Congenital heart disease (CHD) is one of the main supportive diseases of extracorporeal membrane oxygenation in children. The management of extracorporeal membrane oxygenation (ECMO) for pediatric CHD faces more severe challenges due to the complex anatomical structure of the heart, special pathophysiology, perioperative complications and various concomitant malformations. The survival rate of ECMO for CHD was significantly lower than other classifications of diseases according to the Extracorporeal Life Support Organization database. This expert consensus aims to improve the survival rate and reduce the morbidity of this patient population by standardizing the clinical strategy.The editing group of this consensus gathered 11 well-known experts in pediatric cardiac surgery and ECMO field in China to develop clinical recommendations formulated on the basis of existing evidences and expert opinions.The primary concern of ECMO management in the perioperative period of CHD are patient selection, cannulation strategy, pump flow/ventilator parameters/vasoactive drug dosage setting, anticoagulation management, residual lesion screening, fluid and wound management and weaning or transition strategy. Prevention and treatment of complications of bleeding, thromboembolism and brain injury are emphatically discussed here. Special conditions of ECMO management related to the cardiovascular anatomy, haemodynamics and the surgical procedures of common complex CHD should be considered.The consensus could provide a reference for patient selection, management and risk identification of perioperative ECMO in children with CHD.Video abstract (MP4 104726 kb)The online version contains supplementary material available at 10.1007/s12519-022-00636-z. Since the 1980s, the number of cardiac ECMO cases has increased dramatically, though neonatal respiratory failure remains to be the most common indication for ECMO support [. The most common neonatal diagnosis requiring respiratory ECLS  was congenital diaphragmatic hernia (32%), followed by meconium aspiration syndrome (24%) and persistent pulmonary hypertension (21%) [Until the 1970s, extracorporeal membrane oxygenation (ECMO) was reported to be successfully used in a neonate with acute respiratory failure [ support . ECMO isc hernia 2%, folloc hernia 2%, folloVeno-arterial ECMO (VA ECMO) is the main support mode for CHD. According to the data from Extracorporeal Life Support Organization (ELSO) registry, a total of 19,629 cases with CHD from 350 international centers worldwide from 1990 to 2019 have been supported by ECMO . Among t. In 2021, ECMO was used for respiratory support in 126 children and for circulatory support in 422 children with a survival rate of 59.5% [In China, ECMO was reported to be successfully used in a neonate with CHD in 2008 . A totalof 59.5% . A totalof 59.5% .ECMO support after arterial switch operations (ASOs) accounted for 21.2% of total ECMO cases with CHD . ChildreMost neonatal cardiac ECMO occurs during the perioperative period and particularly the post-procedure period . Periope2/minute; (2) persistent tissue hypoperfusion: blood pH < 7.15, BE < -5 mmol/L, lactate > 7.3 mmol/L, urine output < 1 mL/kg/hour, capillary refill time > 3 seconds, central venous oxygen saturation (SVO2) < 60% or arteriovenous oxygen saturation difference (AVO2) > 30% for cyanotic CHDs; (3) persistent hypotension: the blood pressure is two standard deviations lower than that of normal blood pressure at the same age, such as for systolic blood pressure < 50 mmHg (neonates), < 60 mmHg (infants) and  < 70 mmHg (children); (4) patients presenting with low blood pressure under two or more high-dose inotropes and/or vasopressors, such as epinephrine > 0.3 µg/kg/minute, dopamine > 10 µg/kg/minute, etc., or vasoactive–inotropic score is over 20 for two or more times and keeps increasing; (5) severe respiratory failure: severe hypoxia or respiratory acidosis persists even after conventional aggressive treatment, such as pH < 7.1, partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) < 60–80 mmHg or oxygenation index > 40, lasting 3–6 hours; (6) malignant arrhythmias: ECMO should be considered when severe arrhythmias, such as ventricular fibrillation, cardiac arrest or pulseless electrical activity and short bursts of ventricular tachycardia occur repeatedly and cannot be terminated by antiarrhythmic drugs, inotropes or temporary cardiac pacemakers. Consideration for early initiation of ECMO is important as delayed initiation (beyond 6 hours of cardiogenic shock state) is associated with worse outcomes.ECMO should be initiated as early as possible if with the following indications –16: (1) ECMO should not be used under the following conditions : (1) proVA ECMO was the most commonly used mode for most congenital heart diseases perioperatively. Cannulation site and strategy were determined by the patient’s body size, underlying cardiac anatomy and different surgical procedures for CHD. The commonly used cannulation strategy is listed in Table Peripheral vessel cannulation requires usually open surgical access . The tipVO2) should be continuously monitored. The cardiac index should be maintained at 2.5–3 L/minute/m2 and the ratio of oxygen delivery (DO2) to oxygen consumption (VO2) should be set at least > 3:1 by adjusting pump flow and hemoglobin level [During ECMO, mixed venous oxygen saturation  or  ≥ 50–100 × 10 9/L (nonbleeding patient), fibrinogen > 1.5 g/L  or  > 1 g/L (nonbleeding patient). If a maximum dose of UFH cannot achieve the targeted ACT value, fresh frozen plasma could be infused to maintain antithrombin activity at > 50%–80% or 0.5–0.8 U/mL [A bolus dose of UFH ranging from 50 to100 units/kg is given after the exposure of the vessels and before insertion of the cannulas for ECMO. Patients with severe coagulopathy, or active bleeding can receive a UFH bolus at the lower end of this range. Nevertheless, in the immediate postoperative transferring from CPB, bolus dosing of UFH may not be necessary . UFH can0.8 U/mL .Direct thrombin inhibitors (DTIs) have been used in both adult and pediatric patients with heparin-induced thrombocytopenia (HIT), heparin resistance and non-HIT thrombocytopenia , 30. TheWhen severe left ventricle (LV) dysfunction is supported with VA ECMO, continuous flow increases the pressure of the aortic root and LV afterload , 32. PooAfter cardiac tamponade was excluded, the implications of poor LV decompression were reduced arterial pulse pressure (< 10 mmHg), increased pulmonary capillary wedge pressure (PCWP) or left atrium (LA) pressure (> 20 mmHg), pulmonary edema, closed aortic valve, increased LA or LV end-diastolic diameter and aggravated mitral valve regurgitation .Conservative decompression was the first-line strategy: (1) titrate the ECMO flow  and use Postoperative residual lesions of CHD can significantly increase the risk of postoperative complications and mortality rate . Therefo2, etc. Children with a single ventricle may have insidious manifestations and may not present a significant increase in the left atrial or central venous pressure until the auxiliary flow is reduced to 30%–40%.Common residual lesions include residual ventricular septal defects, stenosis and dysplasia of the pulmonary artery branch, stenosis of the left and right ventricular outflow tracts, pulmonary vein stenosis, B-T/Sano duct stenosis or too great, severe valvular regurgitation, bulky pulmonary collateral and coronary artery disease , 42. In The first option for examination to identify residual anatomical malformation is ultrasound , 42. WheChildren with VA ECMO during the perioperative period of CHD need appropriate fluid to maintain cardiac output and ECMO flow. Dynamic monitoring of central venous pressure (CVP), PCWP, pre-pump pressure of circuit and other comprehensive evaluations of volume status are crucial. During the early period of ECMO support, bleeding, insensible fluid loss or capillary leakage syndrome may be attributed to insufficient ECMO flow. When the pre-pump pressure of ECMO becomes more negative (below -40 to -30 mmHg), the venous line vibrates or the inferior vena cava collapses  and collAbout 49%–59% of children on ECMO with CHD developing acute kidney injury (AKI) and fluid overload require renal replacement therapy (RRT) , 49. LowTo avoid serious air embolism, we recommend the input and output interfaces of CRRT be connected to the post-pump part of the ECMO circuit Fig. . ParalleThe safety and effect of peritoneal dialysis during ECMO in children with CHD should be affirmed –63. BecaCentral cannulation generally requires delayed sternal closure. The sternal skin should be sutured as much as possible or covered with sterile dressings . Strict When cardiac function recovers after 5–7 days of ECMO support, weaning can be considered. If there is no sign of improvement in cardiac function for longer than two weeks, transition to an intermediate- or long-term mechanical cardiac support device or heart transplant should be considered . If irre2O, PEEP 5–15 cmH2O and PaO2/FiO2 > 200 mmHg after biventricular correction, PCO2 ≤ 45 mmHg, pH > 7.3, SvO2 ≥ 65%, blood lactate, electrolyte and hematocrit (HCT) values within the normal range; (4) in patients with a single ventricle, it is necessary to adjust the balance of systemic/pulmonary blood flow according to the cardiac surgical procedures and the level of peripheral blood oxygen saturation (SpO2). The oxygenation index and mechanical ventilation parameters should meet the targets and all conditions remain stable.When the pump flow is gradually reduced to less than 30% of the full flow for 6–24 hours, weaning can be attempted if the following conditions are met , 68–70: First-aid medicines, equipment and blood availability should be accessible to address the possible risks during weaning. The trial off VA ECMO for CHD is similar to the ELSO guideline , 71, 72.Bleeding after cardiac surgery could be caused by surgical factors or coagulation disorder. The optimal treatment depends on the cause, amount and site of bleeding. For surgical bleeding, operative hemostasis should be performed. For light bleeding other than the brain, the anticoagulation level can be adjusted downward. In cases of intracranial hemorrhage and/or massive bleeding, anticoagulants should be suspended until the bleeding is controlled. Hemostatic and blood products should be given as needed. For refractory bleeding, anti-fibrinolytic therapy  should be initiated if necessary.ECMO-associated thrombosis could occur both in the ECMO circuit and vessels. Coagulation disorders after prolonged CPB, high-dose vasopressor infusion, delayed initiation of heparin and excessive infusion of coagulation substrate increase the risk of thrombosis. An individual anticoagulation strategy, careful surgical hemostasis, stable internal environment, reasonable infusion of coagulation substrate, appropriate vasopressor usage, effective left heart decompression  and redu2 levels to avoid the effects of hyperventilation on cerebral vessels. In patients with mild