The recent article by Jun and Neal (1), "Low dietary sodium in heart
failure: a need for scientific rigour," calls for greater consistency and
attention in one outcome related to salt intake. The Salt Institute is in
complete agreement with their call for greater scientific rigour and
believes, in the interests of public health, that this should be extended
to all health outcomes related to dietary sodium intake. While...
The recent article by Jun and Neal (1), "Low dietary sodium in heart
failure: a need for scientific rigour," calls for greater consistency and
attention in one outcome related to salt intake. The Salt Institute is in
complete agreement with their call for greater scientific rigour and
believes, in the interests of public health, that this should be extended
to all health outcomes related to dietary sodium intake. While blood
pressure is one of several important surrogate measurements for
cardiovascular disease, it is not a key measure for many other health
outcomes. Overall health outcomes related to essential nutrients are
generally described by their dose response and the J- or U-shaped curve
(Bertrand's Rule) is a common characteristic of virtually all micro-
nutrients, including sodium. Unfortunately, the available data for sodium
is erratic, contradictory and continually open to subjective
interpretation.
It is unfortunate that Jun and Neal neglected to including a
reference to the recent CDC-sponsored IOM Committee on the Consequences of
Sodium Reduction in Populations report (1) which found no evidence for
benefit and some evidence suggesting risk of adverse health outcomes
associated with the sodium intake levels recommended by the Dietary
Guidelines (1,500 to 2,300 mg/day) among those with diabetes, kidney
disease, or CVD. The report further stated that evidence on both the
benefit and harm is not strong enough to indicate that subgroups should be
treated differently than the general U.S. population and that direct
health outcomes do not support recommendations to lower sodium intake
within these subgroups down to or even below 1,500 mg/day. Obviously, the
practice of relying on a single surrogate health measure has limitations
resulting in questionable Dietary Guidelines that have been in effect for
a decade.
Of critical significance, on page 20 (Section 1-2) of this new IOM
report, the Committee on the Consequences of Sodium Reduction in
Populations specificallyquoted a statement from the original Dietary
Reference Intakes stating that the requirements for sodium were not
derived from actual evidence, but were arbitrarily set. "In establishing
DRI values for sodium, the Panel on Dietary Reference Intakes for
Electrolytes and Water (IOM, 2005) found insufficient evidence to derive
Recommended Dietary Allowances. Instead Adequate Intakes (AIs) were set
for all life stage and gender groups." This new report, along with
numerous Cochrane Collaboration and other meta-analyses underscore the
fact that the evidence base is not currently at a level of quality that
can be considered scientifically acceptable. The unrestricted, universal
acceptance of these recommendations, despite their lack of an acceptable
base of scientific evidence, makes it all the more important that greater
rigour be applied, before they can be considered valid.
Morton Satin
Salt Institute
Alexandria, VA
References
1) Min Jun, Bruce Neal, Low dietary sodium in heart failure: a
need for scientific rigour Heart Online First, published on June 1, 2013
as 10.1136/heartjnl-2012-303266.
2) IOM (Institute of Medicine). (2013). Sodium intake in
populations: Assessment of evidence. Washington, DC: The National
Academies Press. Accessed at http://www.iom.edu/Reports/2013/Sodium-Intake
-in-Populations-Assessment-of-Evidence.aspx on 2/6/2013.
Conflict of Interest:
Morton Satin is employed by the Salt Institute, Alexandria, VA 22314, USA
We enjoyed the image challenge published by Wu et al which
illustrates a case of contained left ventricular rupture [1]. 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...
We enjoyed the image challenge published by Wu et al which
illustrates a case of contained left ventricular rupture [1]. 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 [4]. 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'
[2]. 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 [2].
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.
In non-cardiac surgery, the role of beta-blocakde to prevent
perioperative death is extremely controversial. While it is now agreed
that the results from the DECREASE family of trials cannot be trusted (1),
the evidence from the remaining 9 "secure" trials is somewhat difficult to
interpret. The recent meta-analysis by Bouri et al. (1) has concluded
that, according to these 9 trials, beta-blockade significantly increases...
