We have read the interesting article from Luciani and colleagues [1] documenting the outcomes into the second decade after the Ross procedure in infants and children from the Italian Paediatric Ross Registry. Conclusion concisely stated the Ross procedure was a low risk palliative procedure for aortic valve abnormalities at the expense of valve-related reoperation.

Contrary to prior evidence, autograft reoperation was more common than homograft in their cohort, raising the concern about the autograft failure in paediatric population. Besides the predictors which the authors discussed, the interaction between the left ventricle (LV) and the autograft is an essential associated factor.

Raedle-Hurst and associates [2] reported that elevation of LV volumes, both systolic and diastolic, could still be noticed in patients years after the Ross operation. Theoretically, the residual LV dilation impairing the autograft annulus geometry, will change steady dynamics and exhaust autograft wall structures. Therefore root dilation and valvular regurgitation will exist more significant, translating into clinical autograft failure.

In 2005, authors of the present study had reported younger age at Ross procedure was predictive of late autograft dilatation [3]. However, there was a potential confounding because patients who have Ross at an early age usually presented with a severe valve abnormality and a severely impaired LV. Interestingly, Hoerer and colleagues [4] reported different findings concerning the autograft complication. In their cohort, the autograft annulus postoperatively tended to enlarge and regurgitation develops predominantly in older children. A corollary to this observation is that older patients have a more impaired LV which suffers from the haemodynamic abnormality for a longer time.

These two findings seem to be ostensibly different, however, have one common nature: the impaired LV, substantially highlighting the role of LV in the development of autograft failure. All these evidence suggest LV may be a potential key to reduce autograft complications. Hence there are more information could be further illustrated by this study as the largest multi-center paediatric cohort, including the baseline LV diameter and function of the study population, the recovery of the impaired LV and their potential relationship. Moreover, additional comments about this issue would be helpful.

References

[1] Luciani GB, Lucchese G, Carotti A, et al. Two decades of experience with the Ross operation in neonates, infants and children from the Italian Paediatric Ross Registry. Heart 2014 0:heartjnl-2014-305873v1- heartjnl-2014-305873; doi:10.1136/heartjnl-2014-305873

[2] Raedle-Hurst TM, Hosse M, Hoffmann S, et al. Ventricular performance assessed by 2-dimensional strain analysis after Ross operation versus aortic valve reconstruction. Ann Thorac Surg 2013;96:1567-73.

[3] Luciani GB, Favaro A, Casali G, et al. Ross operation in the young: a ten-year experience. Ann Thorac Surg 2005;80:2271-7.

[4] Horer J, Kasnar-Samprec J, Charitos E, et al. Patient age at the Ross operation in children influences aortic root dimensions and aortic regurgitation. World J Pediatr Congenit Heart Surg 2013;4:245-52.

Conflict of Interest:

None declared

We read with great interest the article by Ismail et al, (1) looking at the role of late gadolinium enhancement (LGE) cardiac magnetic resonance in the risk stratification of patients with hypertrophic cardiomyopathy (HCM). We would like to congratulate the authors for delineating the interesting findings that the amount of myocardial fibrosis was a strong univariable predictor of sudden cardiac death (SCD) albeit the effect was not maintained after adjusting for LV-EF.

Interestingly, in this study of consecutive referrals of patients with suspected/known HCM to a single large tertiary centre, 18% of the patient cohort had apical HCM phenotype. Traditionally, apical HCM has been considered a rarer variant of HCM, with a prevalence of approximately 7% in previous studies, with known more benign prognosis and lower risk of SCD (2).

Anecdotally, in our large tertiary CMR Unit we see a similar 18% of apical HCM phenotype in patients with suspected/known HCM (as in the current study), suggesting the disease variant is perhaps not as rare as initially thought. This could be explained by the higher diagnostic value of CMR vs echo in detecting apical HCM. (3)

It would be very interesting to clarify to which extent the findings of this study can be fully applicable to patients with apical HCM. It is not uncommon to find a significant amount of late gadolinium myocardial enhancement (replacement fibrosis) in the hypertrophied apical segments. Does this carry the same risk as demonstrated in Ismail et al.(1), in a cohort with intrinsic more benign prognosis? Would this yet be another reason in favor of considering apical HCM as a separate entity? (4)

Acknowledgements

NIHR Bristol Biomedical Research Unit in Cardiovascular Medicine.