intracranial hemorrhage, close monitoring of neurological function and optimization anticoagulant strategy are required. ECMO discontinuation should be considered in cases of severe intracranial hemorrhage with an expected poor prognosis.The risk factors for ECMO-related brain injury include younger age , lower body weight (< 3 kg), exposure to CPR, acidosis, surgical factors, thromboembolism, systemic anticoagulation and cerebral hypoperfusion . RoutineECPR is the rapid deployment of VA ECMO to provide reperfusion with oxygenation and cardiac support when conventional cardiopulmonary resuscitation (CPR) fails to restore sustained spontaneous circulation . Owing tAccording to the anatomical characteristics of CHD and the speed of rescue, the ECPR cannulation strategy is formulated, central cannulation can be performed in the early stage within the postoperative 14 days, and cervical or femoral arteriovenous cannulation can be performed in children before surgery or during the late postoperative period , 82.One of the key factors for the success of ECPR is the full effectiveness of CRP and the rapid implementation of ECMO , 84. AftECMO management differences after Norwood surgery for HLHS is related to the procedures of Sano or B-T shunt. After Sano shunt, pulmonary vessels only receive blood supply in ventricular systolic stage, whereas after B-T shunt, pulmonary vessels receive continuous blood supply in the systolic and diastolic stages, and the latter is prone to resulting in a greater risk of coronary insufficiency. To provide sufficient systemic and coronary perfusion during ECMO running, in addition to strengthening cardiac function and maintaining higher HCT level, excessive reduction in pulmonary vascular resistance should be avoided by adjustment of medicine and ventilator setting.For uncorrected or stage 1 single ventricle, when patent ductus arteriosus (PDA) (or B-T shunt) closure and/or restricted atrial septal defect (ASD) occurs, insufficient pulmonary and systemic blood mixing leads to severe hypoxemia, elevated pulmonary arterial and venous pressure and finally to circulatory failure. Under these conditions, ECMO support should be considered. A high ECMO flow rate (150–200 mL/kg/minute) is usually required to compensate for the flow shunt into the pulmonary circulation . Emergen2 blood levels perhaps might lead to insufficient cerebral blood flow, further resulting in insufficient venous drainage [Bidirectional Glenn and Fontan circulations rely on passive low pulmonary resistance. When central cannulation is adopted after early surgery, superior vena cava cannulation should be established first to achieve venous drainage and reduced intracranial pressure to decrease intracranial bleeding risks. If venous drainage is insufficient, inferior vena cava cannulation should be added. Excessive ventilation causing low COdrainage , 17.When higher pump flow is provided, maintaining pulsatile blood flow by a certain degree of ventricle filling and output is needed to avoid blood stasis in Fontan graft . In patiVarious causes of bidirectional Glenn and Fontan circulation failure should be investigated, such as arrhythmia, anatomic obstruction to flow, pulmonary vascular remodeling, atrioventricular valve dysfunction, univentricular diastolic dysfunction and chronic under filling and/or univentricular systolic dysfunction. As one might imagine, the outcome of extracorporeal support largely depends upon the underlying physiology and mechanism for “Fontan failure” .ECMO is effective for early postoperative support of Fontan circulation failure. However, patients with late-phase failure usually present with extreme end-organ failure, such as protein losing enteropathy, plastic bronchitis, cirrhosis, or renal failure. The middle-to-late phase failure patients are appropriate transplant candidates and are better suited for transitioning to more durable mechanical support (ventricular-assist device) via ECMO .Pulmonary hypertension is uncommon in patients with TGA/IVS). The incidence of TGA/IVS with pulmonary hypertension was 1%–12% , 89. IncVA ECMO blood flow may aggravate aortic regurgitation and increase the risk of left ventricular afterload and left ventricular dramatic expansion, so aortic regurgitation should be assessed carefully before ECMO implantation. If it is found after ECMO implantation, early left ventricular decompression or surgical correction is required .Careful attention to the anatomy of the head and neck vessels  is required before ECMO cannulation to ensure brain perfusion with oxygenated ECMO flow .Due to secondary severe myocardial ischemia, most of the ALCAPA patients had severe cardiac insufficiency, with high incidence of perioperative adverse events , 92. Pla2 and VO2 and to promote the recovery of cardiac function and organ protection. The anticoagulation strategy should be tailored by considering the unique bleeding and clotting risks. Left ventricular decompression and pericardial tamponade should be monitored carefully in the early stage of ECMO. Residual lesions, volume overload, bleeding and brain complication should be identified and intervened as soon as possible. Special considerations for complicated CHD should be considered during ECMO management.This consensus provided a comprehensive clinical and technical approach for ECMO support in CHD in children. Indications and contraindications should be evaluated carefully before ECMO application. The cannulation strategy is determined based on the patient’s body size, cardiac anatomy and different surgical procedures of CHD. ECMO pump flow, ventilator parameters and vasoactive drugs should be adjusted according to different ECMO support stages and goals as well as special characteristics of cardiac function, procedures and hemodynamics, to maintain the balance of DO


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. Trinta pacientes com síndrome do PRKAG2 (R302Q e H401Q) geneticamente comprovada, 16  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.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 . 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  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. A literatura também descreve 28 mutações adicionais.3 A mutação PRKAG2 resulta na perda da função da subunidade γ2 da AMPK e apresenta um defeito metabólico responsável pela glicogenose. O principal fenótipo consiste em hipertrofia ventricular associada a anormalidades no sistema de condução cardíaca, incluindo síndrome de pré-excitação ventricular.4O gene PRKAG2 foi inicialmente descrito em 2000 como parte ativa do metabolismo no processo de transcrição da proteína quinase ativada por AMP (AMPK).6A mutação PRKAG2 é considerada uma doença rara, embora esteja provavelmente subestimada, pois muitos casos são diagnosticados inadequadamente, sendo muitas vezes classificados como cardiomiopatia hipertrófica familiar. O padrão de herança é dominante, com penetrância completa e graus variados de expressão e prevalência ainda não mencionados na literatura.strain / strain rate ) por speckle tracking (STE) são técnicas relativamente recentes, porém já utilizadas para a avaliação da função do ventrículo esquerdo (VE). Mais recentemente, essas técnicas também foram validadas para avaliação da função do ventrículo direito (VD).8A ecocardiografia bi e tridimensional (2D e 3D) e os índices de deformação miocárdica , detectados por meio de teste genético de sequenciamento Sanger. Todos os pacientes foram submetidos a exame clínico, com eletrocardiograma convencional de 12 derivações e ecocardiograma. O conselho de revisão institucional aprovou o protocolo e todos os pacientes assinaram um termo de consentimento informado. Nosso estudo foi realizado seguindo as diretrizes das Boas Práticas Clínicas e foi aprovado pelos comitês de ética locais.15 Todos os estudos foram realizados utilizando um sistema ecocardiográfico disponível comercialmente, máquina Vivid E9 . O exame incluiu o modo M, medidas 2D, STE 2D de strain longitudinal e medidas 3D de acordo com as Diretrizes para a Avaliação Ecocardiográfica do Coração Direito em Adultos: um relatório da ASE.16 A visão de 4 câmaras com foco no VD foi adquirida para medidas 2D e 3D, tendo-se o cuidado para obter a imagem que demonstrasse o diâmetro máximo. Foram medidas as dimensões lineares 2D do VD, incluindo as dimensões basais, médias e longitudinais do VD. A via de saída do VD foi medida no final da diástole no corte paraesternal eixo longo. A espessura da parede do VD foi medida na diástole, a partir do corte subcostal, utilizando-se o modo M.Todos os pacientes foram submetidos a exame ecocardiográfico transtorácico completo, seguindo as recomendações da Sociedade Americana de Ecocardiografia (ASE) e da Associação Europeia de Imagem Cardiovascular (EACVI).A excursão sistólica do plano anular tricúspide (TAPSE) foi obtida pelo modo M, medida a partir do anel lateral tricúspide.strain longitudinal de 4 câmaras do VD (SL4VD) foi calculado pela média dos valores de todos os 6 segmentos do VD. O strain longitudinal da parede livre do VD (SLPLVD) foi obtida pela média dos 3 segmentos da parede livre do VD: basal, médio e apical. Também calculamos a razão apical da parede livre do VD usando a equação: [strain longitudinal de pico sistólico (SLPS) apical / ]. Todos os dados foram revisados offline. O ecocardiograma transtorácico 3D do VD foi realizado em todos os pacientes. Seis batimentos consecutivos controlados por eletrocardiograma foram adquiridos para gerar o volume completo do VD. O pós-processamento das imagens 3D em tempo real foi realizado no software TomTec 1.1, com o traçado endocárdico de todos os planos. Os volumes do VD foram calculados de forma semiautomática ao longo de todo o ciclo cardíaco, a partir dos quais foram obtidos o volume diastólico final e o volume sistólico final e calculados o volume sistólico e a fração de ejeção (FE). A reprodutibilidade intra e interobservador foi avaliada em uma subamostra de 9 pacientes selecionados aleatoriamente.A veia cava inferior foi medida proximal à junção das veias hepáticas no final da expiração. O O tamanho amostral utilizado foi de conveniência devido à raridade dessa condição. As variáveis categóricas foram apresentadas por frequências absolutas e relativas e as variáveis numéricas como média ± desvio padrão se distribuídas normalmente e mediana ± intervalo interquartil se distribuídas anormalmente. A normalidade das variáveis numéricas foi avaliada pelo teste de Shapiro-Wilk. Os testes t de Student ou Wilcoxon-Mann-Whitney foram usados para comparar variáveis numéricas entre 2 grupos usados para amostras independentes. A associação entre as variáveis categóricas foi avaliada pelo teste exato de Fisher. O coeficiente de correlação de Spearman foi utilizado para avaliar a associação entre 2 variáveis numéricas.Os 30 casos foram atribuídos aleatoriamente números de 1 a 30 usando o software R. Para avaliar a consistência e reprodutibilidade, 2 observadores independentes selecionaram aleatoriamente 9 números para remensuração. A escolha do