We thank the Authors for the careful analysis of our work and the
kind comments. In general, a distinction needs to be made when analysing
clinical outcome after the Ross procedure in paediatric age. Whereas the
neonatal and infant population generally presents with either isolated
(often recurrent) or complex, multilevel LVOTO, which may be associated
with mitral valve disease and varying degrees of LV hypoplasia, the...
We thank the Authors for the careful analysis of our work and the
kind comments. In general, a distinction needs to be made when analysing
clinical outcome after the Ross procedure in paediatric age. Whereas the
neonatal and infant population generally presents with either isolated
(often recurrent) or complex, multilevel LVOTO, which may be associated
with mitral valve disease and varying degrees of LV hypoplasia, the
preschool and school age population generally requires the Ross procedure
for isolated (congenital) aortic valve disease. Therefore, the former
patient subgroup is characterized by high operative risk and reoperations
on the left heart mostly due to technical (autograft) or concomitant
(mitral, aortic arch) problems. On the contrary, in the latter group,
hospital risk is negligible (less than 1%) and reintervention is generally
caused by progressive autograft root dilation and/or dysfunction. In other
words, the pre-school and school age child having the Ross procedure tends
to behave similar to the grown-up or adult, as previously shown by
Hazekamp and associates [1]. Practically, the concern raised by Li and
colleagues applies only to older children. Indeed, in one of our previous
works [2], as well as in the study by Horer and associates [3], attention
was mostly focused on the older child and the young adult, as the infant
population was modestly represented. Thus, differences in baseline
demography (particularly mean age) might perhaps explain, at least in
part, the apparent contradictory results of the multivariate analysis
amongst different studies. In fact, we essentially agree with the point
raised by the Authors, as in the older child and the grown-up presenting
with aortic insufficiency, LV and anular dilation, recurrence or non
regression of LV dilation after the Ross procedure may promote late
autograft dilation and dysfunction. We regret not to be able to further
support this hypothesis in the Italian Paediatric Ross Registry database
[4] due to incompleteness of echocardiographic follow-up information.
References:
1. Hazekamp MG, Grotenhuis HB, Schoof PH, et al. Results of the Ross
operation in a pediatric population. Eur J Cardiothorac Surg. 2005
Jun;27(6):975-9.
2. Luciani GB, Favaro A, Casali G, et al. Ross operation in the
young: a ten-year experience. Ann Thorac Surg 2005;80:2271-7.
3. 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.
4. 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
Unfortunately, data with regards the presence of incomplete
revascularization was available only in the Syntax study and thus this
variable was not inserted in the multivariate model. Besides the aim of
this analysis was to assess for clinical and anatomical variables that are
available before percutaneous coronary intervention and are independent
predictors of worse outcomes, since these variables can be used to
stratif...
Unfortunately, data with regards the presence of incomplete
revascularization was available only in the Syntax study and thus this
variable was not inserted in the multivariate model. Besides the aim of
this analysis was to assess for clinical and anatomical variables that are
available before percutaneous coronary intervention and are independent
predictors of worse outcomes, since these variables can be used to
stratify risk pre-procedure, and thus guide treatment.
Am I missing something here? It is generally accepted that the
omission of a single dose of dabigatran, which has a short elimination
half-life, may place a patient at risk of thromboembolism. So why should
atrial fibrillation ablation be any different especially when one is
potentially stimulating thrombus formation in the left atrium during and
possibly after the procedure? Why not continue the drug through the
proced...
Am I missing something here? It is generally accepted that the
omission of a single dose of dabigatran, which has a short elimination
half-life, may place a patient at risk of thromboembolism. So why should
atrial fibrillation ablation be any different especially when one is
potentially stimulating thrombus formation in the left atrium during and
possibly after the procedure? Why not continue the drug through the
procedure as reported by Maddox et al (1)? Is it not completely illogical
to do otherwise? More trials of this approach are needed. Abdulhak's meta-
analysis (his reference 2) did not include any studies of uninterrupted
dabigatran treatment.
Reference
1.Maddox W, Kay GN, Yamada T et al. Dabigatran versus warfarin for
uninterrupted oral anticoagulation during atrial fibrillation ablation.
Journal of Cardiac Electrophysiology 2013;24:861-865
Peri-ablation dabigatran in atrial fibrillation: not only about
thromboembolism.
