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.

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.

Thrombin Generation and other hemostatic parameters in patients with atrial fibrillation in use of warfarin or rivaroxaban.

Patients with atrial fibrillation (AF) present hyperactivation of both platelets and coagulation leading to a hypercoagulable state which contributes to an increased risk of thromboembolism. Therefore, one of the main strategies for treatment of AF is prevention of these events through the use of oral anticoagulants (OAC). The aim of this study was to evaluate hemostasis as a whole in patients with non-valvular AF undergoing warfarin or rivaroxaban by thrombin generation test (TGT), in addition to monocyte-platelet aggregates (MPA), glycoprotein IIb/IIIa (GPIIb/IIIa), and platelet (PMP) and endothelium (EMP) microparticles, compared to age and sex matched controls. PT/INR for OAC use was also determined. In patients taking OAC, compared to control group, a decrease in TGT (p = 0.000 for all parameters) were observed. Patients taking warfarin showed to be more hypocoagulable, presenting lower levels of ETP (p = 0.000) and peak (p = 0.002) than patients using rivaroxaban. Patients on warfarin use with INR > 3 had also lower levels of ETP (p = 0.01) and peak (p = 0.006). A decrease in ETP (p = 0.03) and peak (p = 0.02) values was also observed in patients using rivaroxaban with PT > 21.4 s. Patients using warfarin (p = 0.000) and rivaroxaban (p = 0.000) presented lower levels of MPA in relation to control group. It was also observed in patients using warfarin, lower GPIIb/IIIa levels in relation to control group (p = 0.011). Patients taking rivaroxaban (p = 0.003) and warfarin (p = 0.001) had higher PMP levels compared to control group. There was no difference in levels of EMP between the groups (p = 0.0536). The present study reinforces the usefulness of OAC in AF, which decisively contribute to a better management of the disease preventing possible complications.

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.

Unusual variants of pre-excitation: From anatomy to ablation: Part I-Understanding the anatomy of the variants of ventricular pre-excitation.

The famous quotation of Winston Churchill, made in his radio broadcast of 1939 regarding Russia's next move, specifically "A riddle wrapped up in a mystery, inside an enigma," perfectly fits the current understanding of unusual accessory atrioventricular pathways, including the variants producing ventricular pre-excitation. It was many decades after their original descriptions that we came better to begin to understand most of their structure-function relationships. Their mysterious pathophysiology was sometimes unveiled after invasive treatments, such as surgical ablation of the atrioventricular conduction axis instead of the accessory pathway itself. Speculations made on this basis have largely been validated by subsequent clinical experience. Most of the names suggested for description of the pathways have stood well the test of time. For some of them, however, this is not the case, with the initial names becoming confusing. In a series of reviews, we re-visit those accessory pathways producing ventricular pre-excitation other than classical Wolff-Parkinson-White syndrome. To set the scene, in this initial review, we describe the development and anatomy of the normal atrioventricular conduction axis, along with the insulating tissues of the atrioventricular junctions. We have sought to illustrate our explanations by using virtual dissection of computerized tomographic datasets, since they retain the intact heart within the setting of the body. These images illustrate well the value of attitudinally appropriate terminology. Thereafter, we discuss the electrophysiological manifestations of the abnormal anatomical pathways which provide the potential for both accessory atrioventricular and intraventricular conduction.

Reappraisal and new observations on atrial tachycardia ablated from the non-coronary aortic sinus of Valsalva.

Aims: The clinical characteristics of atrial tachycardias (AT) ablated from the non-coronary aortic sinus (NCS) are thus far described only in small series. We aimed to outline, in a large cohort of patients, the clinical, electrocardiographic, electrophysiological characteristics of this tachycardia. Methods and results: We analysed data pertaining to clinical, electrocardiographic, and electrophysiological characteristics of 43 consecutive patients from an overall cohort of 441 with AT who were successfully ablated from the NCS. The tachycardias ablated from the NCS were paroxysmal (98%) and adenosine sensitive (35/35). The patients were aged 54.6 ± 12.4 years, showing female preponderance (74%). No P wave pattern was predictive of the location of ablation. Electrophysiological findings suggested a possible micro-reentrant mechanism. During tachycardia, atrial electrograms recorded in the NCS preceded the A in the His region by 10.9 ± 7.4 ms. Fractionated atrial electrograms were noted at the site of ablation in 42 patients during the tachycardia. Radiofrequency ablation terminated the tachycardia within 5 s in 88%, with thermal automaticity seen only in 3 patients. The site of ablation at the base of the NCS was adjacent to the presumed site of the retroaortic node, a remnant of the initial atrio-ventricular canal musculature. Conclusions: AT ablated from the NCS is a paroxysmal arrhythmia in middle-aged women, with distinct electrocardiographic and electrophysiological characteristics. We suspect the retroaortic node to be involved in the tachycardia circuit.

Is the 12-lead electrocardiogram during antidromic circus movement tachycardia helpful in predicting the ablation site in atriofascicular pathways?

