em 56,7% dos pacientes. Correlação positiva ocorreu entre FE 3D do VD, SL4VD e SLPLVD, principalmente para pacientes sem marca-passo (p = 0,006). Conclusão O envolvimento do VD em PRKAG2 é frequente e ocorre em diferentes graus. A ecocardiografia é uma ferramenta valiosa na detecção de anormalidades miocárdicas do VD nesta condição. O uso de SL4VD 2D, SLPLVD e FE 3D oferecem indicadores confiáveis de disfunção sistólica do VD nesta cardiomiopatia rara e desafiadora.

Abstract Background PRKAG2 syndrome is a rare, early-onset autosomal dominant inherited disease. We aimed to describe the right ventricle (RV) echocardiographic findings using two and three-dimensional (2D and 3D) modalities including myocardial deformation indices in this cardiomyopathy. We also aimed to demonstrate whether this technique could identify changes in RV function that could distinguish any particular findings. Methods Thirty patients with genetically proven PRKAG2 (R302Q and H401Q), 16 (53.3%) males, mean age 39.1 ± 15.4 years, underwent complete echocardiography examination. RV-focused, 4-chamber view was acquired for 2D and 3D measurements. Student's t or Wilcoxon-Mann-Whitney tests were used to compare numerical variables between 2 groups, and p < 0.05 was considered significant. Results Twelve patients (40%) had a pacemaker implanted for 12.4 ± 9.9 years. RV free wall mean diastolic thickness was 7.9 ± 2.9 mm. RV 4-chamber longitudinal strain (RV4LS), including the free wall and interventricular septum, was -17.3% ± 6.7%, and RV free wall longitudinal strain (RVFWLS) was −19.1% ± 8.5%. The RVFWLS apical ratio measured 0.63 ± 0.15. Mean RV 3D ejection fraction (EF) was 42.6% ± 10.9% and below normal limits in 56.7% of patients. Positive correlation occurred between RV 3DEF, RV4LS, and RVFWLS, especially for patients without a pacemaker (p = 0.006). Conclusion RV involvement in PRKAG2 syndrome is frequent, occurring in different degrees. Echocardiography is a valuable tool in detecting RV myocardial abnormalities in this condition. The use of 2D RV4LS, RVFWLS, and 3DEF offers reliable indicators of RV systolic dysfunction in this rare, challenging cardiomyopathy.

Right Ventricle Involvement by Glycogen Storage Cardiomyopathy (PRKAG2): Standard and Advanced Echocardiography Analyses. / Acometimento do Ventrículo Direito na Cardiomiopatia por Depósito de Glicogênio (PRKAG2): Análise Ecocardiográfica Convencional e Avançada.

BACKGROUND: PRKAG2 syndrome is a rare, early-onset autosomal dominant inherited disease. We aimed to describe the right ventricle (RV) echocardiographic findings using two and three-dimensional (2D and 3D) modalities including myocardial deformation indices in this cardiomyopathy. We also aimed to demonstrate whether this technique could identify changes in RV function that could distinguish any particular findings. METHODS: Thirty patients with genetically proven PRKAG2 (R302Q and H401Q), 16 (53.3%) males, mean age 39.1 ± 15.4 years, underwent complete echocardiography examination. RV-focused, 4-chamber view was acquired for 2D and 3D measurements. Student's t or Wilcoxon-Mann-Whitney tests were used to compare numerical variables between 2 groups, and p < 0.05 was considered significant. RESULTS: Twelve patients (40%) had a pacemaker implanted for 12.4 ± 9.9 years. RV free wall mean diastolic thickness was 7.9 ± 2.9 mm. RV 4-chamber longitudinal strain (RV4LS), including the free wall and interventricular septum, was -17.3% ± 6.7%, and RV free wall longitudinal strain (RVFWLS) was -19.1% ± 8.5%. The RVFWLS apical ratio measured 0.63 ± 0.15. Mean RV 3D ejection fraction (EF) was 42.6% ± 10.9% and below normal limits in 56.7% of patients. Positive correlation occurred between RV 3DEF, RV4LS, and RVFWLS, especially for patients without a pacemaker (p = 0.006). CONCLUSION: RV involvement in PRKAG2 syndrome is frequent, occurring in different degrees. Echocardiography is a valuable tool in detecting RV myocardial abnormalities in this condition. The use of 2D RV4LS, RVFWLS, and 3DEF offers reliable indicators of RV systolic dysfunction in this rare, challenging cardiomyopathy.

