In the interpretation of clinical trials or meta-analyses that show
no significant difference between the two comparators, one controversial
issue is the need to differentiate between "no proof of difference"
(inconclusive result) and "proof of no difference" (or demonstrated non-
inferiority). For this purpose, trial-sequential analysis (TSA) is
considered to be an appropriate statistical tool (1-4).
In the interpretation of clinical trials or meta-analyses that show
no significant difference between the two comparators, one controversial
issue is the need to differentiate between "no proof of difference"
(inconclusive result) and "proof of no difference" (or demonstrated non-
inferiority). For this purpose, trial-sequential analysis (TSA) is
considered to be an appropriate statistical tool (1-4).
In the meta-analysis by Providencia et al. comparing dabigatran vs
warfarin in patients with atrial fibrillation undergoing catheter ablation
(5), one limitation that the authors themselves have pointed out is that
"some comparisons [were] limited by the low event rates". As shown in
Figure 2 of Providencia's paper, the overall event rate in the two
patient groups was 0.3% (15/4782) for thromboembolic complications and
1.4% (67/4782) for major bleedings.
In the light of these findings, the conclusion that "the rate of
thrombolembolic complications and/or major bleeding in patients on
dabigatran.... is similar to that seen with warfarin" is not justified by
any statistical proof. In fact, if a TSA is applied to determine the
optimal information size required to reach a conclusive result from these
data, the analysis clearly shows that the number of patients actually
enrolled in the available trials (N=4,782) is much lower than the optimal
number required for evaluating thromboembolic complications (N=18,767) or
major bleedings (N=17,461); see Figure 1 at
www.osservatorioinnovazione.net/supplement/dabigatran-ablation.pdf .
Hence, the best interpretation of these results is that no conclusion
can be made on these two end-points.
References
1. Messori A, Fadda V, Maratea D, Trippoli S. Erythropoietin in
patients with acute myocardial infarction: no proof of effectiveness or
proof of no effectiveness? Clin Cardiol. 2013 Aug 8. doi:
10.1002/clc.22187. [Epub ahead of print] PubMed PMID: 23929820.
2. Messori A, Fadda V, Maratea D, Trippoli S. Intra-aortic balloon
pump in high-risk percutaneous coronary interventions without cardiogenic
shock: Trial sequential analysis of outcomes. Int J Cardiol. 2013 Jul 23.
doi:pii:S0167-5273(13)01155-8. 10.1016/j.ijcard.2013.06.098. [Epub ahead
of print] PubMed PMID: 23890904.
3. 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.
4. 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. doi:10.1001/jamainternmed.2013.6638.
5. Providencia R, Albenque JP, Combes S, Bouzeman A, Casteigt B,
Combes N, 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: 2013 Jul 22
doi:10.1136/ heartjnl-2013-304386
We read with interest the recent article on survival by stroke volume
index (SVI) in patients with low-gradient (LG) normal ejection fraction
(EF) severe aortic stenosis (AS), which demonstrated lower SVI is
incrementally associated with mortality [1].
The authors discuss a putative mechanism of low stroke volume
secondary to concentric remodeling which results in reduced LV cavity
size. This, is turn, impedes...
We read with interest the recent article on survival by stroke volume
index (SVI) in patients with low-gradient (LG) normal ejection fraction
(EF) severe aortic stenosis (AS), which demonstrated lower SVI is
incrementally associated with mortality [1].
The authors discuss a putative mechanism of low stroke volume
secondary to concentric remodeling which results in reduced LV cavity
size. This, is turn, impedes LV diastolic filling, culminating in
diminished systolic function despite EF. The authors quote evidence of
systolic impairment, e.g. reduced longitudinal strain, in similar cohorts
with preserved EF [2]. In the current study, the subgroup with lowest SVI,
and therefore presumed most severe systolic impairment despite EF >50%,
demonstrated the thickest relative wall measurements. We believe this
observation helps to explain the apparent paradox between significant
myocardial dysfunction and preservation of EF in this cohort and in the
wider 'heart failure with preserved ejection fraction' context. Recent
mathematical modeling of LV contraction has shown that both myocardial
shortening and end-diastolic wall thickness are determinants of EF [3].