We have read with interest the letter by Ward (1) about our recent
publication (2). The author raised an important point: why should
dabigatran be interrupted during a procedure known to be associated with
risk of thromboembolic events? Ward also noted that our meta-analysis did
not include any study with uninterrupted dabigatran....
Peri-ablation dabigatran in atrial fibrillation: not only about
thromboembolism.
We have read with interest the letter by Ward (1) about our recent
publication (2). The author raised an important point: why should
dabigatran be interrupted during a procedure known to be associated with
risk of thromboembolic events? Ward also noted that our meta-analysis did
not include any study with uninterrupted dabigatran. While it is true that
left atrial ablation procedures are associated with risk of
thromboembolism, they also carry risk of potentially life threatening
bleeding.
Given the low thromboembolism and bleeding rates with uninterrupted
warfarin, it would appear reasonable to consider the use of uninterrupted
dabigatran. Factors that have deterred its use include lack of an antidote
and the overall lesser clinical experience with the medication in
comparison to warfarin. An increased requirement for intra-procedural
heparin with peri-ablation dabigatran (3), and prior report of more
bleeding with peri-ablation dabigatran (4) use may have also limited use
of this approach.
Importantly, most of the available studies have examined interrupted
dabigatran versus warfarin (often uninterrupted), and the results of
several meta-analyses (5,6,7) have shown a comparable efficacy and safety
profile for the two anticoagulants. We limited our analysis to studies
that compared interrupted dabigatran with warfarin therapy to minimize in
between studies heterogeneity that would impact interpretation and
applicability the results. If more data become available on uninterrupted
dabigatran use, it could become a more widely accepted approach if safety
is proven.
References:
1. Ward D. Have I missed something here? . Heart.2013. (In press)
2. Bin Abdulhak AA, Khan AR, Tleyjeh IM, et al. Dabigatran in the
setting of catheter ablation of atrial fibrillation: the road ahead. Heart
Published Online First: [10/14/2013] doi: 10.1136/heartjnl-2013-304989
3. Konduru SV, Cheema AA, Jones P,et al. Differences in intra-
procedural ACTs with standardized heparin dosing during catheter ablation
for atrial fibrillation in patients treated with dabigatran vs. patients
on uninterrupted warfarin. J Interv Card Electrophysiol 2012; 35: 277 -
84.
4. Lakkireddy D,Reddy YM,Di Biase L,et al.Feasibility and safety of
dabigatran versus warfarin for periprocedural anticoagulation in patients
undergoing radiofrequency ablation for atrial fibrillation: results from a
multicenter prospective registry. J Am Coll Cardiol 2012;59:1168-74.
5. Bin Abdulhak AA, Khan AR, Tleyjeh IM, 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) 15 (10): 1412-1420
6. Providencia R, Albenque J-P, Combes S, et al. Safety and efficacy
of dabigatran versus warfarin in patients undergoing catheter ablation of
atrial fibrillation: a systematic review and meta-analysis. Heart
Published Online First: 22 July 2013 doi: 10.1136/heartjnl-2013- 304386.
7. Hohnloser S, Camm A. Safety and efficacy of dabigatran etexilate
during catheter ablation of atrial fibrillation: a meta-analysis of the
literature. Europace 2013;15(10):1407-11.
Thank you for your response. However, since lesion calcification
influenced incomplete revascularization, it would have been interesting to
note its effect independant of incomplete revascularization on PCI
outcomes.
I have read with interest your metanalysis on effects of
antihypertensive treatment in patients over 65 years of age, and I would
like to point to an issue quite relevant on my view. I have checked some
of the trials included because I doubted if it was possible to the authors
to separate participants with more than 65 years from younger, excluding
the latter from the analysis. For instance, in the...
I have read with interest your metanalysis on effects of
antihypertensive treatment in patients over 65 years of age, and I would
like to point to an issue quite relevant on my view. I have checked some
of the trials included because I doubted if it was possible to the authors
to separate participants with more than 65 years from younger, excluding
the latter from the analysis. For instance, in the ALLHAT study the
authors have been able to give data from participants older than 65 years
because the original paper offers that information. But looking now at the
INVEST trial, the bigger of this metanalysis excluding ALLHAT, the authors
have included all the 22576 participants. The design of INVEST included
people older than 50 years and the report explains that most of them
(15053) are under 70 years, so we can expect to have many of them under 65
years. This situation can easily have influence in the outcomes mesured
and it should have been managed properly. If we are going to speak about
older people, just data from older people should have been collected. Or,
if it were not possible to get separate data from some trials, I think it
would have been better to exclude them.