número de casos foi arbitrária.As diferenças médias e coeficientes de correlação intraclasse (CCI) foram obtidos. Seus intervalos de confiança (IC) intra e interobservador foram ambos de 95%. As medidas intra e interobservador foram avaliadas pelo teste de Shapiro-Wilk. Testes t de Student para amostras pareadas foram usados para comparar as diferenças médias.As análises foram realizadas no software R versão 3.5.2, e p < 0,05 foi considerado significativo.flutter foram os sinais prevalentes.A Os parâmetros ecocardiográficos do VD estão listados na É importante relatar que, durante o ecocardiograma, apenas 1 paciente apresentou fibrilação atrial. Medida pelo corte subcostal em modo M, a espessura diastólica mediana da parede lateral do VD foi de 7,0 ± 3,0 mm   . ApenasA porção anterior do eixo longo paraesternal da dimensão da via de saída do VD no nível proximal apresentou valores superiores ao normal em 23% dos pacientes, conforme relatado na literatura, exceto para a dimensão longitudinal. Esse valor sugere que o aumento da câmara do VD ocorreu na seção transversal.A regurgitação tricúspide foi detectada em metade dos pacientes, mas apenas 4 apresentaram pressão sistólica da artéria pulmonar acima dos limites normais, e o valor máximo estimado atingiu 48 mmHg.A veia cava inferior estava dilatada em apenas 2 pacientes.Em 3 pacientes, o SL4VD estava significativamente reduzido, relacionado à parede lateral mais espessada   .A A FE do VD estava dentro dos limites normais em 13 pacientes e abaixo de 35% em 7 pacientes   .Os pacientes com marca-passo eram significativamente mais velhos , e apresentavam maior proporção de fibrilação atrial em comparação aos pacientes sem marca-passo . O marca-passo foi implantado aos 38,1 ± 13 anos, e o tempo mediano de uso foi de 12,4 ± 9,9 anos.Os pacientes com marca-passo apresentaram valores significativamente menores de FEVE 3D, encurtamento fracionado e strain circunferencial global 3D.Verificamos uma diferença estatisticamente significativa entre as medidas do segmento basal e médio da SLPLVD entre os pacientes com e sem marca-passo, conforme mostrado na No entanto, não apareceram outras diferenças significativas entre os achados ecocardiográficos do VD entre os pacientes com e sem marca-passo.strain e FE do VD foram avaliadas, conforme apresentado na As correlações entre as variáveis de Também verificamos uma correlação positiva entre a redução da FEVE e SLPLVD  .strain e das medidas de 3D, bem como a CCI e o IC para variabilidade inter e intraobservador estão resumidos na A reprodutibilidade do 17 A síndrome do PRKAG2 possui diferentes fenótipos cardíacos, que variam desde uma condição assintomática até a morte súbita cardíaca, incluindo hipertrofia biventricular, pré-excitação, anormalidades na condução atrioventricular, flutter atrial e fibrilação.19Mutações no gene PRKAG2 alteram a homeostase da AMPK, e a avaliação ecocardiográfica de pacientes com a mutação é uma oportunidade para avaliar as potenciais consequências sistêmicas a longo prazo da ativação da AMPK. Ao avaliar essas consequências, novas linhas de pesquisa podem indicar vias metabólicas envolvidas na fisiopatologia da doença levando ao reconhecimento parcial ou total do fenótipo.20 Este estudo mostrou que pacientes com variantes genéticas de PRKAG2 apresentam prognóstico desfavorável, com alta taxa de complicações, incluindo início juvenil de doença de condução, IC avançada e arritmias potencialmente letais.Uma grande coorte multicêntrica da Europa foi publicada recentemente relatando dados de 90 pacientes com variantes de PRKAG2.21 Até onde sabemos, esta pesquisa representa o maior estudo ecocardiográfico do VD em uma população com mutação PRKAG2. Visamos descrever os achados do VD nessa rara doença genética e a ocorrência, incidência e grau de disfunção.A avaliação do tamanho do VD e do desempenho sistólico é cada vez mais solicitada devido ao seu significado reconhecível e prognóstico, especialmente na cardiomiopatia hipertrófica, cardiomiopatia arritmogênica do VD e amiloidose.23 Rosca et al.,23 relataram que pacientes com cardiomiopatia hipertrófica apresentaram aumento da espessura da parede do VD em comparação com controles, com aumento do risco calculado de morte súbita cardíaca.23O VD foi acometido na grande maioria dos pacientes. A hipertrofia do VD ocorreu em 90% dos pacientes, apresentou padrão regular, envolveu todas as porções da câmara e atingiu 20 mm em 1 caso. Esse achado é semelhante a outras doenças infiltrativas ou genéticas.strain do VD não apresentaram padrão de apical sparing , conforme descrito na amiloidose cardíaca sistêmica de cadeia leve.24 Vale ressaltar que o SLPLVD foi viável em todos os pacientes.Avaliamos a deformação miocárdica (SL4VD e SLPLVD), volumes do VD e FE desses pacientes. Verificamos que o SLPLVD dos segmentos basais apresentou valores inferiores aos dos segmentos médio e apical. Entretanto, a razão da parede livre do VD mostrou que as análises de 8 Alguns pacientes  também apresentavam FEVE reduzida, principalmente aqueles com marca-passo. Conforme relatado anteriormente, pacientes com marca-passo apresentaram valores significativamente mais baixos de FEVE 3D, encurtamento fracionado e strain circunferencial global 3D.25Verificamos que a FE do VD estava abaixo dos limites normais em mais da metade dos pacientes  e, em 7 pacientes, a FE do VD estava abaixo de 35%. Esses valores não foram afetados pelo marca-passo, podendo indicar um sinal diferencial desta doença quando comparado a outros fenótipos hipertróficos. Consideramos FE do VD ≥ 45% como normal.Uma redução da FE do VD ocorreu em uma proporção maior de pacientes e provavelmente será um sinal diferencial em comparação com outras cardiomiopatias hipertróficas, como as doenças de Fabry e Danon.15A ecocardiografia é uma técnica prática e não invasiva para identificar alterações morfológicas e funcionais na prática clínica.27Mesmo pacientes assintomáticos apresentaram SL4VD e SLPLVD abaixo dos limites normais de referência. Como a viabilidade da estimativa 3D do volume do VD tem sido comprovada nessa síndrome, esse método pode ser aplicado de forma confiável em diagnósticos clínicos.28A ecocardiografia não apresenta efeitos nocivos em pacientes com marca-passo e tem menor custo, maior portabilidade e maior facilidade de reaplicação do que a ressonância magnética cardíaca.27 É interessante notar que, com o uso do Doppler, não detectamos obstrução na via de saída do VD em repouso. Um relato de caso recentemente publicado detectou uma obstrução dinâmica da via de saída biventricular em um paciente com episódio de síncope. Testes genéticos revelaram que o paciente era heterozigoto para mutação missense R302Q no gene PRKAG2, como na maioria dos nossos casos.26Observamos que os índices ecocardiográficos convencionais, como TAPSE, não eram indicadores confiáveis para detecção de disfunção do VD. Em estudos anteriores, com outras doenças infiltrativas, esses indicadores mostraram menor sensibilidade para detectar alterações miocárdicas funcionais do que as análises de STE 2D do VD.Confirmamos uma correlação positiva entre o SLPLVD e a FE do VD, com significância estatística. Esses achados indicam que os índices de deformação são um método rápido e amplamente disponível para detectar disfunção, comparável à FE 3D em pacientes com a mutação PRKAG2. Além disso, ocorreu uma correlação positiva, associando reduções tanto da FEVE quanto da SLPLVD.Reconhecemos limitações no estudo, como um número relativamente pequeno de pacientes. O software para obtenção de SL4VD e SLPLVD foi adaptado do software desenvolvido para medir o VE. A regurgitação tricúspide foi detectada em metade da população estudada e o aumento da pressão pulmonar sistólica ocorreu em 4 pacientes, que foi avaliada exclusivamente por esse método.São recomendadas pesquisas adicionais usando esses critérios prospectivamente e o uso de diferentes técnicas de imagem para comparação para validar ainda mais nossos achados.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 na cardiomiopatia PRKAG2. SL4VD 2D, SLPLVD e FE 3D são indicadores confiáveis de disfunção sistólica do VD nesta doença rara. Estudos longitudinais adicionais são necessários para melhor entender a história natural do envolvimento do VD e determinar seu impacto nos desfechos dos pacientes. 2 In nearly half of the reported cases, genomic changes involving this gene are due to the Arg302Gln mutation, which replaces arginine with glutamine at codon 302, known as R302Q. The literature also describes 28 additional mutations.3 The PRKAG2 mutation results in loss of function of the γ2 subunit of AMPK and features a metabolic defect responsible for glycogen metabolic disease. The main phenotype consists of ventricular hypertrophy associated with abnormalities in the cardiac conduction system, including ventricular pre-excitation syndrome.4The PRKAG2 gene was initially described in 2000 as an active part of metabolism in the transcription process of AMP-activated protein kinase AMPK).6PRKAG2 mutation is considered a rare disease, although it is probably underestimated, because many cases are improperly diagnosed, often being labeled as familial sarcomeric hypertrophic cardiomyopathy. The inheritance pattern is dominant, with complete penetrance and varying degrees of expression and prevalence still unmentioned in the literature.8Two- and three-dimensional (2D and 3D) echocardiography and myocardial deformation indices (strain/strain rate) by speckle tracking (STE) are relatively recent techniques, yet they are already used for assessing left ventricle (LV) function. More recently, these techniques have also been validated for assessing right ventricle (RV) function.9Our research group recently published a study of the LV echocardiography findings in this same series of patients.10 Compared to systemic circulation, pulmonary circulation has a much lower vascular resistance and greater pulmonary artery distensibility.14The recognized importance of the RV in cardiomyopathies is radically changing, and this significantly affects cardiac physiology, hemodynamics, and the development of symptoms.We aim to describe the RV echocardiographic findings using 2D and 3D echocardiography and STE. We also aim to identify if this technique could eventually detect any particular changes in RV function in glycogen storage cardiomyopathy when compared to LV. As little research exists associating RV echocardiographic findings with PRKAG2 syndrome, we seek to investigate the presence of echocardiographic parameters that could suggest RV hypertrophy associated with glycogen deposit cardiomyopathy.This is an observational, clinical, transversal study, based on a cohort of patients with genetically proven PRKAG2 syndrome. Patients with other hypertrophic cardiomyopathy etiologies were excluded. The target population consisted of 30 patients from 5 families with PRKAG2 gene mutation (28 Arg302Gln and 2 His401Gln), detected utilizing Sanger sequential genetic testing. All patients underwent clinical examination, with a standard 12-lead