Essentially, absolute LV wall thickening, as defined by the absolute
difference between wall thickness at end-systole and end-diastole, may be
nearly normal in patients with concentric LV hypertophy (LVH) because
absolute systolic thickening will be augmented in response to increased
end-diastolic LV wall thickness. As a result, the endocardial displacement
and EF will also be normal, as the external LV volume remains fairly
static throughout the cardiac cycle [4] and the absolute wall thickening
may appear to compensate for any contractile strain abnormality.
The development of concentric LVH ventricle may be viewed as a
compensatory response that normalises contractile stress and total
contractile force. However, if contractile stress remains reduced, the
contractile force will be inadequate and result in a fall in stroke volume
despite the preserved EF. In order to understand the apparent discrepancy
in SV and EF, one must distinguish between contractile strain and stress
and the relationship between end-diastolic wall thickness and EF.
The authors elected to investigate SV indexed to body surface area.
However, it would be interesting to know whether correcting EF for the
presence of concentric LVH (EFc), as described in mathematical modeling
studies of the LV [3], would be a useful prognostic marker in this cohort
of patients. After all, EFc is potentially an even more relevant
allometric indexed value given the importance of end-diastolic wall
thickness in patients with concentric LVH and systolic impairment but
preserved EF.
References:
[1] Eleid MF, Sorajla P, Michelena HI, et al. Survival by stroke
volume index in patients with low-gradient normal EF severe aortic
stenosis. Heart. Published Online First: 12 September 2014. Doi:
10.1136/heartjnl-2014-306151
[2] Adda J, Mielot C, Giorgi R, et al. Low-flow, low-gradient severe
aortic stenosis despite normal ejection fraction is associated with severe
left ventricular dysfunction as assessed by speckle-tracking
echocardiography: a multicenter study. Circ Cardiovasc Imaging 2012; 5: 27
-35.
[3] Maciver DH. A new method for quantification of left ventricular
systolic function using a corrected ejection fraction. Eur J Echocardiogr
2011; 12: 228-34.
[4] Emilsson K, Brudin L, Wandt B. The mode of left ventricular
pumping: is there an outer contour change in addition to atrioventricular
plane displacement? Clin Physiol 2001; 21: 437-446.
Acknowledgements:
NIHR Bristol Biomedical Research Unit in Cardiovascular Medicine.
The views expressed are those of the authors and not necessarily
those of the National Health Service, National Institute for Health
Research, or Department of Health.
We have read with interest the comments by Bin Abdulhak and
colleagues [1] to our recently published article [2]. We share the same
opinion concerning the use of dabigatran in this setting. Thus, in our
paper we have proposed the same posology in face of the similar findings:
despite the lack of conclusive evidence in support of any particular
dabigatran dosage or timing for interrupting or restarting drug therapy,
like...
We have read with interest the comments by Bin Abdulhak and
colleagues [1] to our recently published article [2]. We share the same
opinion concerning the use of dabigatran in this setting. Thus, in our
paper we have proposed the same posology in face of the similar findings:
despite the lack of conclusive evidence in support of any particular
dabigatran dosage or timing for interrupting or restarting drug therapy,
like Bin Abdulhak and colleagues [1], we also suggested skipping 1 or 2
doses of dabigatran before the procedure (or maybe more if renal function
was compromised) and restarting the drug 3 to 4 hours after assuring
haemostasis [2]. However, we admit that the ideal drug regimen is still an
unsolved matter, since the role of uninterrupted dabigatran may yet need
further clarification.
We agree that a randomized controlled trial of dabigatran versus warfarin
in these patients may provide further evidence and guidance. However, we
know not of any such study that is either ongoing or planned at the
moment. Furthermore, the sample of patients treated with dabigatran that
was gathered in our study (1,823 patients) provides already a reasonable
support towards the safety and efficacy of the drug.
According to the last Venice Chart international consensus document on
atrial fibrillation ablation, the use of transoesophageal echocardiography
preablation should be considered as supplementary to a backup strategy to
anticoagulation, independently of the drug used. The document also
proposes that a cardiac computed tomography scan (routinely performed in
most of the patients for anatomical purposes) may be reasonable as an
alternative [3]. This is reinforced by data of a recent meta-analysis
reporting a very high reliability and accuracy for thrombus detection
namely when delayed imaging was performed (99% sensitivity and 100%
specificity) [4]. Therefore, preprocedural imaging for exclusion of
thrombus may be justifiable, even in face of the favorable data from the
RE-LY cardioversion sub-study.