AIMS: Unlike in the Wolff-Parkinson-White syndrome, there has been no systematic study on the role of the pre-excitation pattern in predicting the ablation site in patients with atriofascicular (AF) pathways. We assessed in a large cohort the value of the 12-lead electrocardiogram (ECG) during antidromic tachycardia (ADT) to predict the site of ablation. METHODS AND RESULTS: Forty-five patients were studied, 23 males (51%), mean age of 27 ± 12 years with 46 AF pathways and 48 ADT using the AF pathway for A-V conduction. Inclusion required induction of a sustained ADT and successful ablation. Ablation site was assessed during LAO 45° projection and clockwise classified as hours in posteroseptal, posterolateral, lateral, anterolateral, and anteroseptal tricuspid annulus as follows: 05:00-07:00, >07:00-08:00, >08:00-09:00, >09:00-11:00, and >11:00-13:00 o'clock. The QRS axis was assessed during ADT and classified as normal (>+15°), horizontal (+15° to -30°), and superior (<-30°). During ADT axis was superior (-57° ± 10°) in 15 (31%), horizontal (-11° ± 14°) in 22 (46%), and normal (+45° ± 16°) in 11 (23%) patients. The correct ablation site did not differ between the different groups of QRS axis. QRS width during ADT was narrower in patients with a normal when compared with a horizontal and leftward axis (127 ± 14 vs. 145 ± 12 ms, P < 0.0001), and the V-H interval was shorter (4 ± 3 ms vs. 19 ± 22 ms, P = 0.03). CONCLUSIONS: There was no correlation between the AF pathway ablation site and the QRS axis during ADT. The 12-lead ECG during maximal pre-excitation does not predict the proper site of tricuspid annulus ablation in patients with A-V conduction over an AF pathway.

Outcomes with physiologic His bundle pacing in patients with narrow QRS complex.

BACKGROUND: In patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. OBJECTIVE: This study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. METHODS: In 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. RESULTS: The paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. CONCLUSION: In patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.

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.

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.

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.

Electrical storm originating from a left ventricular epicardial scar in a patient with completely normal endocardial voltage.

We report a patient with non-ischemic dilated cardiomyopathy presenting with an electrical storm because of a poorly tolerated monomorphic ventricular tachycardia. Electroanatomical mapping revealed a scar restricted to the epicardium, whereas the endocardial voltage map was completely normal. Epicardial catheter ablation based on substrate mapping and limited pace and entrainment mapping eliminated the tachycardia.

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.

Glycogen storage cardiomyopathy (PRKAG2): diagnostic findings of standard and advanced echocardiography techniques.

AIMS: Describe the findings obtained using standard echocardiography (Echo) and deformation indices (2D and 3D speckle tracking strain) in patients (Pts) with PRKAG2 cardiomyopathy. Seek to identify any peculiar characteristics and possible strain patterns that may distinguish this condition from other causes of left ventricular hypertrophy (LVH). METHODS AND RESULTS: Thirty Pts with genetically proven PRKAG2 (R302Q and H401Q), 16 (53.3%) male, mean age 39.1± 15.4 years old, were examined using standard, speckle tracking (STE), and 3D Echo. Pacemaker (PM) had been implanted in 12 (40%) Pts with a mean age of 38.1 ± 13 years. Hypertrophy was found in varying degrees in 18 (86%) Pts. Seven Pts (24%) presented 3D ejection fraction (EF) below normal limits. Diastolic function was abnormal in 17 (63%) Pts. Global longitudinal strain (GLS) on 2D measured -16.4% ± 5.3%. GLS measured -13.2% ± 4.8%, global radial strain 40.8% ± 13.8%, global circumferential strain (GCS) -16.1% ± 4.4%, and global area strain -26.1% ± 6.7% by 3D Echo offline analyses. Pts with PM presented lower EF and GCS compared with those without PM. EF/GLS measured 3.65 ± 1.00. In the bull's eye map, a strain pattern similar to stripes in 18 (60%) Pts was identified, which might be a differentiating signal among LVH. CONCLUSION: Echocardiography is a valuable tool in detecting diffuse and focal myocardial abnormalities in PRKAG2 cardiomyopathy. The deformation indices are especially revealing because they may help distinguish this rare infiltrative disease, thereby favouring early diagnosis, enhanced treatment, and improved outcome.

Inferior Extensions of the Atrioventricular Node.

The pathways for excitation of the atrioventricular node enter either superiorly, as the so-called 'fast' pathway, or inferiorly as the 'slow' pathway. However, knowledge of the specific anatomical details of these pathways is limited. Most of the experimental studies that established the existence of these pathways were conducted in mammalian hearts, which have subtle differences to human hearts. In this review, the authors summarise their recent experiences investigating human cardiac development, correlating these results with the arrangement of the connections between the atrial myocardium and the compact atrioventricular node as revealed by serial sectioning of adult human hearts. They discuss the contributions made from the atrioventricular canal myocardium, as opposed to the primary ring. Both these rings are incorporated into the atrial vestibules, albeit with the primary ring contributing only to the tricuspid vestibule. The atrial septal cardiomyocytes are relatively late contributors to the nodal inputs. Finally, they relate our findings of human cardiac development to the postnatal arrangement.