Displaying 1-10 letters out of 659 published
Clinical Genomics and the adult with congenital heart disease: new opportunities"
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!
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:
Re:Pre-procedural fasting for coronary interventions: is it time to change practice?
We read with interest the comments from Wijeyeratne et al (1) regarding our paper. They commend our study (2) for questioning the need for fasting prior to percutaneous cardiac procedures and highlight the lack of evidence either for or against the necessity to fast in this scenario. We agree with their comments and fully accept the limitations of our retrospectively analysed data. While we don???t expect our paper to result in an immediate major practice shift in cardiology, we certainly hope that it will raise awareness of this issue.
As they point out, patients might be instructed to fast, drink fluids only or not fast at all (for varying periods of time) prior to the exactly the same procedure performed in different institutions. There are no guidelines and only scant evidence to guide practice. One can see how this inconsistency in practice has arisen.
There are understandable concerns that if patients are not fasted, then their risk of complications may increase. However, these concerns are probably overstated and indeed, it is possible that harm may be more likely to occur in fasted patients.
We agree that concerns regarding a possible increased risk of pulmonary aspiration in non-fasted patients are probably unfounded. Patients who undergo primary percutaneous coronary intervention (PPCI) for acute ST elevation MI (STEMI) are not fasted and there is no reported excess of peri-procedural pulmonary aspiration on the British Cardiovascular Intervention Society (BCIS) national registry. An open label study by Kwon et al (3) reported that no patient (fasted vs non- fasted) undergoing cerebral angiography had pulmonary aspiration. A prospective study by Agrawal et al (4) demonstrated that there was no association between adverse events and not being fasted in children undergoing pre-procedural sedation in emergency department.
When patients are not fasted, we suspect radial access is easier and there appears to be less sedation-induced blood pressure drop. We believe that allowing patients to freely eat and drink before their scheduled procedure makes them less anxious as described by some patients: ???They are having a procedure, not an operation???. In centres that routinely fast their patients, delays may occur if a patient hadn???t fasted for long enough before their scheduled procedure time or if they had inadvertently broken their fast. This may prolong inpatient stay and increase costs.
We concur that more studies are required and our group is currently designing a larger, multi-center prospective study aiming to compare the two practices (fasting versus non-fasting prior to percutaneous cardiac procedures). We suspect that our findings from that larger study will provide further evidence that pre-procedural fasting is not required.
KEYWORDS: Interventional Cardiology; Quality of Care and Outcomes, Pre Procedural fasting.
1. Wijeyeratne YD, Wendler R, Spray D, Bunce N;Preprocedural fasting for coronary interventions: is it time to change practice?Heart 2014;100:13
2. Hamid T, Aleem Q, Lau Y, Singh R, McDonald J, Macdonald JE, Sastry S, Arya S, Bainbridge A, Mudawi T, Balachandran K. re-procedural fasting for coronary interventions: is it time to change practice? Heart. 2014 Apr;100(8):658-661
3. Kwon OK, Oh CW, Park H, Bang JS, BaeHJ, Han MK, Park SH, Han MH, Kang HS, Park SK, Whang G, Kim BC, Jin SC; Is fasting necessary for elective cerebral angiography? AJNR Am J Neuroradiol. 2011 May;32(5):908- 910
4. Agrawal, D., Manzi, S.F., Gupta, R. et al. Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department. Ann Emerg Med. 2003; 42: 636-646
Conflict of Interest:
Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy (HCM) - but what about 'apical' HCM?
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)
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.
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:
Correspondence: sudden death is associated both with epilepsy and with use of antiepileptic medications
We read with interest the recent paper by Bardai et al1(1), which reports that epilepsy and antiepileptic drugs (AEDs) were independently associated with sudden cardiac death (SCD). We are unconvinced that such a clear distinction between disease and drug effects can be made in this study as all people with epilepsy were by definition taking AEDs. We believe this is why SCD risk in those with epilepsy (Table 2) and in AED users with epilepsy (Table 3) was the same: OR 2.8 (95% CI: 1.4, 5.3). It is unclear whether these numbers reflect disease effects, drug effects, or both. It is reported that people with epilepsy are at increased risk of SCD, yet in this population there is a major diagnostic alternative: sudden unexpected death in epilepsy, an autopsy-negative mostly seizure-related type of sudden death with cardiac and non-cardiac causes.(2) We do not believe that sudden death in people with epilepsy can be assumed to be of cardiac origin (versus, for example, neurogenic respiratory depression) without documentation of a cardiac mechanism of death (e.g. by ECG). Carbamazepine and gabapentin were the only individual AEDs associated with increased SCD risk. The authors attribute this to the supposed sodium channel blocking properties of these drugs, but we believe that indication bias cannot be excluded. Carbamazepine is the drug of choice in people with focal seizures and stroke is a leading cause of this type of epilepsy, particularly in the elderly.(3) An important indication for gapabentin is diabetic chronic neuropathic pain.(4) It is possible that a worse cardiovascular status rather than sodium channel blocking properties explains the higher SCD risk in users of these AEDs. Despite the use of a large database, many numbers are small, so the demonstrated significant effect for sodium channel blocking AEDs but not for non-sodium channel blocking AEDs may reflect limited sample size rather than differences in effect. There was a consistent trend; all reported AED ORs were greater than the null value. This paper is important in that it confirms that epilepsy in the community is associated with an increased risk of sudden natural death. Future studies with additional documentation of death mechanisms, correction for indication bias and larger sample size are needed to explain the cause of this excess risk and clarify the role of AEDs.