References:
1. Bin Abdulhak, A., Khan, AR. ,Tleyjeh,I.,et al. Response to: Safety and
efficacy of interrupted dabigatran for peri-procedural anticoagulation in
catheter ablation of atrial fibrillation: a systematic review and meta-
analysis. Heart. 2013 (In Press)
2. Providencia, R., Albenque, J-P., Combes, S.,et al. Heart Published
Online First: 2013 Jul 22 doi:10.1136/ heartjnl-2013-304386
3. Raviele A, Natale A, Calkins H et al. Venice Chart international
consensus document on atrial fibrillation ablation: 2011 update. J
Cardiovasc Electrophysiol. 2012;23(8):890-923. doi: 10.1111/j.1540-
8167.2012.02381.x
4. Romero J, Husain SA, Kelesidis I et al. Detection of left atrial
appendage thrombus by cardiac computed tomography in patients with atrial
fibrillation: a meta-analysis. Circ Cardiovasc Imaging. 2013;6(2):185-94.
doi: 10.1161/CIRCIMAGING.112.000153
Conflict of Interest:
RP has received honoraria for serving as a speaker and consultant for Boheringher-Ingelheim and as a co-investigator in the ENGAGE-AF TIMI 48 trial. No conflicts of interest for other co-authors.
Messori et al [1] present a very interesting matter (the difference
between inconclusive results and demonstrating non-inferiority) concerning
our recently published meta-analysis of dabigatran vs. warfarin in the
setting of catheter ablation of atrial fibrillation [2] that merits a
practical reflection.
First, proving that two treatments are equal in performance is impossible
with statistical tools; at most, one can show...
Messori et al [1] present a very interesting matter (the difference
between inconclusive results and demonstrating non-inferiority) concerning
our recently published meta-analysis of dabigatran vs. warfarin in the
setting of catheter ablation of atrial fibrillation [2] that merits a
practical reflection.
First, proving that two treatments are equal in performance is impossible
with statistical tools; at most, one can show that they are equivalent
using statistical test that aims at showing that two treatments are not
too different in characteristics, where "not too different" is defined in
a clinical manner.
In our paper, non-significant results were obtained when comparing
dabigatran with warfarin for thromboembolic complications and major
bleedings. Thus, we cannot claim that dabigatran is different in
performance than warfarin, which is our conclusion. We have evaluated the
validity of our meta-analysis and tried to control for heterogeneity of
data using several sensitivity analysis. These have shown similar results
in the differently tested scenarios [2]. Moreover, we have gathered a
great body of evidence and presented reassuring results supporting the
absence of marked differences between the two studied anticoagulant
options.
With negative results, the question is always to know if such finding is
due to lack of power or whether the new treatment is likely to be similar
to the other. Negative results often occur because the sample size is too
small, and thereby the probability of making a type II error is too large.
Trial sequential analysis (TSA) is a recently introduced statistical tool
that may be "applied to determine the optimal information size required to
reach a conclusive result". This tool has suggested in a study that
between 80 to 90% of all assessed non-significant meta-analysis might
eventually have been underpowered to that purpose [3]. This is such a big
issue.
According to the results of the Messori et al. [1], the TSA methods
applied to our meta-analysis failed in showing conclusive result because
the number of events were insufficient to construct the boundaries of
futility ('no effect'). Moreover, Messori and colleagues' estimations
would suppose to conduct a trial with more than 18.000 patients to compare
the two drugs, which is unrealistic and in face of the very low incidence
of events. Also, according to their opinion, this problem would occur to
any of the other novel anticoagulants to be tested. For example, "A Study
Exploring Two Treatment Strategies in Patients With Atrial Fibrillation
Who Undergo Catheter Ablation Therapy "(VENTURE-AF trial), comparing
rivaroxaban and warfarin, estimates an enrollement of 200 patients [4].