electrocardiogram and echocardiogram. The institutional review board approved the protocol and all patients signed a written informed consent form. Our study was performed following the guidelines of Good Clinical Practice and was approved by the local ethics committees.15 All studies were performed using a commercially available echocardiographic system, Vivid E9 machine . The examination included M-mode, 2D measurements, 2D STE of longitudinal strain, and 3D measurements according to The Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: a report from the ASE.16 The RV-focused, 4-chamber view was acquired for 2D and 3D measurements, and care was taken to obtain the image demonstrating the maximum diameter. RV 2D linear dimensions were measured, including RV basal, mid-cavity, and longitudinal dimensions. The RV outflow tract was measured at end-diastole in the parasternal long-axis view. RV wall thickness was measured in diastole, from the subcostal view, using M-mode imaging.All patients underwent a complete transthoracic echocardiography examination, following the recommendations of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI).Tricuspid annular plane systolic excursion (TAPSE) was obtained by M-mode, measured from the tricuspid lateral annulus.Inferior vena cava was measured proximal to the junction of the hepatic veins at end-expiration. RV 4-chamber longitudinal strain (RV4LS) was calculated by averaging values of all 6 RV segments. RV free wall longitudinal strain (RVFWLS) was obtained by averaging the 3 free wall RV segments: basal, mid, and apical. We also calculated the RVFW apical ratio using the equation: [apical peak systolic longitudinal strain (PSLS) / ]. All data were reviewed offline. RV transthoracic 3D echocardiography was performed in all patients. Six electrocardiogram-gated consecutive beats were acquired to generate the full RV volume. Post-processing of real-time 3D images was performed using TomTec software 1.1, with the endocardial tracing of all planes. RV volumes were semi-automatically computed throughout the entire cardiac cycle, from which end-diastolic volume and end-systolic volume were obtained, and stroke volume and ejection fraction (EF) were calculated. Intra- and interobserver reproducibility were assessed on a subsample of 9 randomly selected patients.The sample sized used was a convenience sample due to the rarity of this condition. Categorical variables were presented by absolute and relative frequencies and numerical variables as mean ± standard deviation if normally distributed and median ± interquartile range if abnormally distributed. The normality of the numerical variables was assessed using the Shapiro-Wilk test. Student’s t or Wilcoxon-Mann-Whitney tests were used to compare numerical variables between 2 groups used for independent samples. The association between categorical variables was assessed using Fisher’s exact test. Spearman’s correlation coefficient was used to assess the association between 2 numerical variables.The 30 cases were randomly assigned numbers from 1 to 30 using R software. To assess consistency and reproducibility, 2 independent observers randomly selected 9 numbers for remeasurement. The choice for the number of cases was arbitrary.Mean differences and intraclass correlation coefficients (ICC) were obtained. Their intra- and interobserver confidence intervals (CI) were both 95%. Intra- and interobserver measurements were assessed using the Shapiro-Wilk test. Student t-tests for paired samples were used to compare mean differences.The analyses were performed using R software version 3.5.2, and p < 0.05 was considered significant.RV echocardiographic parameters are listed in It is important to report that, during the echocardiogram, only 1 patient presented atrial fibrillation. Measured by the subcostal view using M-mode, RV lateral wall median diastolic thickness was 7.0 ± 3.0 mm   . Only 3Parasternal long-axis anterior portion of RV outflow tract dimension at the proximal level presented higher values compared to normal in 23% of patients, as reported in the literature, except for the longitudinal dimension. This value suggests that the RV chamber increase occurred in the transverse section.Tricuspid regurgitation was detected in half of patients, but only 4 presented pulmonary artery systolic pressure above normal limits, and the maximum estimated value reached 48 mmHg.Inferior vena cava was dilated in only 2 patients.In 3 patients, RV4LS was significantly reduced, relating to more thickened lateral wall   .RVEF was within normal limits in 13 patients and below 35% in 7 patients   .Patients with a pacemaker (PM) were significantly older (p < 0.001), and they had a higher proportion of atrial fibrillation compared to patients without PM (p = 0.018). The pacemaker was implanted at 38.1 ± 13 years, and the median time of use was 12.4 ± 9.9 years.Patients with PM presented significantly lower values of 3D LVEF, fractional shortening, and 3D global circumferential strain.We detected a statistically significant difference between measurements of RVFWLS basal and mid-segment between patients with and without PM, as shown in However, no other significant differences appeared among the RV echocardiographic findings between patients with and without PM.The correlations between the strain variables and RVEF were assessed, as shown in We also found a positive correlation between the reduction of LVEF and RVFWLS  .The reproducibility of strain and 3D measurements, and the ICC and CI for inter- and intraobserver variability are summarized in 17 PRKAG2 syndrome has different cardiac phenotypes, ranging from an asymptomatic condition to sudden cardiac death, including biventricular hypertrophy, pre-excitation, atrioventricular conduction abnormalities, atrial flutter, and fibrillation.19Mutations in the PRKAG2 gene alter AMPK homeostasis, and the echocardiographic assessment of patients with the mutation is an opportunity to assess the potential long-term systemic consequences of AMPK activation. By assessing these consequences, new lines of research could indicate metabolic pathways involved in the disease pathophysiology leading to partial or total phenotype recognition.20 This study showed that patients with PRKAG2 genetic variants have a poor prognosis with a high rate of complications, including juvenile onset of conduction disease, advanced HF, and potentially lethal arrhythmias.A large multicenter European cohort was recently published reporting data from 90 patients with PRKAG2 variants.21 To the best of our knowledge, this research represents the largest RV echocardiographic study in a population with PRKAG2 mutation. We aimed to describe the RV findings in this rare genetic disorder and the occurrence of dysfunction, incidence, and degree of dysfunction.Evaluation of RV size and systolic performance is increasingly in demand due to its recognizable significance and prognosis, especially in hypertrophic cardiomyopathy, arrhythmogenic RV cardiomyopathy, and amyloidosis.23 Rosca et al.23 related that patients with hypertrophic cardiomyopathy had increased RV wall thickness compared to controls with increased calculated sudden cardiac death risk.23The RV was affected in the great majority of patients. RV hypertrophy occurred in 90% of patients, presented a regular pattern, involved all portions of the chamber, and reached 20 mm in 1 case. This finding is similar to other infiltrative or genetic diseases.24 It is noteworthy that RVFWLS was feasible in all patients.We evaluated these patients’ myocardial deformation (RV4LS and RVFWLS), RV volumes, and EF. We found that the RVFWLS of basal segments showed lower values than mid and apical segments. However, the RVFW ratio showed that the RV strain analyses presented no apical sparing pattern, as described in systemic light-chain cardiac amyloidosis.8 Some patients (17.2%) also presented reduced LVEF, especially patients with PM. As previously reported, patients with PM presented significantly lower values of 3D LVEF, fractional shortening, and 3D global circumferential strain.25We found that RVEF was below normal limits in more than half of patients (56.7%), and, in 7 patients, RVEF was below 35%. These values were unaffected by PM, and they could indicate a differential signal of this disease when compared to other hypertrophic phenotypes. We considered normal RVEF ≥ 45%.RVEF reduction occurred in a greater proportion of patients and will likely be a differential signal compared to other hypertrophic cardiomyopathies such as Fabry and Danon diseases.15Echocardiography is a practical, non-invasive technique to identify morphological and functional alterations in clinical practice.27Even asymptomatic patients presented RV4LS and RVFWLS below normal reference limits. As the feasibility of 3D RV volume estimation has been proven in this syndrome, this method can be reliably applied in clinical diagnoses.28Echocardiography presents no harmful effects in patients with PM, and it has lower cost, higher portability, and easier reapplication than cardiac magnetic resonance.27 Interestingly, by using Doppler, we detected no obstruction in the RV outflow tract at rest. A recently published case report detected a dynamic biventricular outflow tract obstruction in a patient with a syncopal episode. Genetic testing revealed that the patient was heterozygous for R302Q missense mutation in the PRKAG2 gene, as in the majority of our cases.26We observed that conventional echocardiographic indices, like TAPSE, were unreliable indicators for RV dysfunction detection. In previous studies, with other infiltrative diseases, these indicators showed less sensitivity to detect functional myocardial alterations than RV 2D STE analyses.We confirmed a positive correlation between RVFWLS and RVEF, with statistical significance. These findings indicate that the deformation indices are a fast and widely available method to detect dysfunction, comparable to 3D EF in patients with the PRKAG2 mutation. Additionally, a positive correlation occurred, associating reductions of both LVEF and RVFWLS.We recognize limitations in the study, such as a relatively small number of patients. The software for obtaining RV4LS and RVFWLS was adapted from the software designed to measure the LV. Tricuspid regurgitation was detected in half of the study population, and increased systolic pulmonary pressure occurred in 4 patients, which was evaluated solely by this method.Additional research using these criteria prospectively and the use of different imaging techniques for comparison are recommended to further validate our findings.RV involvement in PRKAG2 is frequent and occurs in different degrees. Echocardiography is a valuable tool in detecting RV myocardial abnormalities in PRKAG2 cardiomyopathy. Two-dimensional RV4LS, RVFWLS, and 3D EF are reliable indicators of RV systolic dysfunction in this rare disease. Additional longitudinal studies are warranted to further understand the natural history of RV involvement and determine its impact on patient outcomes.


