In response to Dr. Witte's commentary, we want to provide additional
information to allay some of his concerns. Our firm opinion is that BLOCK
HF will indeed benefit the patient population included in the trial.
In his editorial, Dr. Witte states that many patients enrolled in
BLOCK HF were likely indicated for cardiac resynchronization therapy (CRT)
even before enrollment in the trial. On...
In response to Dr. Witte's commentary, we want to provide additional
information to allay some of his concerns. Our firm opinion is that BLOCK
HF will indeed benefit the patient population included in the trial.
In his editorial, Dr. Witte states that many patients enrolled in
BLOCK HF were likely indicated for cardiac resynchronization therapy (CRT)
even before enrollment in the trial. On the contrary, patients who were
indicated for CRT were excluded from the trial. Indications for CRT did
change over the duration of the trial, but at the time of enrollment, the
trial excluded patients who had contemporaneous indications for CRT.
Importantly, only 2.5% of the patients randomized as of the end of 2013
had met a contemporaneous CRT indication, while at least 15% of randomized
BLOCK HF patients progressed to a CRT indication within 12 months of
enrollment, because of progression of heart failure and ventricular
dyssynchrony.
Secondly, Witte points out that the study lacked a strong control
group, since all patients received a biventricular (BiV) device. One of
the strengths of the trial was the design. The trial could not have been a
double-blinded trial (thereby avoiding placebo effects) without implanting
all patients with CRT. All subjects had a pacing indication and thereby
would have undergone implantation of a pacing device had they not been in
the trial, unlike some CRT trials in the past such as COMPANION (1) or
CARE-HF. (2) Thus, the incremental risk of implanting the left
ventricular (LV) lead, which was turned OFF unless the subject was
randomized to the BiV arm, was the difference between what the Control arm
subjects received and what they would have received had they not been in
the trial. However, designing the trial this way did make it easier for
subjects in the Control arm to cross over to the BiV therapy arm, which
could have resulted in a reduced treatment effect in the trial.
The MOST (3) substudy showed that the risk of a heart failure
hospitalization increased progressively up to 40% ventricular pacing. In
order for patients to be included in BLOCK HF, atrioventricular (AV) block
had to be documented in their medical history or they had to fail to
conduct 1:1 during atrial pacing at 100 beats/min prior to device
implantation. Thus, patients in BLOCK HF required ventricular pacing the
great majority of the time, indicating that protocols to minimize
ventricular pacing would not be effective. Additionally, a subgroup
analysis of the varying degrees of AV block yielded a consistent effect on
the primary outcome in favor of BiV pacing. (4) While Dr. Witte suggests
that further analysis is needed in subgroups, the primary endpoint results
were consistent across all subgroups.
We agree that, in patients who have adequate AV conduction,
minimizing ventricular pacing is preferred. Pacemakers and ICDs with
ventricular pacing reduction therapies have been available since 2004, and
thus during the majority of the enrollment period of BLOCK HF, but trials
that studied the efficacy of these algorithms excluded AV block patients.
If a clinician believes that an AV block subject's ventricular pacing
percentage can be reduced below 40%, it is possible that a pacemaker or
ICD with ventricular pacing reduction algorithms may be just as effective,
but there are currently not data available to support this.
Finally, from a cost-benefit view, the study showed that 18% of
patients met a current CRT indication within one year. The REPLACE study
showed that the risk of infection and other complications during system
upgrades is nearly 19%, more than four times that of standard
replacements. LV lead-related complications occurred in 6.3% of study
patients (and not 10% as Dr. Witte states - the 10% figure is for
procedure or CRT system-related complications within 30 days).
Additionally, one could argue that the adverse events associated with LV
lead complications such as dislodgement are likely less detrimental
ultimately to a patient than those associated with heart failure
hospitalizations. BLOCK HF data suggested that the two- year mortality
risk increases from 8.8% to 41% after the first heart failure
hospitalization, and the trial suggested that implanting these patients
with CRT reduces this risk.
Anne B. Curtis, MD
University at Buffalo
Buffalo, NY
References:
Bristow MR, et al. Comparison of Medical Therapy, Pacing, and
Defibrillation in Heart Failure (COMPANION). Cardiac-Resynchronization
Therapy with or without an Implantable Defibrillator in Advanced Chronic
Heart Failure. N Engl J Med 2004; 350:2140-2150
2 Cleland JG, et al. The effect of cardiac resynchronization on
morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;
352(15):1539-49.
3 Sweeney MO, et al. Effect of pacing mode and cumulative percent
time ventricular paced on heart failure in patients with sick sinus
syndrome and baseline QRS duration less than 120 milliseconds in MOST.