1. Bardai A, Blom MT, van Noord C, et al. Sudden cardiac death is associated both with epilepsy and with use of antiepileptic drugs. Heart. 2014 Jul 16. doi: 10.1136/heartjnl-2014-305664. 2. Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet 2011; 378(9808):2028-2038. 3. Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of seizures in stroke patients. Neurology 2006;67(12 Suppl 4):S3-9. 4. Moore RA, Wiffen PJ, Derry S, et al. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014 Apr 27. doi: 10.1002/14651858.CD007938.pub3
Conflict of Interest:
The role of Left Ventricle in the Autograft Complication after ROSS operation
We have read the interesting article from Luciani and colleagues  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  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 . 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  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.
 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
 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.
 Luciani GB, Favaro A, Casali G, et al. Ross operation in the young: a ten-year experience. Ann Thorac Surg 2005;80:2271-7.
 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:
Epistenocardiac pericarditis can be an electrocardiographic challenge!
We enjoyed the image challenge published by Wu et al which illustrates a case of contained left ventricular rupture . In the explanation, authors have excluded pericarditis based on the absence of fever and characteristic pericarditis ECG findings. We would like to emphasize that early post-infarction pericarditis ("epistenocardiac") is notorious to cause atypical ECG changes which are often territorial to the infarct area [2-5]. One of our previous studies demonstrated that only 3.2% patients with epistenocardiac pericarditis present with classical Stage-I pericarditic ECG changes . Pericarditis in the presented case should be correctly ruled out by the absence of a pericardial rub and the presence of significant reciprocal ST-depressions in III and aVF on the third ECG-tracing. Authors also point out that the key to the diagnosis for left ventricular free wall rupture (LVFWR) is the presence of pericardial effusion. In our opinion, the absence of pericardial effusion has a very high negative predictive value for LVFWR, however the presence of it (even hemorrhagic effusion) does not confirm the diagnosis as an effusion may often accompany an 'effusive epistenocardiac pericarditis' . The hallmark to the echocardiographic diagnosis of LVFWR is the actual visualization of wall-rupture and/or the classical color-doppler findings with or without the use of an echo contrast .
References: 1.Wu H, Qian J, Ge J. Recurrent ST-segment elevation in infarct-associated leads. Heart. 2014 Jul 29. pii: heartjnl-2014-306289. doi: 10.1136/heartjnl-2014-306289. (PMID: 25073887). 2.Spodick DH: The Pericardium: A Comprehensive Textbook, Marcel Dekker, New York 1997. pp: 334-367. 3.Bruce MA, Spodick DH. Atypical electrocardiogram in acute pericarditis: characteristics and prevalence. J Electrocardiol. 1980;13(1):61-66. 4.Krainin FM, Flessas AP, Spodick DH. Infarction-associated pericarditis. Rarity of diagnostic electrocardiogram. N Engl J Med. 1984;311(19):1211- 1214. 5.Chhabra L, Chaubey VK, Spodick DH. Recurrent myocardial infarction or Epistenocardiac pericarditis: how can surface ECG be useful in clinical decision making? Hellenic J Cardiol. 2014. In Press.
Conflict of Interest:
Effect of incomplete revascularization
In the above paper, there is no mention of the influence of incomplete revascularization on the results. This is an important variable that should be taken into account to show whether an independant effect of lesion calcification on outcomes exists.