The views expressed are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research, or Department of Health.

References

1. Ismail TF, Jabbour A, Gulati A, Mallorie A, Raza S, Cowling TE, et al. Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy. Heart [Internet]. 2014 Jun 24 [cited 2014 Aug 12];heartjnl-2013-305471-. Available from: http://heart.bmj.com/content/early/2014/06/24/heartjnl- 2013-305471.full?hwshib2=authn%3A1407961738%3A20140812%253Aae52e5ce-0f8e- 43c3-a6eb-c194a4650ad2%3A0%3A0%3A0%3AF2LsLqYFBrKXczCM8MPT0g%3D%3D

2. Eriksson MJ, Sonnenberg B, Woo A, Rakowski P, Parker TG, Wigle ED, et al. Long-term outcome in patients with apical hypertrophic cardiomyopathy. J Am Coll Cardiol [Internet]. Journal of the American College of Cardiology; 2002 Feb 20 [cited 2014 Aug 12];39(4):638-45. Available from: http://content.onlinejacc.org/article.aspx?articleid=1127753

3. Moon JCC, Fisher NG, McKenna WJ, Pennell DJ. Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography. Heart [Internet]. 2004 Jun [cited 2014 Aug 18];90(6):645-9. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1768283&tool=pmcentrez&rendertype=abstract

4. Maron BJ, Haas TS, Kitner C, Lesser JR. Onset of apical hypertrophic cardiomyopathy in adulthood. Am J Cardiol [Internet]. 2011 Dec 15 [cited 2014 Aug 13];108(12):1783-7. Available from: http://www.sciencedirect.com/science/article/pii/S0002914911024301

Conflict of Interest:

None declared

We are intrigued by the article by Priest et al. The importance of genomics has been clearly identified and the article beautifully describes the role of genetics in cardiovascular medicine but concentrates on inherited arrthymias, cardiomyopathies and occasional pharmacogenomics profiling. We suggest they have failed to consider the large, unrecognized need for genomics in adults patients with congenital heart conditions.

More than 90% of patients with congenital heart conditions now survive to adulthood and yet as neonates/children there was restricted availability of genetic testing and limited techniques. When such patients attend the adult clinic they want to know the inheritance risk of their condition. Yet there is an additional potential to, risk stratify other family members for syndromic as well as isolated congenital cardiac defects. Multiple studies have shown that that congenital cardiac defects demonstrate family clustering which then have a higher incidence of inheritance 1 The genomic wide association study (GWAS) was the first to identify the locus for the common congenital heart condition of atrial septal defect (the locus demonstrated to be a defect at chromosome 4p16)2. We know ASD???s run in families but in addition there is a familial ASD sub group who are at risk for late complete heart block. Such ???personalized??? medicine, guided by genomics, help discriminate which family members to screen and who to keep under long term follow up. For example, the presence of left ventricular outflow tract obstruction in an index case may help to identify bicuspid aortic valve in 1st degree family members which has important long-term clinical implications for morbidity and mortality

The current paediatric guidelines (AHA) suggest gene testing for infants born with interrupted aortic arch type B, truncus arteriosus, aortic arch anomalies, ToF with absent pulmonary valve and other conotruncal anomalies3. There is an absence of guidance in respect of gene testing in the adult patient and yet simply testing for 22q11 deletion in ALL conotruncal abnormalities finds a proportion (5.8%) who have the deletion (despite no phenotypic features) ??? clearly important given the 50% inheritance risk 4.

We have been able to offer congenital heart disease patients medical and surgical services to improve their quality of life leading to survival beyond adulthood but limited focus on genetics. There may be more to offer ??? for example, the genes that cause Noonan-related disorders are those that affect the RAS pathway to increase growth ??? i.e. they are potentially tumour-predisposing genes. These individuals are at risk of neoplasia.