FUNDAMENTO: A síndrome do PRKAG2 é uma doença hereditária autossômica dominante rara, de início precoce. Objetivamos descrever os achados ecocardiográficos do ventrículo direito (VD) usando modalidades bi e tridimensionais (2D e 3D), incluindo índices de deformação miocárdica nesta cardiomiopatia. Também objetivamos demonstrar se esta técnica poderia identificar alterações na função do VD que pudessem distinguir quaisquer achados particulares. MÉTODOS: Trinta pacientes com síndrome do PRKAG2 (R302Q e H401Q) geneticamente comprovada, 16 (53,3%) do sexo masculino, com idade média de 39,1 ± 15,4 anos, foram submetidos a exame ecocardiográfico completo. A visão de 4 câmaras com foco no VD foi adquirida para medições 2D e 3D. Os testes t de Student ou Wilcoxon-Mann-Whitney foram usados para comparar as variáveis numéricas entre 2 grupos, e p < 0,05 foi considerado significativo. RESULTADOS: Doze pacientes (40%) tiveram marca-passo implantado por 12,4 ± 9,9 anos. A espessura diastólica média da parede livre do VD foi de 7,9 ± 2,9 mm. O strain longitudinal de 4 câmaras do VD (SL4VD), incluindo a parede livre e o septo interventricular, foi de -17,3% ± 6,7%, e o strain longitudinal da parede livre do VD (SLPLVD) foi de −19,1% ± 8,5%. A razão apical do SLPLVD mediu 0,63 ± 0,15. A fração de ejeção (FE) 3D média do VD foi de 42,6% ± 10,9% e abaixo dos limites normais em 56,7% dos pacientes. Correlação positiva ocorreu entre FE 3D do VD, SL4VD e SLPLVD, principalmente para pacientes sem marca-passo (p = 0,006). CONCLUSÃO: O envolvimento do VD em PRKAG2 é frequente e ocorre em diferentes graus. A ecocardiografia é uma ferramenta valiosa na detecção de anormalidades miocárdicas do VD nesta condição. O uso de SL4VD 2D, SLPLVD e FE 3D oferecem indicadores confiáveis de disfunção sistólica do VD nesta cardiomiopatia rara e desafiadora.

Mahaim Revisited.

The name Ivan Mahaim is well-known to electrophysiologists. However, alternative anatomical substrates can produce the abnormal rhythms initially interpreted on the basis of the pathways he first described. These facts have prompted suggestions that Mahaim should be deprived of his eponym. It is agreed that specificity is required when describing the pathways that produce the disordered cardiac conduction, and that the identified pathways should now be described in an attitudinally appropriate fashion. The authors remain to be convinced that understanding will be enhanced simply by discarding the term 'Mahaim physiology' from the lexicon. It is fascinating to look back at the history of accessory atrioventricular junctional conduction pathways outside the normal accessory atrioventricular conduction system, and their possible role in rhythm disturbances. It took both the anatomist and the clinical arrhythmologist quite some time to understand the complex anatomical architecture and the ensuing electrophysiological properties. Over the years, the name Mahaim was often mentioned in those discussions, although these pathways were not the ones that produced the eponym. The reason for this review, therefore, is to present relevant information about the person and what followed thereafter.

Miniseries 2-Septal and paraseptal accessory pathways-Part I: The anatomic basis for the understanding of para-Hisian accessory atrioventricular pathways.

AIMS: Although the anatomy of the atrioventricular conduction axis was well described over a century ago, the precise arrangement in the regions surrounding its transition from the atrioventricular node to the so-called bundle of His remain uncertain. We aimed to clarify these relationships. METHODS AND RESULTS: We have used our various datasets to examine the development and anatomical arrangement of the atrioventricular conduction axis, paying particular attention to the regions surrounding the point of penetration of the bundle of His. It is the areas directly adjacent to the transition of the atrioventricular conduction axis from the atrioventricular node to the non-branching atrioventricular bundle that constitute the para-Hisian areas. The atrioventricular conduction axis itself traverses the membranous part of the ventricular septum as it extends from the node to become the bundle, but the para-Hisian areas themselves are paraseptal. This is because they incorporate the fibrofatty tissues of the inferior pyramidal space and the superior atrioventricular groove. In this initial overarching review, we summarize the developmental and anatomical features of these areas along with the location and landmarks of the atrioventricular conduction axis. We emphasize the relationships between the inferior pyramidal space and the infero-septal recess of the subaortic outflow tract. The details are then explored in greater detail in the additional reviews provided within our miniseries. CONCLUSION: Our anatomical findings, described here, provide the basis for our concomitant clinical review of the so-called para-Hisian arrhythmias. The findings also provide the basis for understanding the other variants of ventricular pre-excitation.