Echocardiography, CT and MRI have a crucial role in the management of congenital heart disease (CHD) patients. All of these modalities can be presented in a 2D or a 3D rendered format. The aim of this paper is to review the key advantages and potential limitations, as well as the future challenges of a 3D approach in each imaging modality. The focus of this review is on anatomic rather than functional assessment. Conventional 2D echocardiography presents limitations when imaging complex lesions, whereas 3D imaging depicts the anatomy in all dimensions. CT and MRI can visualise extracardiac vasculature and guide complex biventricular repair. Three-dimensional printed models can be used in depicting complex intracardiac relationships and defining the surgical strategy in specific lesions. Extended reality imaging retained dynamic cardiac motion holds great potential for planning surgical and catheter procedures. Overall, the use of 3D imaging has resulted in a better understanding of anatomy, with a direct impact on the surgical and catheter approach, particularly in more complex cases. Congenital heart disease patients require precise and reliable imaging to facilitate decision making with respect to surgery, catheter intervention or ongoing review. There is currently a plethora of imaging choices available, including echocardiography, CT and MRI. All of these modalities can be presented in a 3D rendered format or interrogated by “slicing” images in user-defined imaging planes. Guidelines have been published for each of these modalities for the congenital heart disease patient ,2,3,4. TThe use of a multiplanar approach permits detailed re-analysis of an imaging dataset in any desired plane, but does not present truly three-dimensional images. In contrast, 3D rendered images can be produced using ultrasound, CT and MRI data. However, the display of such images generally remains on a flat screen, with colour coding used to enhance depth perception. To overcome the limitations of this means of image display, 3D printing has gained traction to allow surgeons and interventionists to be able to have a static physical representation of the true cardiac anatomy. The aim of this paper is to review the key advantages of a 3D approach and to highlight potential benefits and limitations. We will be focusing on anatomical details rather than function assessment, and this will be performed with reference to specific lesions. Future developments to overcome remaining limitations will also be discussed.Echocardiography remains a dominant imaging modality in congenital cardiac imaging, due to its accessibility and high temporal and spatial resolution. CT and MRI both hold an integral part in congenital cardiology imaging, with different indications and strengths. One of the major disadvantages of echocardiography is that it relies on the patient’s acoustic windows. It is also restricted by a relatively limited field of view, which means that certain structures, especially extracardiac vasculature, are poorly visualised. CT remains relatively easily accessible compared to cardiac MRI, and can provide good quality images with high spatial resolution with shorter examination times using muti-detector scanners. The main concern with this modality is the use of ionising radiation, although this has been dramatically reduced with latest generation CT scanners. MRI imaging is limited by the need for longer breath holds and the fact that most sequences will need to be gated to the cardiac cycle. This can be challenging in paediatric patients, who might need sedation or general anaesthesia to achieve this successfully. Cardiac MRI, although time consuming and not readily available, remains an excellent radiation-free imaging modality providing robust data, especially for the sequential assessment of cardiac structure and function. The advantages and limitations of each imaging modality are summarised in Echocardiography is frequently the only imaging modality used in congenital cardiac patients, even when surgical repair is required. Conventional 2D echocardiography necessitates mental reconstruction of the 3D image for each cardiac lesion. The way in which images are displayed in 2D is not intuitive to many surgeons and often the appearance does not resemble the anatomy as viewed intraoperatively. The limitations to 2D echocardiography become more evident in complex lesions, especially when compared to CT and MRI data.By using 3D echocardiography, cardiac anatomy is depicted in all dimensions; while retaining adjacent anatomic landmarks to assist with orientation. The major advantage of this is that it provides clinicians with the depth of field that is missing in conventional echocardiography. Furthermore, in contrast to 3D CT and MRI, dynamic motion of the heart, including heart valves, is retained.This provides clinicians with better perspective of cardiac structures and allows for a more accurate evaluation of morphology, relative position, area, circumference and dynamic variation during the cardiac cycle  Figure . This teThere is extensive literature reporting the value of 3D echocardiography in specific congenital cardiac defects. It has proven most helpful for the evaluation of the mitral valve where it provides physiologic, morphologic and functional assessment . Three-dSimilar advances have been noted in the management of AVSD spectrum defects, features of which are sometimes difficult to appreciate in 2D imaging . Three-dThere is also a clear role for 3D echocardiography in delineating anatomy and surgical planning in patients with double outlet right ventricle; when the ventricles are balanced and a biventricular repair remains the desired approach . Three-dThe use of 3D echocardiography in patients with complex left ventricular outflow tract obstruction can provide additional details on the obstructive substrate . Volume 3D TOE provides additional information during elective or pre-procedural imaging of selected patients and has led to advances in interventional procedures. There is an ever-growing group of TOE-guided procedures where 3D echocardiography facilitates both appropriate patient selection and also intra-procedural guidance and decision making. Real-time 3D imaging is recommended for visualization of catheters, delivery systems, and identifying device position, any residual shunt and the relationship of the device to adjacent structures . Three-dSimilarly, 3D TOEs are used to guide percutaneous VSD closure as well as paravalvar and baffle leak closure, where an ‘en face’ view of the defect is feasible, making the location of the leak more easily identifiable  Another CT provides extremely high-resolution cardiovascular imaging, including 3D rendered views, with the most recent generation of ultrafast scanners reducing both scan time and radiation dose. This facilitates high-resolution imaging in the context of un-cooperative or unstable patients, for example in an intensive care setting. However, CT still uses ionising radiation and paediatric patients are likely to need repeat imaging and their rapidly dividing cells make them more susceptible to radiation damage . It is aCT offers the option of both surface and volume rendering, with surface rendering using only part of the available data for 3D reconstruction . After tThe main advantage of CT is the imaging of complex vascular structures. In patients with Tetralogy of Fallot, 3D CT data demonstrates pulmonary arterial distribution, with the anatomy of the right ventricular outflow tract and any potential coronary artery anatomy variations precluding or complicating surgical or interventional procedures. Three-dimensional CT imaging provides a comprehensive delineation of the pulmonary blood supply in patients with pulmonary atresia and major aortopulmonary collaterals, allowing for the planning of unifocalisation and pulmonary artery reconstruction. Three-dimensional aortic arch reconstructions can accurately demonstrate the arch anatomy and length of the narrowed segment in complex cases of coarctation, as well as the relationship with head and neck vessels . The inc3D MRI acquired data can produce whole heart imaging and visualise the extracardiac vasculature and relationships to adjacent structures while remaining free of radiation. Contrast-enhanced angiography and non-contrast enhanced 3D whole heart imaging can be used as required to interrogate cardiac anatomy on a multiplanar reformat platform . A new oThe recent development of 4D flow MRI includes a phase contrast MRI study with flow encoding in all three spatial directions relative to all three dimensions of space and to the dimension of time throughout the cardiac cycle  Figure . This alSimulations using computational fluid dynamics (CFD) derived from MRI data and patient-specific 3D models offer the possibility for modelling circulation in congenital heart defects, and can provide measures of flow and how these would be affected by interventions that change the geometry . A cliniThree-dimensional printing is used in patients with congenital heart disease to precisely visualise complex anatomy, and to depict complex intracardiac spatial relationships . The maj3D printing is useful in defining the most appropriate surgical management in specific cardiac lesions. A landmark multi-centre European study has demonstrated a change in the management or surgical approach after a 3D model was reviewed in 19 out of 40 complex cases, when compared to multidisciplinary consensus prior to access to the model . In 10 oThere is currently no imaging modality that can demonstrate all the anatomical features necessary in complex lesions to guide surgical planning. A 3D hybrid printed model combing MRI/CT and 3D echocardiographic data can provide diagnostic information superior to individual imaging modalities and aid in hands-on simulations of the optimal surgical approach in challenging cases such a straddling AV valves . CombiniAntenatal detection of congenital heart disease has become increasingly common with the development of appropriate foetal screening, including more extensive visualisation of the great arteries in the upper mediastinum. This is based on 2D foetal echocardiography, which can sometimes be challenging, due to certain foetal and maternal factors. Three- and