Additionally, the "Catheter Ablation vs Anti-arrhythmic Drug Therapy for
Atrial Fibrillation Trial" (CABANA), one of the largest catheter ablation
of atrial fibrillation trials to date, will enrol 3000 subjects during
more than 6 years [5]. However, based on the event rates observed in our
meta-analysis, for a non-inferiority trial intending to show that the
effect of a dabigatran is not worse than that of warfarin by more than a
specified margins (0.5% for thromboembolic and 0. 7% for major bleedings)
the inclusion of 4782 patients, as done in our meta-analysis, allow to
achieve around 80% power (beta=0.2) at alpha=0.05.
Final and robust answer to this important issue may be given in the next
few years, with data available from a larger number of patients included
in future trials that will allow us to make a more powerful meta-
analysis. In the meantime, with the limitations of meta-analysis
methodology previously discussed, our study shows that there is no
significant difference between dabigatran and warfarin in patients
undergoing catheter ablation of atrial fibrillation.
References:
1. Messori A, Fadda CV, Maratea D, Trippoli S. Comparing dabigatran vs
warfarin in patients with atrial fibrillation undergoing catheter
ablation: inconclusiveness of the results concerning thromboembolic
complications and major bleedings. Heart.2013 Sep 16. [EPub]
2. Providencia R, Albenque JP, Combes S, Bouzeman A, Casteigt B, Combes N
et al. Safety and efficacy of dabigatran versus warfarin in patients
undergoing catheter ablation of atrial fibrillation: a systematic review
and meta-analysis.Heart.2013 Jul 22. [Epub ahead of print]
3. Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis
reveals insufficient information size and potentially false positive
results in many meta-analyses. J ClinEpidemiol. 2008;61(8):763-9.
4. A Study Exploring Two Treatment Strategies in Patients With Atrial
Fibrillation Who Undergo Catheter Ablation Therapy (VENTURE-AF) ,
available at http://clinicaltrials.gov/show/NCT01729871
5. Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial
Fibrillation Trial (CABANA) , available at
http://clinicaltrials.gov/ct2/show/NCT00911508
Conflict of Interest:
RP has received honoraria for serving as a speaker and consultant for Boheringher-Ingelheim and as a co-investigator in the ENGAGE-AF TIMI 48 trial.
The learning points that Luther and colleagues have raised from this
case are well made. Brief limb-jerking is not uncommon during syncope and
such 'convulsive syncope' may lead to an incorrect diagnosis of epilepsy
and/or unnecessary referral to a neurology service. This misdiagnosis is
not uncommon in people with inherited cardiac conditions such as long QT
syndromes; it may delay appropriate asse...
The learning points that Luther and colleagues have raised from this
case are well made. Brief limb-jerking is not uncommon during syncope and
such 'convulsive syncope' may lead to an incorrect diagnosis of epilepsy
and/or unnecessary referral to a neurology service. This misdiagnosis is
not uncommon in people with inherited cardiac conditions such as long QT
syndromes; it may delay appropriate assessment and treatment and leave
people at risk.
Clinical guidelines on transient loss of consciousness, such as those
from NICE [1], recommend that a 12-lead ECG is recorded as part of the
initial assessment, with automated interpretation or interpretation by a
healthcare professional competent in identifying relevant abnormalities,
including QT abnormalities. The supine ECG in figure 1 shows clear
evidence of substantial QT prolongation. The rhythm recording during an
episode of syncope illustrates very well the potential benefit of the
early use of implanted event recorders in people whose syncopal episodes
are not sufficiently frequent to allow confident documentation of
symptomatic episodes with an external recorder [2].
The learning point that has not been made, and that must not be
overlooked, is the importance of referring such patients and their
families to an inherited cardiac conditions service with a view to genetic
testing of the proband and to relevant phenotypic screening and/or genetic
testing of first-degree relatives. This can allow identification of other
affected family members at risk of sudden cardiac death from which they
could be protected with appropriate treatment [3].
1. National Institute for Health and Care Excellence. Transient loss
of consciousness ('blackouts') management in adults and young people.
2010. Available at: http://www.nice.org.uk/guidance/cg109
2. Davis S, Westby M, Pitcher D, Petkar S. Implantable loop recorders
are cost-effective when used to investigate transient loss of
consciousness which is either suspected to be arrhythmic or remains
unexplained. Europace 2012; 14:402-9.
3. Priori SG, Wilde AA, Horie M et al. HRS/EHRA/APHRS Expert
Consensus Statement on the Diagnosis and Management of Patients with
Inherited Primary Arrhythmia Syndromes. Available at:
http://www.escardio.org/communities/EHRA/publications/consensus-
documents/Documents/diagnosis-management-patients-inherited-primary-
arrhythmia-syndromes.pdf.