Miniseries 2-Septal and paraseptal accessory pathways-Part II: Para-Hisian accessory pathways-so-called anteroseptal pathways revisited.

Surgeons, when dividing bypass tracts adjacent to the His bundle, considered them to be 'anteroseptal'. The area was subsequently recognized to be superior and paraseptal, although this description is not entirely accurate anatomically, and conveys little about the potential risk during catheter interventions. We now describe the area as being para-Hisian, and it harbours two types of accessory pathways. The first variant crosses the membranous septum to insert into the muscular ventricular septum without exiting the heart, and hence being truly septal. The second variant inserts distally in the paraseptal components of the supraventricular crest, and consequently is crestal. The site of ventricular insertion determines the electrocardiographic expression of pre-excitation during sinus rhythm, with the two types producing distinct patterns. In both instances, the QRS and the delta wave are positive in leads I, II, and aVF. In crestal pathways, however, the QRS is ≥ 140 ms, and exhibits an rS configuration in V1-2. The delta wave in V1-2 precedes by 20-50 ms the apparent onset of the QRS in I, II, III, and aVF. In the true septal pathways, the QRS complex occupies ∼120 ms, presenting a QS, W-shaped, morphology in V1-2. The delta wave has a simultaneous onset in all leads. Our proposed terminology facilitates the understanding of the electrocardiographic manifestations of both types of para-Hisian pathways during pre-excitation and orthodromic tachycardia, and informs on the level of risk during catheter ablation.

Anatomy of the conduction tissues 100 years on: what have we learned?

Knowledge of the anatomy of the 'conduction tissues' of the heart is a 20th century phenomenon. Although controversies still continue on the topic, most could have been avoided had greater attention been paid to the original descriptions. All cardiomyocytes, of course, have the capacity to conduct the cardiac impulse. The tissues specifically described as 'conducting' first generate the cardiac impulse, and then deliver it in such a fashion that the ventricles contract in orderly fashion. The tissues cannot readily be distinguished by gross inspection. Robust definitions for their recognition had been provided by the end of the first decade of the 20th century. These definitions retain their currency. The sinus node lies as a cigar-shaped structure subepicardially within the terminal groove. There is evidence that it is associated with a paranodal area that may have functional significance. Suggestions of dual nodes, however, are without histological confirmation. The atrioventricular node is located within the triangle of Koch, with significant inferior extensions occupying the atrial vestibules and with septal connections. The conduction axis penetrates the insulating plane of the atrioventricular junctions to continue as the ventricular pathways. Remnants of a ring of cardiomyocytes observed during development are also to be found within the atrial vestibules, particularly a prominent retroaortic remnant, although that their role has still to be determined. Application of the initial criteria for nodes and tracts shows that there are no special 'conducting tissues' in the pulmonary venous sleeves that might underscore the abnormal rhythm of atrial fibrillation.

QRS alternans during right ventricular pacing while ablating a concealed left sided accessory pathway.

A 16-year-old boy was referred for an electrophysiological study for documented regular narrow complex tachycardia. A diagnosis of a concealed left lateral accessory pathway was made with an eccentric atrial activation sequence both during tachycardia and right ventricular (RV) pacing. The pathway was mapped at the left posterior mitral vestibule during RV pacing, performed through the distal tip of the His bundle catheter pushed into right ventricular outflow tract. An unusual response to ventricular stimulation with alternation of QRS complex width and morphology was noted. The possible mechanisms are hereby discussed.

Critical Assessment of the Concepts and Misconceptions of the Cardiac Conduction System over the Last 100 Years: The Personal Quest of Robert H. Anderson.

Anatomical concepts regarding the conduction system of the heart have been a matter of debate since pioneering work done at the beginning of the 20th century. Robert H. Anderson was actively involved in this field for half a century. We aimed to investigate how his own concepts evolved over time. We have assessed anatomical concepts relating to the cardiac conduction system appearing since the key contributions made in the initial decade of the 20th century, analyzing them from the perspective of Robert H. Anderson, particularly focusing on the anatomical aspects of structures such as accessory atrioventricular pathways, including the so-called Mahaim-type fibers, connections between the atrioventricular node and the atrial myocardium, and so-called "specialized" internodal atrial tracts. To accomplish this task, we have taken as our starting point the initial concepts published in the first decade of the century, along with those subsequently reported up to 1976, and assessing them in the light of our most recently published works. The concepts put forward by Robert Anderson with regard to atrioventricular nodal bypass tracts, atrioventricular nodal inputs, decrementally conducting accessory pathways, and "tracts" for internodal atrial conduction, have remained consistent along the time frame of half a century.