I read with great interest the recently published article by the authors Baron et al [1] on October 20, 2014 in the journal ahead of print regarding "type 2" myocardial infarction (MI) in clinical practice. One of the important findings in this large study is the outsized variation in the incidence of "type 2" MI between the reporting sites in SWEDEHEART registry. "Type 2" MI was almost nonexistent in some sites (0.2%) and as...
I read with great interest the recently published article by the authors Baron et al [1] on October 20, 2014 in the journal ahead of print regarding "type 2" myocardial infarction (MI) in clinical practice. One of the important findings in this large study is the outsized variation in the incidence of "type 2" MI between the reporting sites in SWEDEHEART registry. "Type 2" MI was almost nonexistent in some sites (0.2%) and as high as 13% of patients with MI in other sites. The main reasons for these variations, in my opinion, are that the existing definition of acute "type 1" MI is inadequate and that the definition of "type 2" MI is unclear and not evidence-based [2]. Substantial numbers of patients classified as "type 2" MI in this study have in reality no MI [2]. One of the clinical entities, which erroneously diagnosed as acute MI is takotsubo syndrome (TS). TS has a clinical presentation, ECG changes and infarction biomarker rise and/or fall resembling that of MI. TS is absolutely not MI and its histopathological features are distinct from MI. The term "type 2" MI has emerged during the last few years to describe MI secondary to an "ischemic imbalance". The diagnosis of supply and/or demand imbalance is a very subjective one and based rather on guesswork than on scientific evidence. Furthermore the conditions, which cause the presumed "decreased oxygen supply" as anemia, or respiratory failure and the conditions with supposed "increased oxygen demand", may act as a trigger factor for TS.
The second finding in the study is that patients with"type 2" MI were predominantly elderly women, had more comorbidities, smaller extent of myocardial necrosis MI and more normal coronary arteries. These findings are actually characteristic features of TS. Moreover, the inclusion of an indistinct and non-evidence-based diagnosis as "type 2" MI in SWEDEHEART registry, where the second "E" in the word is standing for "Evidence-based care", is an important limitation of the study. On the contrary to what the authors of the study believe, the true incidence of "type 2" MI, if such a diagnosis would be present, might have been overestimated in the study because it has certainly incorporated many patients with TS. For further detail about the above-mentioned arguments, the reader is referred to [2].
REFRENCES
1 Baron T, Hambraeus K, Sundstrom J, et al. Type 2 myocardial infarction in clinical practice. Heart 2014.
2 Y-Hassan S. In case of strict application, the third universal definition of myocardial infarction will erase takotsubo syndrome as a diagnosis. Inter J Cardiol 2014;176:1217-9.
Tillin et al recently reported a cohort study[1] comparing the
performance of QRISK2 and Framingham in the Southall and Brent cohort in
London. We have a number of comments on the study and the interpretation
of results.
1. Number of events : The main problem with the paper, is that
numbers are very small and given the resulting wide confidence intervals
the authors have overstated their findings. There is no...
Tillin et al recently reported a cohort study[1] comparing the
performance of QRISK2 and Framingham in the Southall and Brent cohort in
London. We have a number of comments on the study and the interpretation
of results.
1. Number of events : The main problem with the paper, is that
numbers are very small and given the resulting wide confidence intervals
the authors have overstated their findings. There is no information on how
many patients had the outcome in the different ethnic groups but there
were only 78 events in women overall, so the sub-group numbers are likely
to be extremely small. The fact that the authors reported little
difference between the two scores is likely to be due to the very wide
confidence intervals and small numbers.
2. Definition of outcome: We suspect the under-prediction of QRISK2
is due to their broader definition of the cardiovascular disease outcome
which includes HES data and patient reported outcomes. They have also
included revascularization procedures. They do not report how many events
were from different sources or an assessment of how they validated the
retrospective self-reported events. From 2014 - QRISK2 annual updates
include linked hospital episode data which increases ascertainment of
events by approximately 10%.