four-dimensional foetal echocardiographic techniques, such as spatiotemporal image correlation imaging (STIC), can be extremely helpful for more complex lesions such as double outlet right ventricle  or vascuStandard 2D foetal (cardiac) MRI is susceptible to foetal and maternal motion . Novel tWe have already highlighted the advantages of 3D TOE in guiding percutaneous procedures. Three-dimensional echocardiography has also allowed for fusion imaging, where the echocardiographic and fluoroscopic images are synchronised and displayed in the same visual perspective to provide a better spatial relationship of the intracardiac anatomy . The TOEThe feasibility and spatial accuracy of pre-procedural 3D CT and MRI images to 3D rotational fluoroscopy registration to guide interventional procedures in patients with congenital heart disease has also been investigated. This technology displays great potential in integrating three-dimensional imaging in the catheterisation laboratory to reduce procedure time, radiation and contrast dose . AssessiExtended reality (XR) denotes any technology combining a computer-generated environment with the real world, and is usually represented as a spectrum, from complete immersion in a digital world to physical reality . It encop < 0.05) and an improved delineation of anatomy in 34 patients with DORV, where a pre-operative XR review of CT imaging was performed [XR holds great potential for the planning of surgical and catheter procedures in congenital heart disease, where an understanding the spatial relationships of structures is key. Ye et al. demonstrated a reduced planning time  was used to display CT imaging during 17 complex pulmonary artery surgical repairs in children . This st3D models can facilitate interventional planning by allowing interventionalists to simulate and size percutaneous valves or occluder devices, when the commercially available sizes have not been ideal. This applies to septal defects, but is particularly useful in patients with Tetralogy of Fallot, where the dilation of the right sided structures can pose technical challenges to valve implantation , as wellPatient-specific 3D printed models have been used in the development of new techniques, such as the transcatheter correction of sinus venosus ASD and partially anomalous pulmonary venous return via the implantation of a covered stent . SuitabiA new technique providing personalised external aortic root support in patients with Marfan’s syndrome has also been made feasible, using spatial MRI and CT data to create a computer aided design and a physical model for each individual patient . A repli3D cardiac imaging, and especially printed models, appear to be gaining an integral role in surgical and interventional training. These models provide a great tool for simulation, allowing surgeons to practice surgical techniques and expose them to a variety of congenital defects in a structured away, instead of leaving all of the technical training to the operating theatre. There is data suggesting a significant reduction in time required for specific procedures after performing simulation surgeries in 3D models .The role of these models extends to the teaching of healthcare professionals, including nurses and doctors in training. Having access to these physical or digital replicas of the cardiac anatomy has been shown to be a great educational tool, offering experiential learning to medical personnel. Recently, an open-source library to share stereolithography files, ready to print across all of the Association for European Paediatric and Congenital Cardiology members has been created, providing access to a wide spectrum of cardiac pathologies .Three-dimensional models have also been used when counselling patients, with a proven enhancement in patient’s understanding and subsequent compliance without impacting on clinical workflow . PatientThere are clear benefits that have already been highlighted with regard to the use of 3D cardiovascular imaging. It provides the depth of field needed to fully appreciate the cardiac anatomy, and it allows users to interrogate live or saved images while providing the opportunity to re-interrogate stored data, as clinically indicated. It is a valuable educational tool, providing a new insight into congenital lesions and facilitating a more user-friendly method of imaging the heart without the need for a mental 3D reconstruction of the conventional 2D image.One of the main challenges of 3D echocardiography is the current lack of consistency in image orientation, although there are guidelines in place. Using the same alignment as is used with other imaging modalities, and to display images in an anatomically correct orientation is recommended . The cohThere are also additional considerations in children, such as higher heart/respiratory rates and overall smaller cardiac structures. Three-dimensional echocardiography might be technically more challenging, due to a lack of co-operation, with some patients requiring sedation to achieve optimal imaging with no stitch artifact. While higher frequency probes are recommended for children, 3D imaging is usually acquired with wider bandwidth adult probes, whose footprints and lower frequencies might be suboptimal for these patients . The aboOne of the limitations of 3D printing is that it remains an expensive imaging technique, currently used in specialised congenital cardiac centres, and requiring in depth training and specific expertise and resources. With appropriate protocol modifications, it seems possible to print high-quality and affordable 3D printed cardiac models that have been useful for improving the quality of care of the patients . There a3D printed models are not dynamic and cannot be re-cropped once produced. With respect to their use in catheter interventions, they do not respond to balloons and stents in the same way as native tissue, and they cannot accurately represent the physiological settings of these procedures . It mighAlthough the introduction of 3D cardiovascular imaging has enhanced our understanding of congenital heart disease, there remain areas where further comprehension is required to optimise patient management. Three-dimensional imaging has offered a new insight into our understanding of the mechanism of tricuspid valve regurgitation in hypoplastic left heart syndrome ,67. SimiOne of the current limitations of 3D TOE in the paediatric population is the size of the adult 3D probe, which can be used ideally in patients >25kg. The development of paediatric miniaturised 3D TOE probes will enable the use of this modality in more patients, and could result in more TOE-guided procedures. This pitfall might also be addressed via the use of intracardiac echocardiography, a modality that is increasingly being adopted to guide percutaneous cardiac structural interventions. This was previously limited by the presence of only two-dimensional imaging planes, but a three-dimensional system has been assessed with encouraging results in procedure guidance . AdditioThere is a constant evolution of 3D printing technologies, as well as the materials used. With the help of tissue engineering, biocompatible and human-like tissue materials are currently being developed. Surgical patches and parts of the heart are close to being manufactured, while aiming to be able to fabricate complete and functional hearts .There is no doubt that the use of 3D imaging has resulted in high quality imaging in congenital heart disease, as well as a better understanding of structural abnormalities. What still remains to be answered is whether the introduction of this additional dimension is consistently leading to better patient outcomes. A patient-specific surgical approach could result in shorter cardio-pulmonary bypass times, shorter postoperative stays, decreased reintervention rates and lower health care costs . Robust


On age and sex adjusted regression analysis, lower liver HU values indicated a dismal cardiometabolic risk profile, including higher HbA1C (p = 0.005) and higher body mass index (p < 0.001). In contrast, native hepatic T1-times yielded a more pronounced cardiac risk profile, including impaired systolic function (p = 0.045) and higher NT-proBNP values  (p = 0.004). Conclusions: Hepatic T1-times are easy to assess on standard T1-maps on CMR but only weakly correlated with hepatic HU values on CT and clinical NAFLD/MAFLD scores. Liver T1-times, however, are linked to impaired systolic function and higher natriuretic peptide levels. The prognostic value and clinical usefulness of hepatic T1-times in CMR cohorts warrants further research.Background: Non-contrast computed tomography (CT) is frequently used to assess non-alcoholic/metabolic fatty liver disease (NAFLD/MAFLD), which is associated with cardiovascular risk. Although liver biopsy is considered the gold standard for diagnosis, standardized scores and non-contrast computed tomography (CT) are used instead. On standard cardiac T1-maps on cardiovascular imaging (CMR) exams for myocardial tissue characterization hepatic tissue is also visible. We hypothesized that there is a significant correlation between hepatic tissue T1-times on CMR and Hounsfield units (HU) on non-contrast CT. Methods: We retrospectively identified patients undergoing a non-contrast CT including the abdomen, a CMR including T1-mapping, and laboratory assessment within 30 days. Patients with storage diseases were excluded. Results: We identified 271 patients  undergoing non-contrast CT and CMR T1-mapping within 30 days. Mean hepatic HU values were 54 ± 11 on CT and native T1-times were 598 ± 102 ms on CMR and there was a weak, but significant, correlation between these parameters (r = −0.136,  Metabolic dysfunction associated, or fatty, liver disease  describes a continuum of hepatic diseases ranging from steatosis to liver cirrhosis. MAFLD/NAFLD is the most prevalent liver disease, affecting one in four individuals in a Western population. So far, no treatment is available . MAFLD/NDespite its high prevalence and clinical importance, the diagnosis of MAFLD/NAFLD is challenging. Liver biopsy represents the gold standard for MAFLD/NAFLD diagnosis but is infrequently performed due to its invasive nature. Alternatively, the NAFLD Fibrosis score (NFS)  and