Congenital (paediatric) cardiologists are good at recognizing and gene testing ???syndromic??? patients, but there remain patients seen in the adult clinics who were never tested as children. Furthermore, ???non syndromic??? patients with congenital heart conditions, may have recognizable features (phenotype or association of conditions) to a geneticist who would then suggest an appropriate gene panel. We urge the close collaboration of the congenital cardiologist and geneticist in the adult congenital heart clinic. and geneticist to guide not only inheritance risk, but cascade screening and perhaps predict future risks. ???Genomics in the adult congenital heart practice. Indeed!

Reference:

1. Burn J, Brennan P, Little J, Holloway S, Coffey R, et al. Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study. Lancet. 1998; 351:311???316.

2. Heather J. Cordell, Jamie Bentham, Ana Topf et al ???Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16??? Nat Genet. Jul 2013; 45(7): 822???824

3. Pierpont ME1, Basson CT, Benson DW Jr et al ???Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics??? Circulation. 2007 Jun 12;115(23):3015-38

4.Beauchesne LM, Warnes CA, Connolly HM, Ammash NM, Grogan M, et al. Prevalence and clinical manifestations of 22q11.2 microdeletion in adults with selected conotruncal anomalies. J Am Coll Cardiol. 2005;45:595???598.

Conflict of Interest:

None declared

We read with interest the recent article on survival by stroke volume index (SVI) in patients with low-gradient (LG) normal ejection fraction (EF) severe aortic stenosis (AS), which demonstrated lower SVI is incrementally associated with mortality [1].

The authors discuss a putative mechanism of low stroke volume secondary to concentric remodeling which results in reduced LV cavity size. This, is turn, impedes LV diastolic filling, culminating in diminished systolic function despite EF. The authors quote evidence of systolic impairment, e.g. reduced longitudinal strain, in similar cohorts with preserved EF [2]. In the current study, the subgroup with lowest SVI, and therefore presumed most severe systolic impairment despite EF >50%, demonstrated the thickest relative wall measurements. We believe this observation helps to explain the apparent paradox between significant myocardial dysfunction and preservation of EF in this cohort and in the wider 'heart failure with preserved ejection fraction' context. Recent mathematical modeling of LV contraction has shown that both myocardial shortening and end-diastolic wall thickness are determinants of EF [3]. Essentially, absolute LV wall thickening, as defined by the absolute difference between wall thickness at end-systole and end-diastole, may be nearly normal in patients with concentric LV hypertophy (LVH) because absolute systolic thickening will be augmented in response to increased end-diastolic LV wall thickness. As a result, the endocardial displacement and EF will also be normal, as the external LV volume remains fairly static throughout the cardiac cycle [4] and the absolute wall thickening may appear to compensate for any contractile strain abnormality. The development of concentric LVH ventricle may be viewed as a compensatory response that normalises contractile stress and total contractile force. However, if contractile stress remains reduced, the contractile force will be inadequate and result in a fall in stroke volume despite the preserved EF. In order to understand the apparent discrepancy in SV and EF, one must distinguish between contractile strain and stress and the relationship between end-diastolic wall thickness and EF.

The authors elected to investigate SV indexed to body surface area. However, it would be interesting to know whether correcting EF for the presence of concentric LVH (EFc), as described in mathematical modeling studies of the LV [3], would be a useful prognostic marker in this cohort of patients. After all, EFc is potentially an even more relevant allometric indexed value given the importance of end-diastolic wall thickness in patients with concentric LVH and systolic impairment but preserved EF.

References:

[1] Eleid MF, Sorajla P, Michelena HI, et al. Survival by stroke volume index in patients with low-gradient normal EF severe aortic stenosis. Heart. Published Online First: 12 September 2014. Doi: 10.1136/heartjnl-2014-306151

[2] Adda J, Mielot C, Giorgi R, et al. Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunction as assessed by speckle-tracking echocardiography: a multicenter study. Circ Cardiovasc Imaging 2012; 5: 27 -35.

[3] Maciver DH. A new method for quantification of left ventricular systolic function using a corrected ejection fraction. Eur J Echocardiogr 2011; 12: 228-34.

[4] Emilsson K, Brudin L, Wandt B. The mode of left ventricular pumping: is there an outer contour change in addition to atrioventricular plane displacement? Clin Physiol 2001; 21: 437-446.

Acknowledgements:

NIHR Bristol Biomedical Research Unit in Cardiovascular Medicine.

The views expressed are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research, or Department of Health.

Conflict of Interest:

None declared