Dorresteijn et al, (Heart 2013;99:866-872), presented a new tool, the
SMART risk score, for predicting 10 year risk of recurrence in patients
with established cardiovascular disease. This enables clinicians for the
first time to differentiate treatment within the hitherto broadly assumed
recurrence rate of at least 20% leading to guidelines that, so far, advise
maximal drug treatment for elevated risk factors for all patie...
Dorresteijn et al, (Heart 2013;99:866-872), presented a new tool, the
SMART risk score, for predicting 10 year risk of recurrence in patients
with established cardiovascular disease. This enables clinicians for the
first time to differentiate treatment within the hitherto broadly assumed
recurrence rate of at least 20% leading to guidelines that, so far, advise
maximal drug treatment for elevated risk factors for all patients alike.
Surprisingly, the authors seem to restrict its clinical use to those with
the highest risks (presumably the 23% of their cohort with remaining risks
of over 26%, fig. 2) thus aiming at correcting 'undertreatment'. With this
choice they miss the opportunity to use it also to revise possible
'overtreatment', which may have occurred in 21% of their cohort with risk
levels of 15% or lower.
We like to illustrate the relevance of an extended strategy with a
hypothetical example wherein a GP is consulted by a healthy 70 year old
male asking her support to stop his daily aspirin and statin medication.
He has been using this for 11 years, after a percutaneous coronary
intervention. He has never had an elevated blood pressure or any
cardiovascular complaints since and his Smart risk score is 15%. The GP
tells him that his age, being irreversible, has now lowered the
attributable risk of his reversible risk factors to such an extent (to
approx. 5%) that the harm of stopping his medication (leading to a
relative increase in attributable risk of approx. 35% ,or 2-3% absolute)
will not lead to an sizeable extra risk. Moreover continuing the
medication won't prevent the increasing risk of concurrent events from
other diseases. The patient, content to have overgrown most of his
corrigible risk, decides to stop.
Our problem with this example is that the argumentation around
attributable risk and remaining risk after minimising or maximizing
treatment has to come from educated guesses.
We would therefore urge the authors of the SMART risk score to support
potential users by providing more easily accessible data on these items in
order to enable them to further clarify the abstract thinking of
prevention statistics for their patients
I read with interest a study by Balt et al. (1) concluding that among
patients who underwent alcohol septal ablation (ASA) for hypertrophic
obstructive cardiomyopathy (HOCM) only 7% of patients experienced
malignant tachyarrhythmia (VT/VF) in the first post-ASA month, while no
VT/VF were observed later. I wish to support their study and comment on
our own experience dealing with this topic.
Based on multi-centre and mult...
I read with interest a study by Balt et al. (1) concluding that among
patients who underwent alcohol septal ablation (ASA) for hypertrophic
obstructive cardiomyopathy (HOCM) only 7% of patients experienced
malignant tachyarrhythmia (VT/VF) in the first post-ASA month, while no
VT/VF were observed later. I wish to support their study and comment on
our own experience dealing with this topic.
Based on multi-centre and multi-national European study (2), we know that
the development of ventricular arrhythmias early after ASA is not rare and
the early post-ASA period can be compared to the same period after acute
myocardial infarction. We found in-hospital VT/VF requiring immediate
electrical cardioversion in 1% of cases. Therefore, patients after ASA
require close ECG monitoring for at least five post-procedural days (2).
However, among patients with early post-procedural VT/VF there were no
further adverse clinical events. Thus, one may speculate that most of
early post-ASA ventricular arrhythmias are related to the procedure and
have no further clinical consequences (2).
A major concern associated with ASA is potentially increased risk of
sudden cardiac death in long-term follow-up. Recently, several studies
have demonstrated post-ASA survival similar to the expected survival of
age- and sex-matched general population (3-4). Moreover, causes of deaths
were determined with predominance of non-cardiac death (4).
Therefore, authors of the recent paper in the Heart should be
congratulated on further evidence of relative long-term safety of ASA.