In non-cardiac surgery, the role of beta-blocakde to prevent
perioperative death is extremely controversial. While it is now agreed
that the results from the DECREASE family of trials cannot be trusted (1),
the evidence from the remaining 9 "secure" trials is somewhat difficult to
interpret. The recent meta-analysis by Bouri et al. (1) has concluded
that, according to these 9 trials, beta-blockade significantly increases
mortality (risk ratio=1.27; 95% confidence interval: 1.01 to 1.60;
p=0.04), but this result was at the limits of statistical significance.
Since trial-sequential analysis (TSA) can contribute to better
interpret controversial findings from meta-analyses (2-4), we employed
this statistical technique to re-examine the results from the 9 secure
trials. The end-point was mortality. We assumed two-sided testing, type-
1 error=5%, power=80%, event frequency for controls=2.5% (i.e. the
arithmetic cumulative event rate in the 9 control groups), and relative
risk reduction (RRR)=25%. Boundaries for superiority, inferiority or
futility were calculated according to the O'Brien-Fleming alpha-spending
function. The graph of TSA was plotted according to a specific software
(User Manual for TSA, Copenhagen Trial Unit 2011).
Figure 1 summarises our analysis (9 trials; 10,529 patients). Our
results essentially confirm the conclusion by Bouri et al. (1). On the one
hand, our trial-sequential graph showed that 17,495 patients would be the
optimal sample size to show a relative difference of +/-25%. On the other
hand, the z-curve based on the 9 trials reached an area very close to the
boundary of inferiority. Although this boundary was not crossed, the
pattern of the curve indicated that these results demonstrate at least
futility (i.e. proof of no effectiveness), while they also tend to
approach the demonstration of inferiority.
On the basis of this TSA, the use of beta-blockade in non-cardiac
surgery is statistically proven to be ineffective (futility) and,
additionally, is very likely to be harmful. Since futility of this
pharmacological intervention is statistically demonstrated, in our view no
further trials should be carried out to study the potential benefit in
these patients; furthermore, in consideration that a preliminary evidence
supports the hypothesis of a harmful effect, this is another reason why
beta-blockade in non-cardiac surgery should be abandoned also in clinical
practice.
References
1. Bouri S, Shun-Shin MJ, Cole GD, Mayet J, Francis DP. Meta-analysis
of secure randomised controlled trials of ?-blockade to prevent
perioperative death in non-cardiac surgery. Heart. 2013 Jul 31. doi:
10.1136/heartjnl-2013-304262.
2. Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential
analysis may establish when firm evidence is reached in cumulative meta-
analysis. J ClinEpidemiol. 2008 Jan;61(1):64-75.
3. Messori A, Fadda V, Maratea D, Trippoli S. ?-3 Fatty Acid
Supplements for Secondary Prevention of Cardiovascular Disease: From "No
Proof of Effectiveness" to "Proof of No Effectiveness". JAMA Intern Med.
2013 Jun 17:1-2.
4. Messori A, Fadda V, Maratea D, Trippoli S. Erythropoiesis-
stimulating agents in heart failure: no proof of effectiveness or proof of
no effectiveness? Eur J Heart Fail. 2013 Aug;15(8):944-5.
Figure 1. Trial sequential analysis of 9 "secure" randomized trials.
In the z-curve (represented in blue), individual trials correspond to
individual segments; trials are plotted in chronological order (from left
to right). The x-axis indicates the cumulative number of patients; the
starting point of the z-curve is at x=0, i.e. inclusion of no trials.
Abbreviations and symbols: red lines are the boundaries for superiority or
inferiority while green lines are the boundaries for futility;
T=treatment; C=controls.
Availability: this Figure can be downloaded from
the following Internet address:
http://www.osservatorioinnovazione.net/supplements/messori-eletter-heart-
2013.pdf
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...