Conflict of Interest:
Higher relative wall thickness in strength athletes using anabolic steroids
In the study presented from Utomi et al (1), the Morganroth hypothesis concerning a different left ventricular (LV) adaptation between endurance and strength athletes has been tested. The authors demonstrated a normal LV geometry in male strength athletes and concluded that the hypothesis of a LV concentric hypertrophy should be revised. We would like to point out that we have questioned the disproportionate increase in LV wall thickness in strength athletes, resulting in a concentric hypertrophy, already in 1989 (2) and 1999 (3). We have demonstrated that pure resistance-trained athletes (weightlifters and bodybuilders) and combined resistance- and endurance-trained athletes (rowers) do not develop a LV concentric hypertrophy in the absence of pathological pressure loads or hypertrophic cardiomyopathy. Only strength athletes misusing anabolic steroids exhibited distinctly higher relative wall thicknesses compared to all other athletes (3). Unfortunately, in the publication of Utomi et al (1), the influence of anabolic steroids on the ratio between LV myocardial thickness and internal diameter is not discussed. Similarly, in most previous studies reporting on a concentric hypertrophy in strength athletes, a drug history, especially the misuse of anabolic steroids, is missing. Therefore, in apparently healthy athletes, exhibiting a disproportionate increase in wall thickness, misuse of anabolic steroids has to be considered. In addition, endurance exercise capacity, which is related to the athlete's heart size (4), should be tested (e.g. by VO2max) in such studies to validate the presumed fitness of the studied subjects.
References 1. Utomi V, Oxborough D, Ashley E, et al. Predominance of normal left ventricular geometry in the male "athlete's heart". Heart Published Online First: June 10, 2014. doi: 10.1136/heartjnl-2014-305904. 2. Urhausen A, Holpes R, Kindermann W. One-and two-dimensional echocardiography in bodybuilders using anabolic steroids. Eur J Appl Physiol 1989; 58:633-40. 3. Urhausen A, Kindermann W. Sport-specific adaptations and differentiation of the athlete's heart. Sports Med 1999; 28:237-44. 4. Scharhag J, Schneider G, Urhausen A, Rochette V, Kramann B, Kindermann W. Athlete's heart: right and left ventricular mass and function in male endurance athletes and untrained individuals determined by magnetic resonance imaging. J Am Coll Cardiol 2002;40:1856-1863.
Conflict of Interest:
Definition of peripheral arterial disease in South Asians
Majority of the studies have defined peripheral arterial disease as ankle brachial index (which is a ratio of absolute systolic ankle blood pressures and absolute systolic brachial blood pressures) of <0.9. Peripheral arterial disease ought to be defined by both low ankle brachial index and high ankle brachial index as both low and high ankle brachial index are predictors of cardiovascular disease and mortality in Europeans. The prevalence of hypertension and its association with cardiovascular disease in South Asians do not significantly differ from that of Europeans. The prevalence of ankle brachial index <0.9 in South-Asians is less than in Europeans both in subjects with or without diabetes. However, absolute systolic ankle blood pressures increase with diabetes in young South Asians and these increases are greater in South-Asians compared to Europeans (Kain K, Heart 2013; 99:614-619). Therefore, in South Asians peripheral arterial disease ought to be defined by high ankle brachial index rather than low ankle brachial index and the paradox of lower prevalence of peripheral arterial disease even though South Asians have increased prevalence of ischemic heart disease and ischemic stroke will disappear.
Conflict of Interest:
A lot more work to do to improve Antipodean healthcare
The researchers here used a specified two-week period and their outcome measures were not 'prospective' but effectively cross-sectional. The papers labels itself a 'prospective audit' which makes the fundamental error clinicians often make in confusing a 'de novo consecutive series' of patients with the epidemiologist's definition of a 'prospective' study which is of course a 'cohort study', one in which outcomes are collected later in time.
Furthermore, secondary prevention and cardiac rehabilitation are not 'snapshot' care pathways. Much of the real work begins after discharge - the phone call to the patient at 48 hours, the invite to the post-ACS clinic a few weeks later, and then weeks to months of intensive input through a cardiac rehabilitation programme. This paper does not capture that.
Finally, the findings here that only 46% of ACS (acute coronary syndrome) patients were referred to cardiac rehabilitation are also much worse than European figures from the recent British Association for Cardiovascular Prevention and Rehabilitation (BACPR) audit where referral rates were very near the CVD Outcomes Strategy for England ambition of 65% uptake, (1) whilst according to the last annual report from the Swedish national ACS registry, 79% of all patients aged 75 years or younger attended the secondary prevention first visit (6-8 weeks after the event) and 73% attended the second visit (12-14 months after the event).(2) They are thus wrong to suggest that their results are similar to other international studies - comparing to other ACS registries is not relevant, they need to compare their results to other audits of cardiac rehabilitation.
International comparisons of care does inform new research and policy initiatives that improve the quality of health systems, and this paper merely suggests that Australia and New Zealand are a long way behind Europe.
1. Doherty P, and Lewin, B. The National Audit of Cardiac Rehabilitation: Annual Statistical Report 2013.
2. SWEDEHEART Annual report http://www.ucr.uu.se/swedeheart/index.php/arsrapporter 2012.
Conflict of Interest:
This recent issue is free to all users to allow everyone the opportunity to see the full scope and typical content of Heart.
View free sample issue >>
Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.