3. Characteristics of the cohort: The SABRE cohort largely comprised
first generation migrants with baseline measurements made over 20 years
ago. The QResearch database, which is used to develop QRISK2, includes a
nationally representative group of diverse ethnic groups many of whom will
be second or third generation at lower risk than first generation
migrants.
4. Calculation of the QRISK2 score: A number of the data items needed
to calculate a QRISK2 score were missing in their dataset. There was no
baseline information on rheumatoid arthritis, family history of premature
IHD, chronic kidney disease or atrial fibrillation. Absence of this
information is likely to have lowered discrimination. Similarly, the
cohort consisted of patients aged 40-69 which will have lowered
discrimination compared with evaluation of QRISK2 across the wider age
range of 30-84 years.
5. Reporting of performance by ethnic group. The authors mention that
the QRISK2 score has been validated in internal and external datasets but
that the performance of QRISK2 has not been reported separately by ethnic
group. We would like to draw readers attention to the QRISK-2013 update
information which was published online in April 2013 and which includes
validation statistics separately for each ethnic group[2]. The tables at
http://www.qrisk.org/QRISK2-2013-Annual-Update-Information.pdf
demonstrates good performance in all ethnic groups.
References
1. Tillin T, Hughes AD, Whincup P, et al. Ethnicity and prediction of
cardiovascular disease: performance of QRISK2 and Framingham scores in a
UK tri-ethnic prospective cohort study (SABRE--Southall And Brent
REvisited). Heart 2013 doi: 10.1136/heartjnl-2013-304474[published Online
First: Epub Date]|.
2. Hippisley-Cox J, Coupland C. QRISK2-2013 Annual Update Information,
2013:5. http://www.qrisk.org/QRISK2-2013-Annual-Update-Information.pdf
Conflict of Interest:
JR chaired, and PB was a member of, the NICE guideline
development group on cardiovascular risk assessment"The modification of blood lipids for the primary and secondary prevention of cardiovascular
disease."JHC is codirector of QRESEARCH, a not for profit organisation that is a joint partnership between the University of Nottingham and EMIS (leading supplier of information technology for 60% of UK general practices).JHC is also director of clinrisk which supplies open and closed source software to implement QRISK2.
We thank Diaz and colleagues for their positive comments on the
methodology used to develop the France-2 TAVI score. We also share their
opinion that its discrimination limits the accurate identification of
patients who are likely to die shortly after TAVI. This should, however,
be balanced by the good calibration. We agree that "the creation of an
efficient and reliable predictive model for TAVI seems to be of the
bigg...
We thank Diaz and colleagues for their positive comments on the
methodology used to develop the France-2 TAVI score. We also share their
opinion that its discrimination limits the accurate identification of
patients who are likely to die shortly after TAVI. This should, however,
be balanced by the good calibration. We agree that "the creation of an
efficient and reliable predictive model for TAVI seems to be of the
biggest challenges". Nevertheless, the means to reach this goal is not
easy and deserves comment.
Although surgical risk scores achieve good overall predictive performance,
they mix low- and high-risk patients. Their discrimination and/or
calibration decreases when applied to high-risk patients, even with the
Euroscore II (1).
A particularity of the elderly population is the frequent alteration of
functional and/or cognitive capacities which may have an impact on
outcome. A simple bedside clinical evaluation favourably compares with
current risk scores (2). A promising approach is to include variables
related to frailty in risk scores. In a series of 152 patients aged 70
years or over undergoing valvular or coronary surgery, the addition of an
indice of disability (Nagi scale) and frailty (5-meter gait speed)
increased the c-index from 0.68 to 0.73 when using the STS-PROMM score to
predict early morbidity and morbidity (3). A model was recently developed
from 2137 patients to predict 6-month poor outcome after TAVI (4). The 10
factors of this model included a mini-mental status exam and 6-minute walk
test and achieved a c-index of 0.64 in the validation sample. Therefore,
additional variables may increase the discrimination of predictive models,
but to a moderate extent. Their incremental predictive value should be
assessed in larger series and weighed against the time needed to
systematically collect additional geriatric indices.
At the present time, it remains difficult to define a core of variables
allowing for a reliable prediction of early outcome after TAVI or surgery.