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
We thank Dr Cohn for pointing out that our description[1] of the
POISE dosage described only the first dose. The general maintenance dose
was 200 mg extended release once a day (equivalent to 50 mg immediate
release three times a day). If systolic pressure dropped below 100 mmHg,
or heart rate below 50 bpm, beta-blockade was paused and later restarted
at 100 mg od.
We thank Dr Cohn for pointing out that our description[1] of the
POISE dosage described only the first dose. The general maintenance dose
was 200 mg extended release once a day (equivalent to 50 mg immediate
release three times a day). If systolic pressure dropped below 100 mmHg,
or heart rate below 50 bpm, beta-blockade was paused and later restarted
at 100 mg od.
Moreover, as Dr Cohn points out, the metoprolol was given twice. The
first was 2 - 4 hours before surgery. The surgery then lasted a variable
time. During the first 6 hours of recovery, if the heart rate was above 80
bpm and the blood pressure above 100 mmHg, the second dose was given. If
the blood pressure was above 100 mg but the heart rate only between 50 and
80, the second dose was given only at the end of the 6 hours.
No patients received the protocol permitted theoretical dosage of 400
mg in the initial 24 hours[2].
Causation
We can see Dr Cohns' point that causation can never really be proved
in medicine. The statistically significant increased mortality was merely
the result of the randomised controlled trial data.
Dr Cohns' Conclusions
We thank Dr Cohn for encapsulating more elegantly than we managed
ourselves, the conclusions of our paper.
References
1. Bouri S et al. Meta-analysis of secure randomised controlled
trials of ?-blockade to prevent perioperative death in non-cardiac
surgery. Heart 2013. doi: 10.1136/heartjnl-2013-304262.
2. Poldermans D, Devereaux P J. The experts debate:Perioperative beta
-blockade for noncardiac surgery - proven safe or not? CCJM 2009;76: S84-
92]
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.
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.
We read with interest the study by Providencia et al. which
demonstrated that dabigatran had a similar efficacy and safety profile as
warfarin in the setting of catheter ablation (CA) of atrial fibrillation
(AF) (1). These findings concur with two other meta-analyses on the same
topic (including one from our group) which have been recently published
(2,3). All the published meta-analyses on this...
We read with interest the study by Providencia et al. which
demonstrated that dabigatran had a similar efficacy and safety profile as
warfarin in the setting of catheter ablation (CA) of atrial fibrillation
(AF) (1). These findings concur with two other meta-analyses on the same
topic (including one from our group) which have been recently published
(2,3). All the published meta-analyses on this topic were limited by the
hierarchy of evidence, which was mostly derived from observational
studies. These observations warrant validation by a randomized controlled
trial. However, patients will probably undergo the procedure while on
dabigatran based on the current available evidence until a controlled
study is carried out. How to manage the drug peri-procedurally and
minimize the risks of bleeding and thromboembolism are importance points
to be considered. A reasonable approach based on the importance of
limiting interruption to peri-procedural anticoagulation and considering
the pharmacokinetics of dabigatran is to hold 1-2 doses of dabigatran and
resume the medication a shortly after achieving post-procedural hemostasis
at the vascular access site. Indeed, in our analysis limited to studies
that held 1-2 doses of dabigatran and resumed the drug on the same day as
the procedure, we not only found no significant difference in bleeding or
thromboembolic events between interrupted dabigatran and uninterrupted
warfarin, but importantly there was zero to mild in between studies
heteterogenity. Also, it is reasonable to consider transesophageal
echocardiography (TEE) before CA of AF in patients on dabigatran given the
relatively lesser experience with the drug and the fact that most reported
studies have used TEE before the ablation procedure.