FibrMoreover, non-invasive imaging is frequently used to estimate the risk for MAFLD/NAFLD. Non-contrast computed tomography (CT) and magnetic resonance imaging (MR) aim to detect hepatic tissue signal and liver stiffness alterations due to increased fibrosis ,6. CT isSeveral factors have been proposed to promote MAFLD/NAFLD, many of which play an important role in CVD, including endothelial dysfunction, altered lipid metabolism, systemic inflammation, oxidative stress, and systemic insulin resistance ,9.In patients with CVD, cardiovascular magnetic resonance imaging (CMR) is evolving as the first-line imaging technique as it is the gold standard for structural and functional assessment of the heart. In addition, cardiac tissue characterization by T1-mapping provides novel insights into pathological alterations within the myocardium ,11. ThusPreclinical data  and one This was a retrospective study in a single tertiary referral center. Using our hospital-wide electronic system, we identified individuals who had undergone within 30 days: (1) non-contrast CT scans including the abdomen allowing for hepatic tissue assessment, and (2) CMR including T1-mapping where hepatic tissue is visualized in a standard mid-cavity short-axis slice . The insAt the time of CMR and CT, demographic data  and comorbidities were assessed. These included hypertension (≥140/90 mm Hg or antihypertensive treatment), atrial fibrillation , diabetes , hyperlipidemia , smoking status, coronary artery disease (CAD), previous percutaneous coronary intervention, and previous coronary artery bypass grafting (CABG). Previous myocardial infarction was defined both by medical history and CMR. The estimated glomerular filtration rate was calculated with the simplified Modification of Diet in Renal Disease formula . In addi2.All patients underwent CMR examinations on a 1.5-T scanner  following standard protocols that included late gadolinium enhancement (LGE) imaging [0.15 mmol/kg gadobutrol ] if the estimated glomerular filtration rate was >30 mL/min/1.73 mT1 mapping was performed with electrocardiographically triggered MOLLI (Modified Look-Locker Inversion Recovery) using a 5(3)3 prototype (5 acquisition heartbeats followed by 3 recovery heartbeats and a further 3 acquisition heartbeats) on a short-axis mid cavity slice and with a 4-chamber view. This method generates an inline, pixel-based T1 map by acquiring a series of images over several heartbeats with shifted T1 times, inline motion correction, and inline calculation of the T1 relaxation curve within one breath. T1-sequence parameters were as follows: starting inversion time (TI) 120 ms, TI increment 80 ms, reconstructed matrix size 256 × 218, measured matrix size 256 × 144 . T1 maps were created both before and 15 min after contrast agent application.Hepatic T1-times were measured using an average of three measures with sufficient distance to vessels and the bile duct . MyocardCT scans were performed on 64-MDCT (Multi-Detector Computed Tomography) scanners at 100–120 kV with automatic tube current modulation and 5 × 3 mm reconstructions . We only used the unenhanced images for assessment of liver attenuation. We defined three regions of interest on an axial single slice, two placed in the right liver lobe and one in the left liver lobe. The regions of interest had a maximum diameter of approximately 1 cm and regions close to vessels or the bile duct were avoided. The distance to the Glisson’s capsule was a minimum of 2 cm. We used an average of these three measurements.2]) +  + (0.99 × AST/ALT ratio) – (0.013 × platelet count [×109/L]) – . Results were stratified by the cut-off values < −1.455 (mild to moderate fibrosis), −1.455 to 0.675 (indeterminant score), and a score of >0.675 (severe fibrosis or cirrhosis) [The NFS was calculated with its formula: NFS = −1.675 + (0.037 × age [years]) + (0.094 × BMI (Body Mass Index) b [kg/mrrhosis) .All statistical analyses were computed using Stata 15. Continuous data are expressed as mean ± standard deviation or median with corresponding interquartile range, and categorical variables are presented as percentages or total numbers. We used intraclass correlation coefficients (ICC) to assess inter-rater variability, for which a second, blinded reader performed measurments on 50 randomly chosen patients.Pearsons’s correlation coefficients were used to assess an association between liver attenuation on CT and T1-mapping. The association between native hepatic T1-times and established markers of cardiac risk, including left and right ventricular ejection fractions  and NT-proBNP was tested using age and sex adjusted regression analysis.For all analyses, the level of significance was set to 0.05.n = 77, 28%), left ventricular hypertrophy , assessment of valvular heart disease , coronary artery disease , myocarditis , and others .We identified 1045 individuals undergoing native CT and CMR, of whom 135 were excluded due to inadequate imaging quality. Out of the remaining 910 patients, 271 individuals underwent CT and CMR within 30 days, forming our final study cohort. Indications for CMR were heart failure (p = 0.03) . Overall, we found a weak but significant correlation between hepatic tissue characterization on CMR and CT  see p = 0.003) and a higher NFS (p = 0.008) when compared to patients with HU values above the median. This was not observed for hepatic T1-times on CMR. However, in contrast to CT HU values, patients with T1-times above the median were more often in atrial fibrillation  and had higher gGT values .p = 0.025), AST/GOT  (p = 0.011), gGT (p = 0.002), and NT-proBNP (p = 0.004), LVEF (p = 0.045), RV (Right Ventricle) size and function , p = 0.005), LA size (p < 0.001), and myocardial native T1-times (p < 0.001).In age- and sex-adjusted linear regression models see , we founp < 0.001), HbA1C (p = 0.005) and the NFS (p = 0.014), none of which were associated with native hepatic T1-times. None of the conventional CMR parameters, including LV and RV size and function were associated with liver HU values on CT.Interestingly, regression models showed a different pattern of association with baseline variables when comparing native HU values on CT and CMR. For CT, regression models revealed an association with BMI (We report three main findings in this exploratory study of patients undergoing non-contrast CT and CMR within 30 days: (1) liver HU values on CT and native hepatic T1-times on CMR only correlate weakly with each other, (2) liver HU values on CT are associated with cardiometabolic traits, such as diabetes and the NFS, and (3) in contrast, hepatic T1-times on CMR are associated with impaired cardiac function, including LVEF, RVEF, and natriuretic peptide levels.In patients with CVD, liver damage is frequently observed but is rarely assessed. Two clinical scenarios are most commonly discussed as causes for liver damage in these patients: (1) congestion due to cardiac backward failure, and (2) MAFLD/NAFLD, which is the most rapidly increasing cause of liver-related mortality worldwide and is strongly associated with risk for cardiovascular disease .Cardiac backward failure as a cause for liver damage can easily be identified by cardiovascular imaging using CMR, allowing for assessment of left and right ventricular function, and surrogates of filling pressures, such as left atrial size. Moreover, T1-mapping of the left ventricle on CMR further enhances our understanding of cardiac dysfunction caused by diffuse alterations within the myocardium , which m18FDG-PET) image analysis, cardiac glucose uptake was significantly decreased in participants with MAFLD/NAFLD [In addition to heart failure as a cause for liver damage, MAFDL/NAFLD is highly prevalent in patients with cardiovascular diseases . The diaLD/NAFLD . Taken tLD/NAFLD . HoweverLD/NAFLD .Both CT and CMR are routine imaging techniques in patients with CVD. T1-mapping is now routinely applied in patients undergoing CMR and would also allow for liver tissue assessment as it is frequently displayed on standard cardiac T1-maps. However, hepatic T1-mapping in patients undergoing CMR has never been correlated with HU values on CT. Few studies report on T1-times of the liver in patients with CVD. In line with our findings, that native hepatic T1-times are associated with LV systolic dysfunction in a study by Isaak and Praktiknjo et al. on 60 participants receiving a liver MR and a CMR. They demonstrated that participants with greater severity of liver disease also displayed more severe systolic dysfunction, and increased myocardial T1-times . SimilarWe could show that results from non-contrast CT and T1-mapping on CMR may represent different aspects of liver damage in patients with CVD. Whereas CT detects a cardiometabolic trait with higher prevalence of diabetes and higher NAFLD score , higher native hepatic T1-times are associated with a dismal cardiac risk profile, including impaired left and right ventricular ejection fraction, enlarged left atrial size, and higher natriuretic peptide levels. Future research is warranted to investigate the underlying processes detected on hepatic T1-mapping and whether it may be useful for improved risk prediction in patients with established CVD.Several limitations merit comment. Firstly, the single center study and the retrospective nature may result in a biased cohort and results may not be generalized to other cohorts. Secondly, T1-times reflect composite alterations within the tissue and T1-mapping results do not allow for a direct conclusion about pathophysiological processes. Of note, in NAFLD/MAFLD both fat accumulation and fibrosis play a crucial role, however, fat lowers native hepatic T1-times whereas fibrosis leads to an increase in T1-times. This may explain the weak correlation between CT and CMR tissue characterization findings. Hence, changes in T1-time in the liver may be a result of several components, which could only be confirmed by invasive biopsy.Hepatic T1-times are easy to assess on standard T1-maps on CMR but only weakly correlated with hepatic HU values on CT and clinical NAFLD/MAFLD scores. Hepatic T1-times, however, are linked to impaired systolic function and higher natriuretic peptide levels. The prognostic value and clinical usefulness of hepatic T1-times in CMR cohorts warrant further research.