1. Balt JC, Wijffels MC, Boersma LV, Wever EF, Ten berg JM.
Continuous rhythm monitoring for ventricular arrhythmias after alcohol
septal ablation for hypertrophic cardiomyopathy. Heart 2014 Jul 29.pii:
heartjnl-2014-305593.
2. Veselka J, Lawrenz T, Stellbrink C, et al. Low incidence of procedure-
related major adverse cardiac events after alcohol septal ablation for
symptomatic hypertrophic obstructive cardiomyopathy. Can J Cardiol
2013;29:1415-21.
3. Jensen MK, Prinz C, Hortskotte D, et al. Alcohol septal ablation in
patients with hypertrophic obstructive cardiomyopathy: low incidence of
sudden death and reduced risk profile. Heart 2013;99:1012-7.
4. Veselka J, Krejci J, Tomasov P, Zemanek D. Long-term survival after
alcohol septal ablation for hypertrophic obstructive cardiomyopathy: A
comparison with general population. Eur Heart J 2014;35: 2040-5.
There are a number of studies looking at resolution of mitral regurgitation in patients undergoing aortic valve replacement and there
is no reason to doubt that these findings will apply to patients undergoing
Transcutaneous Aortic Valve Implantation (TAVI) as well. Mitral regurgitation secondary to abnormal leaflets i.e. a degree of Prolapse, in patients with aortic stenosis will NEVER get better with Aortic valve intervention al...
There are a number of studies looking at resolution of mitral regurgitation in patients undergoing aortic valve replacement and there
is no reason to doubt that these findings will apply to patients undergoing
Transcutaneous Aortic Valve Implantation (TAVI) as well. Mitral regurgitation secondary to abnormal leaflets i.e. a degree of Prolapse, in patients with aortic stenosis will NEVER get better with Aortic valve intervention alone.
If the mitral is morphologically normal, a strong predictor of resolution after aortic valve intervention is rhythm. If the patient is in sinus rhythm, mitral regurgitation will improve. If however the patient is in atrial fibrillation and has an enlarged atrium, the mitral regurgitation will not improve and may even worsen after surgery. It is important that cardiology teams involved in heart valve intervention read the surgical literature - re-invention of the wheel is wasteful.
We thank Yan Qu and colleagues for their interest in our
publication.1 In our systematic review we concluded that caffeine exposure
was not associated with increased AF risk. We also have performed a
qualitative evaluation of dose-response, which uses the relative
proportions of caffeine exposure within each study and the risk of atrial
fibrillation (AF). Pooling the relative risk (RR) of low caffeine intake
from each st...
We thank Yan Qu and colleagues for their interest in our
publication.1 In our systematic review we concluded that caffeine exposure
was not associated with increased AF risk. We also have performed a
qualitative evaluation of dose-response, which uses the relative
proportions of caffeine exposure within each study and the risk of atrial
fibrillation (AF). Pooling the relative risk (RR) of low caffeine intake
from each study showed that the exposure to such doses was associated to
significantly lower AF risk, without statistical heterogeneity (I2=0%).1
Yan Qu and colleagues provided data from multivariate random-effect meta-
regression of these data.2 They found a linear dose-response with a modest
reduction of relative risk for each increase of 200 mg of caffeine intake
per day (RR 0.98, 95%CI: 0.94-1.01). Despite the gradual risk reduction
with progressive higher caffeine dose intake, the 95% confidence intervals
becomes wider, meaning that results become less precise.2 These results as
ours need to be clarified in further studies.
To conclude, Yan Qu and colleagues overall reinforce and corroborate the
main results of our systematic review, concluding that caffeine exposure
is not associated with increased risk of atrial fibrillation irrespective
of the amount of caffeine.1,2
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. Yan Qu, Dan Hu, Junqian Huang, et al. Dose-response relationship
between caffeine and risk of atrial fibrillation" Heart. 2013.
We thank Dr San Roman and colleagues for their comment on our
editorial. They suggest that all cases with endocarditis should be
referred to a reference center because the specialist expertise to monitor
their progress may not be available at general hospitals.
The typical length of intravenous antibiotic therapy for patients
with endocarditis is 4-6 weeks and beds in most cardiac centers are
limited so that...
We thank Dr San Roman and colleagues for their comment on our
editorial. They suggest that all cases with endocarditis should be
referred to a reference center because the specialist expertise to monitor
their progress may not be available at general hospitals.