Waiting for high-performance scoring systems in the elderly, if any,
current evidence supports patient selection through clinical judgement in
a Heart Team taking into account available risk scores but knowing their
limitations, as recommended in recent guidelines.
References
1. Barili F, Pacini D, Capo A, et al. Does EuroSCORE II perform better
than its original versions? A multicentre validation study. Eur Heart J
2013;34:22-9.
2. Laurent M, Fournet M, Feit B, et al. Simple bedside clinical evaluation
versus established scores in the estimation of operative risk in valve
replacement for severe aortic stenosis. Arch Cardiovasc Dis 2013;106:651-
60.
3. Afilalo J, Mottillo S, Eisenberg MJ, et al. Addition of frailty and
disability to cardiac surgery risk scores identifies elderly patients at
high risk of mortality or major morbidity. Circ Cardiovasc Qual Outcomes
2012;5:222-8.
4. Arnold SV, Reynolds MR, Lei Y, et al. Predictors of poor outcomes after
transcatheter aortic valve replacement: Results from the PARTNER
(Placement of Aortic Transcatheter Valve) trial. Circulation 2014;129:2682
-90.
Conflict of Interest:
Dr. Iung has received consultant fees from Abbott, Boehringer Ingelheim, Bayer, Valtech, and speaker's fees from Edwards Lifesciences. Dr. Himbert has received proctoring fees from Edwards Lifesciences and Medtronic. Dr. Vahanian is member of Advisory Board for Medtronic, Abbott, Valtech, and Boehringer Ingelheim, and has received speaker's fees from Edwards Lifesciences and Siemens.
Methylenetetrahydrofolate reductase (MTHFR) plays an important role
in conversion of homocysteine to methionine by catalyzing the production
of 5-methyl tetrahydrofolate hence effectively decreasing plasma
homocysteine levels. The MTHFR 677C>T nonsynonymous single nucleotide
polymorphism (SNP) leads to a substitution of Valine for Alanine and
results in the formation of a thermolabile variant of the enzyme with
decr...
Methylenetetrahydrofolate reductase (MTHFR) plays an important role
in conversion of homocysteine to methionine by catalyzing the production
of 5-methyl tetrahydrofolate hence effectively decreasing plasma
homocysteine levels. The MTHFR 677C>T nonsynonymous single nucleotide
polymorphism (SNP) leads to a substitution of Valine for Alanine and
results in the formation of a thermolabile variant of the enzyme with
decreased basal enzymatic activity (1) resulting in increased homocysteine
levels. The minor allele (T) of this SNP described in the study by
Mehling at al was found to be associated with increased plasma
homocysteine levels however the ancestral allele (C) was associated with
an increased risk for coronary artery disease (CAD)(2). This finding is
counter-intuitive and contrary to a large meta-analysis performed by Klerk
et al involving a total of 11,162 cases and 12,758 controls that found
that carriers of the minor allele T for this SNP had higher homocysteine
levels and 16% higher risk of CAD (3). The increased risk for CAD in the
TT genotype was related to lower folate concentrations.
The limitations of the study by Mehling et al are the failure to
replicate their original findings in the INTERGENE cohort and a failure to
measure folate levels. The study by Klerk et al did not find an
increased risk for CAD in the minor allele carriers who had high folate
concentrations. Another important limitation of this and other such
studies due to the homogeneous European population studied is not to
account for the racial diversity that exists with the MTHFR 677C>T
genotype. The TT genotype is common in Mexico (32%), northern China (20%)
and newborns of American Hispanic Ancestry (18%) as compared to a
prevalence of 7% in the Swedish population studied by Mehling et al which
could have accounted for the negative findings (4). Despite the higher
prevalence of this SNP in these populations, studies examining the
association of this genotype with homocysteine levels and CAD risk in
these populations are scarce. The impact of such studies if performed in
these countries or ethnic populations could potentially be far reaching by
allowing assessment of preventive measures such as folate replacement on
vascular and other complications associated with higher homocysteine
levels in subjects carrying the susceptible TT genotype.