The right ventricle (RV) in hypertrophic cardiomyopathy (HCM) tends to be neglected, as previous efforts have predominantly focused on examining the prognostic value of left ventricular (LV) abnormalities. The objectives of this study were to assess RV function in HCM, changes over time, and association with clinical outcomes.Two hundred and ninety HCM patients with preserved LV ejection fraction (LVEF ≥ 55%) and 30 age- and sex-matched controls underwent cardiovascular magnetic resonance (CMR). All patients were followed up for clinical events for a median duration of 4.4 years. Sixty-three patients had a follow-up CMR undertaken at a median interval of 5.4 years. Main study measures and outcomes were RV function (RV ejection fraction (RVEF) and RV strain) at baseline, temporal changes in RV function over time and prognostic value of RV dysfunction for predicting cardiovascular outcomes in HCM.When compared to controls, HCM patients exhibited lower RV and LV peak global longitudinal systolic strains on feature-tracking analysis of cine images, while RVEF and LVEF were within the normal range. On follow-up CMR, both RV and LV strain parameters decreased over time. RVEF decreased at follow-up  but the change in LVEF was not significant . On clinical follow up, reduced RVEF was an independent predictor of non-sustained ventricular tachycardia (NSVT)  and composite cardiovascular events  . RV longitudinal strain was an independent predictor of NSVT . Patients with RVEF < 55% showed an increased risk of NSVT and composite cardiovascular events. In contrast, LVEF and LV global longitudinal strain were not predictive of such events on multivariable analysis.In HCM, RV function, including RV strain, and LV strain decrease over time despite preserved LVEF. Reduction in RV but not LV function is associated with adverse cardiovascular outcomes. Assessing RV function in early HCM disease might have a role in risk stratification to prevent future cardiovascular events.The online version contains supplementary material available at 10.1186/s12968-022-00868-y. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease with an estimated prevalence of 1 in 500 –4. IdentRV dysfunction has been shown to predict adverse outcomes in a number of other cardiovascular diseases. For example, in a study of HF patients with preserved LV ejection fraction (HFpEF) , RV funcRV functional assessment has improved considerably with the use of cardiovascular magnetic resonance (CMR) in clinical practice. When compared to echocardiography, CMR provides comprehensive views of the RV at high resolution with superior blood-myocardium discrimination. In addition, advanced post-processing analysis of cine-images such as quantitative myocardial strain analysis has permitted further characterisation of RV function .In this study, we sought to characterise RV function comprehensively using CMR (RV ejection fraction (RVEF) and RV strain) in HCM patients with preserved LV function. We further examined the temporal changes in RV function over time and investigated the prognostic value of RV dysfunction for predicting cardiovascular outcomes in HCM.HCM patients aged > 18 years, without LV impairment were enrolled from the Inherited Cardiac Conditions (ICC) clinic at the Oxford University Hospitals NHS Foundation Trust (2003–2016).These patients had either a genetic diagnosis of HCM and LV wall thickness of ≥ 13 mm, or non-familial HCM patients with a LV wall thickness ≥ 15 mm, but no other cause of hypertrophy identified [All patients underwent CMR imaging at 1.5 T or 3 T CMR scanners . Cine imaging was performed using standard methods, acquiring images in the short axis (SAx), axial and horizontal long axis (HLA) planes . RV voluHCM patients were followed up with (1) ICC clinic visits at regular intervals of 6 months to 1 year, (2) hospital records for encounters with health services and (3) telephone interview for cases that were not followed up in Oxford. Follow up CMR scans were done as part of an ethically approved prospective research study (reference: 12/LO/1979). Funding to support follow-up scans  were only available for 63 patients. Patients were invited randomly by a clinical research fellow who had no prior knowledge of disease severity or symptoms status. All patients were part of a genetic research database Progeny ICC and had agreed to be contacted for future research. Clinical events during the follow-up period were recorded, and arrhythmic events were verified by reviewing 24-h Holter reports. Clinical events included new onset atrial fibrillation (AF), ≥ 3 beats of non-sustained ventricular tachycardia (NSVT) at a rate of ≥ 120 beats/min, stroke or embolic event, HF outcomes which included HF hospitalisation and progression to New York Heart Association (NYHA) class III/IV, and all-cause mortality. The combination of incident AF, NSVT, HF outcome, and cardiovascular death was used as composite cardiac end-point.Categorical variables are summarised as proportions (%) and analysed using chi-square test where appropriate. Continuous variables are presented as means ± standard deviation for normally distributed data. Variable were tested for normality with Kolmogorov–Smirnov statistics for normal distribution. Student t-test was used for comparisons of quantitative measurements between HCM and healthy controls. Paired t-test was used to analyse interval changes in CMR measurements. Pearson correlation analysis was used to study the relationships between RVEF and strain results. Outcome and survival data were analysed using Cox proportional hazards regression model and presented as Kaplan–Meier curves. Univariate and multivariable binary Cox regression model was used to estimate the hazard ratio (HR) for RVEF, RV strain and LVEF, LV strain  and 30 healthy controls  are summarised in Table CMR results are shown in Table In 63 patients , serial CMR was undertaken at a median interval of 5.4 years (interquartile range 4.2–7.1 years) and results are shown in Table During a median of 4.4 years of follow up (interquartile range 2.9–6.6 years), 5 patients were lost to follow up. 73 (24%) patients had incident arrhythmias including NSVT  and AF , including one patient who had both. Sixteen (5%) patients had a HF outcome and 7 (2%) patients had a stroke. Seven (2%) patients died, of which 2 deaths were attributed to a cardiovascular cause. Thirty patients (11%) had ICD implantation for primary prevention. There were no SCDs nor appropriate shocks delivered by defibrillators.On univariate analysis, both LV global longitudinal strain and LVEF were predictive of NSVT and composite cardiac events on univariate analysis. Additionally, LV global longitudinal strain was also predictive of AF, HF progression and all-cause mortality. The association was lost on multivariable analysis after adjusting for the respective univariate predictors , there was a three-fold increase in NSVT  and a two-fold increase in composite cardiac events  on univariate analysis as shown in Fig. We further examined the prognostic role of RV function in determining composite events and NSVT in patients under 55 years old. RVEF remained predictive of both composite cardiac outcomes and NSVT in patients ≤ 55 years and above.The current study shows three important findings. First, RV and LV strains were impaired in patients with HCM despite normal LVEF. There was a small reduction in RVEF, albeit within accepted normal limits. Second, whilst LVEF remained stable, both RVEF and RV strain, as well as LV strain parameters progressively declined in HCM over time. Third, RVEF was an independent predictors of adverse cardiovascular outcomes even after adjusted for conventional LV parameters such as LV wall thickness and LGE.Whilst both morphological and functional changes of the LV have been well characterised in HCM, less is known about the RV function owing to difficulties encountered during assessment of the RV, arising from its complex geometry . Two-dimIn the present study, we showed that despite normal LVEF, RV function, in particular RV strains in HCM patients were significantly reduced, with a small reduction in RVEF although this was still within the normal range, for an age- and sex-matched controls. We also showed that LV strain parameters were reduced in line with a previous study . Our finAlthough the mechanisms underlying RV dysfunction in HCM are unclear, previous studies have reported histological evidence of hypertrophy, myocyte disarray and fibrosis involving the RV of HCM patients . Indeed,Myocardial strain is a sensitive tool for the assessment of subclinical cardiac dysfunction on both echocardiogram and CMR . AlthougThis study also examined the natural history of RV dysfunction on interval CMR scans in a subset of patients. We found a significant decrease in RVEF and longitudinal strain, but not circumferential or radial strain. Interestingly, the reduction in RVEF was not accompanied by a parallel reduction in LVEF, though LV global longitudinal strain did decrease over time. This would suggest that RVEF may be more sensitive than LVEF to disease progression . We haveIn this study, clinical follow up of 290 HCM patients was undertaken over a median interval of 4.4 years. Previous studies have found RV hypertrophy to be prognostically important. Here, although maximum RV wall thickness was a determinant of HF outcomes on univariate analysis, there was no association seen with ventricular arrythmias. Additionally, in our study the relationship between RV wall thickness and HF progression was lost after adjusting for RV function and other univariate predictors. The presence of LGE in the RV also did not associate with clinical outcomes and is likely to reflect the reduced power of this study owing to the low frequency of RV LGE. On the other hand, reduced RVEF was predictive of NSVT and composite cardiovascular events , while RV global longitudinal strain was predictive of NSVT even after adjusting for confounding variables . These findings are consistent with a recent study by Shah et al.  which shAnother interesting observation was the association of RVEF with NSVT and composite cardiovascular events in those under the age of 55. Ho et al.  have simThe limitations of this study follow from its observational, single-centre study design. The population studied were at low risk for SCD and some of the endpoints (NSVT and AF) chosen, although clinically relevant, were soft. Furthermore, details about the number of ventricular triplets of NSVT, which on its own is a soft end point were not available. The echocardiographic analysis of the RV was performed as per clinical need, therefore targeted RV acquisition may have been suboptimal, particularly early on in the enrolment period before the publication of American Society of Echocardiography (ASE) guidelines for evaluation of the right heart in 2010 . The lacIn HCM, RV function, including RV strain, and LV strain may decline over time despite stable LVEF. Reduced RVEF is associated with NSVT and composite cardiovascular events, while global longitudinal strain is associated with NSVT. RV function may be more sensitive than LV functional parameters for disease prognostication at an early stage. These findings warrant large-scale assessment of RV parameters as risk predictors in HCM.Additional file1 .Additional file2 .