The typical length of intravenous antibiotic therapy for patients
with endocarditis is 4-6 weeks and beds in most cardiac centers are
limited so that it is necessary to manage their use carefully. Some
patients are unlikely to need cardiac surgery, for example those with
uncomplicated endocarditis caused by fully sensitive oral streptococci or
those with right-sided endocarditis. It should be safe to manage these
at a general hospital provided there are close links with the cardiac
center including case-discussions by telephone and review of
echocardiography via a shared archive. Other patients, after a period of
inpatient medical therapy with or without surgical intervention, can be
managed by the reference center as outpatients with close monitoring of
continued intravenous therapy and periodic evaluation for persistent
infection or complications. Clearly local variations in practice should
evolve including specialists from the surgical center visiting the general
hospital, temporary transfer to the cardiac center for a day for a
transoesophageal echocardiogram if indicated and formulation of a
management plan. If close links between the center and the general
hospital are not feasible and if sufficient beds are available then
management of all cases at the center is reasonable.
The key to optimal treatment implicit in both our editorial and the
comment by Dr San Roman et al is that endocarditis requires specialist
involvement at presentation and at all stages of inpatient and subsequent
outpatient care.
In the interpretation of clinical trials or meta-analyses that show no significant difference between the two comparators, one controversial issue is the need to differentiate between "no proof of difference" (inconclusive result) and "proof of no difference" (or demonstrated non- inferiority). For this purpose, trial-sequential analysis (TSA) is considered to be an appropriate statistical tool (1-4).
In the met...
We read with interest the recent article on survival by stroke volume index (SVI) in patients with low-gradient (LG) normal ejection fraction (EF) severe aortic stenosis (AS), which demonstrated lower SVI is incrementally associated with mortality [1].
The authors discuss a putative mechanism of low stroke volume secondary to concentric remodeling which results in reduced LV cavity size. This, is turn, impedes...
We have read with interest the comments by Bin Abdulhak and colleagues [1] to our recently published article [2]. We share the same opinion concerning the use of dabigatran in this setting. Thus, in our paper we have proposed the same posology in face of the similar findings: despite the lack of conclusive evidence in support of any particular dabigatran dosage or timing for interrupting or restarting drug therapy, like...
Messori et al [1] present a very interesting matter (the difference between inconclusive results and demonstrating non-inferiority) concerning our recently published meta-analysis of dabigatran vs. warfarin in the setting of catheter ablation of atrial fibrillation [2] that merits a practical reflection. First, proving that two treatments are equal in performance is impossible with statistical tools; at most, one can show...
Dear Editor
The learning points that Luther and colleagues have raised from this case are well made. Brief limb-jerking is not uncommon during syncope and such 'convulsive syncope' may lead to an incorrect diagnosis of epilepsy and/or unnecessary referral to a neurology service. This misdiagnosis is not uncommon in people with inherited cardiac conditions such as long QT syndromes; it may delay appropriate asse...
Dorresteijn et al, (Heart 2013;99:866-872), presented a new tool, the SMART risk score, for predicting 10 year risk of recurrence in patients with established cardiovascular disease. This enables clinicians for the first time to differentiate treatment within the hitherto broadly assumed recurrence rate of at least 20% leading to guidelines that, so far, advise maximal drug treatment for elevated risk factors for all patie...
I read with interest a study by Balt et al. (1) concluding that among patients who underwent alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) only 7% of patients experienced malignant tachyarrhythmia (VT/VF) in the first post-ASA month, while no VT/VF were observed later. I wish to support their study and comment on our own experience dealing with this topic. Based on multi-centre and mult...
We thank Yan Qu and colleagues for their interest in our publication.1 In our systematic review we concluded that caffeine exposure was not associated with increased AF risk. We also have performed a qualitative evaluation of dose-response, which uses the relative proportions of caffeine exposure within each study and the risk of atrial fibrillation (AF). Pooling the relative risk (RR) of low caffeine intake from each st...
We thank Dr San Roman and colleagues for their comment on our editorial. They suggest that all cases with endocarditis should be referred to a reference center because the specialist expertise to monitor their progress may not be available at general hospitals.
The typical length of intravenous antibiotic therapy for patients with endocarditis is 4-6 weeks and beds in most cardiac centers are limited so that...
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