References
(1)Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG,
Denheijer M, Kluijtmans LAJ, Vandenheuvel LP, Rozen R. A candidate genetic
risk factor for vascular disease: a common mutation in
methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111-113
(2)K Mehlig, K Leander, U de Faire, F Nyberg, C Berg, A Rosengren, L
Bj?rck, H Zetterberg, K Blennow, G Tognon, K Tor?n, E Strandhagen, L
Lissner, and D Thelle
The association between plasma homocysteine and coronary heart disease is
modified by the MTHFR 677C>T polymorphism. Heart 2013;99:1761-1765
(3)Klerk, M., Verhoef, P., Clarke, R., Blom, H. J., Kok, F. J.,
Schouten, E. G., MTHFR Studies Collaboration Group. MTHFR 677C-T
polymorphism and risk of coronary heart disease: a meta-analysis. JAMA
2002;288: 2023-2031
(4)Wilcken, B., Bamforth, F., Li, Z., Zhu, H., Ritvanen, A., Renlund,
M., Stoll, C., Alembik, Y., Dott, B., Czeizel, A. E., Gelman-Kohan, Z.,
Scarano, G., and 19 others. Geographical and ethnic variation of the 677C-
T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings
from over 7000 newborns from 16 areas world wide. J. Med. Genet. 2003;40:
619-625
We thank the Authors for the careful analysis of our work and the kind comments. In general, a distinction needs to be made when analysing clinical outcome after the Ross procedure in paediatric age. Whereas the neonatal and infant population generally presents with either isolated (often recurrent) or complex, multilevel LVOTO, which may be associated with mitral valve disease and varying degrees of LV hypoplasia, the...
Unfortunately, data with regards the presence of incomplete revascularization was available only in the Syntax study and thus this variable was not inserted in the multivariate model. Besides the aim of this analysis was to assess for clinical and anatomical variables that are available before percutaneous coronary intervention and are independent predictors of worse outcomes, since these variables can be used to stratif...
Am I missing something here? It is generally accepted that the omission of a single dose of dabigatran, which has a short elimination half-life, may place a patient at risk of thromboembolism. So why should atrial fibrillation ablation be any different especially when one is potentially stimulating thrombus formation in the left atrium during and possibly after the procedure? Why not continue the drug through the proced...
Peri-ablation dabigatran in atrial fibrillation: not only about thromboembolism.
We have read with interest the letter by Ward (1) about our recent publication (2). The author raised an important point: why should dabigatran be interrupted during a procedure known to be associated with risk of thromboembolic events? Ward also noted that our meta-analysis did not include any study with uninterrupted dabigatran....
Thank you for your response. However, since lesion calcification influenced incomplete revascularization, it would have been interesting to note its effect independant of incomplete revascularization on PCI outcomes.
Conflict of Interest:
None declared
Dear Editor,
I have read with interest your metanalysis on effects of antihypertensive treatment in patients over 65 years of age, and I would like to point to an issue quite relevant on my view. I have checked some of the trials included because I doubted if it was possible to the authors to separate participants with more than 65 years from younger, excluding the latter from the analysis. For instance, in the...
I read with great interest the recently published article by the authors Baron et al [1] on October 20, 2014 in the journal ahead of print regarding "type 2" myocardial infarction (MI) in clinical practice. One of the important findings in this large study is the outsized variation in the incidence of "type 2" MI between the reporting sites in SWEDEHEART registry. "Type 2" MI was almost nonexistent in some sites (0.2%) and as...
Tillin et al recently reported a cohort study[1] comparing the performance of QRISK2 and Framingham in the Southall and Brent cohort in London. We have a number of comments on the study and the interpretation of results.
1. Number of events : The main problem with the paper, is that numbers are very small and given the resulting wide confidence intervals the authors have overstated their findings. There is no...
We thank Diaz and colleagues for their positive comments on the methodology used to develop the France-2 TAVI score. We also share their opinion that its discrimination limits the accurate identification of patients who are likely to die shortly after TAVI. This should, however, be balanced by the good calibration. We agree that "the creation of an efficient and reliable predictive model for TAVI seems to be of the bigg...
Methylenetetrahydrofolate reductase (MTHFR) plays an important role in conversion of homocysteine to methionine by catalyzing the production of 5-methyl tetrahydrofolate hence effectively decreasing plasma homocysteine levels. The MTHFR 677C>T nonsynonymous single nucleotide polymorphism (SNP) leads to a substitution of Valine for Alanine and results in the formation of a thermolabile variant of the enzyme with decr...
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