References:
1.Providencia, R., Albenque, J-P., Combes, S.,et al. Heart Published
Online First: 2013 Jul 22 doi:10.1136/ heartjnl-2013-304386
2.Bin Abdulhak, A., Khan, AR. ,Tleyjeh,I.,et al.Safety and efficacy
of interrupted dabigatran for peri-procedural anticoagulation in catheter
ablation of atrial fibrillation: a systematic review and meta-
analysis.Europace. 2013 August 16 doi: 10.1093/europace/eut239
3.Hohnloser, S., Camm, A. Safety and efficacy of dabigatranetexilate
during catheter ablation of atrial fibrillation: a meta-analysis of the
literature.Europace. 2013 August 16 doi:10.1093/europace/eut241
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 e...
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
Dear Editor,
We read with great interest the recent meta-analysis showing that low-dose
caffeine may have a protective effect on risk of atrial fibrillation,
while no favorable effect was found for high dose of caffeine, and a
sketch of a J-shape curve was speculated on the association of caffeine
with risk of atrial fibrillation.1 Therefore, to clarify the dose-response
relationship on caffeine and risk of atrial fibrilla...
Dear Editor,
We read with great interest the recent meta-analysis showing that low-dose
caffeine may have a protective effect on risk of atrial fibrillation,
while no favorable effect was found for high dose of caffeine, and a
sketch of a J-shape curve was speculated on the association of caffeine
with risk of atrial fibrillation.1 Therefore, to clarify the dose-response
relationship on caffeine and risk of atrial fibrillation, the restricted
cubic spline model and multivariate random-effect meta-regression2 was
performed, which was described in detail in our previous paper. 3-4 In
brief, a restricted cubic spline model with three knots at the 25, 50, and
75th percentiles of the caffeine levels, was estimated using generalized
least square regression taking into account the correlation within each
set of published relative risk (RR). Then the study-specific estimates
were combined using restricted maximum likelihood method in a multivariate
random-effects meta-analysis. A P value for nonlinearity was calculated by
testing the null hypothesis that the coefficient of the second spline is
equal to 0.
Among the seven observational studies included in the meta-analysis,1
three reported the association of caffeine with atrial fibrillation (the
reference numbers are 35-37), while the other four reported association of
coffee with atrial fibrillation (the reference numbers are 31-34).
Therefore, data from the three prospective cohort studies on caffeine and
atrial fibrillation were used in this dose-response analysis, including
1,796 atrial fibrillation cases and 91,290 participants. A linear dose-
response relationship of caffeine with risk of atrial fibrillation was
found (P for non-linearity=0.86), and the risk of atrial fibrillation
decreased by 2% [RR (95 CI %) =0.98 (0.94-1.01), P=0.21] for every 200
mg/day increment of caffeine consumption. The RR (95 CI%) of atrial
fibrillation was 0.99 (0.95-1.02), 0.97 (0.91-1.04), 0.96 (0.87-1.06),
0.95 (0.85-1.07), 0.94 (0.84-1.04), 0.93 (0.83-1.04), 0.93 (0.82-1.04),
0.92 (0.80-1.05), 0.91 (0.77-1.07) and 0.90 (0.75-1.09) for 100, 200, 300,
400, 500, 600, 700, 800, 900 and 1000 mg/day of caffeine intake,
respectively. In our opinion, readers should have a better understanding
regarding the important results by Caldeira et al.,1 taking into account
the aforementioned findings.
References
1 Caldeira D, Martins C, Alves LB, et al. Caffeine does not increase the
risk of atrial fibrillation: a systematic review and meta-analysis of
observational studies. Heart 2013;99:1383-1389.
2 Orsini N, Li R, Wolk A, et al. Meta-analysis for linear and nonlinear
dose-response relations: examples, an evaluation of approximations, and
software. Am J Epidemiol 2012;175:66-73.
3 Jiang W, Wu Y, Jiang X. Coffee and caffeine intake and breast cancer
risk: an updated dose-response meta-analysis of 37 published studies.
Gynecol Oncol 2013;129:620-629.
4 Wang Y, Yu X, Wu Y, et al. Coffee and tea consumption and risk of lung
cancer: a dose-response analysis of observational studies. Lung Cancer
2012;78:169-170.
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....
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.
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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....
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