PACE. 2002; 24:690.
4 Curtis AB. Editorial response to Biventricular Pacing for
Atrioventricular Block and Systolic Dysfunction. N Engl J Med 2013;
369:578-579. August 8, 2013.
Conflict of Interest:
Dr. Curtis has received honoraria from Medtronic, Inc. for consulting and speaking engagements, and
also serves on an advisory board for St. Jude Medical and has received honoraria for speaking.
Chambers et al1 give some wise recommendations regarding infective
endocarditis management. They recognize the grim prognosis of the disease
(mortality: 20-64%), the importance of dedicated teams of experts, and the
prominent role of early surgery; despite this, they suggest that some
patients can be adequately managed in centres without dedicated teams of
experts and surgical facilities, and propose nine indications for...
Chambers et al1 give some wise recommendations regarding infective
endocarditis management. They recognize the grim prognosis of the disease
(mortality: 20-64%), the importance of dedicated teams of experts, and the
prominent role of early surgery; despite this, they suggest that some
patients can be adequately managed in centres without dedicated teams of
experts and surgical facilities, and propose nine indications for transfer
patients to a surgical centre. To our opinion, every patient with
infective endocarditis should be evaluated and treated in centres with
dedicated experts and surgical facilities for several reasons: 1) severe
complications may appear at any time and may require urgent diagnosis and
treatment by experts; moreover, transferring a patient with septic shock
or acute pulmonary oedema contributes to more clinical and haemodynamic
instability; 2) an abscess, one of the indications proposed for
transferring, and other periannular complications, may be missed by non-
experts in imaging; 3) failure to respond to antibiotics is defined in the
guidelines as the persistence of positive blood cultures 7-10 days after
the initiation of antibiotic therapy2 but this arbitrary cut-off point may
be too late3; 3) emboli can be silent or with subtle symptoms and can be
easily missed even by experts; 4) severe regurgitation in the context of a
valve with important tissue damage can be difficult to assess. Our
experience is in agreement with this concept. We used to recommend that
patients could stay at their hospital if no high-risk markers were
present; eventually, some of those patients were transferred to our centre
with poorer clinical condition. Infective endocarditis is the cardiac
disease with the highest rate of death, much higher than acute myocardial
infarction and many types of cancer, which needs a combined medico-
surgical therapeutic approach, which should be undertaken at medico-
surgical centres.
1. Chambers J, Sandoe J, Ray S, et al. The infective endocarditis
team: recommendations from an international working group. Heart 2014;
100: 524-527.
2. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention,
diagnosis, and treatment of infective endocarditis of the European Society
of Cardiology. Eur Heart J 2009; 30: 2369-2413.
3. Lopez J, Sevilla T, Vilacosta I, et al. Prognostic role of
persistent positive blood cultures after initiation of antibiotic therapy
in left-sided infective endocarditis. Eur Heart J 2013; 34: 1749-54.
It is with interest that we read the paper by Buiten et al. (1) in
which the authors, using the implantable cardioverter defibrillator (ICD)
remote monitoring function in patients enrolled in the ICD-2 trial, showed
that hemodialysis (HD) is a trigger for atrial fibrillation (AF) episodes.
The study of Buiten confirms some observations we made in the recent past.
Few years ago we studied, by high frequency electrocardiograp...
It is with interest that we read the paper by Buiten et al. (1) in
which the authors, using the implantable cardioverter defibrillator (ICD)
remote monitoring function in patients enrolled in the ICD-2 trial, showed
that hemodialysis (HD) is a trigger for atrial fibrillation (AF) episodes.
The study of Buiten confirms some observations we made in the recent past.
Few years ago we studied, by high frequency electrocardiography, the
effects of the HD session on P-wave duration (Pwd), an expression of intra
-atrial conduction velocity, demonstrating that the procedure induced a
prolongation of Pwd closely related to the reduction of the plasma
potassium concentration. When the pre-and post-dialysis values of
electrolytes were put in a computational model that simulates the atrial
action potential, the atrial potential upstroke was slowed down from the
beginning towards the end of the HD session. Also we observed a reduction
of the effective refractory period (2). It is well known that both
phenomena are part of the electrical remodeling at the base of AF onset.
These data were also confirmed by a multiscale computer model (3). Buiten
et al. show that a lower concentration of potassium in the dialysis bath
(which usually is associated to a high shift of the electrolytes during
the dialysis session) is associated with a higher probability of
occurrence of AF episodes intra and peri-HD session. This observation is
concordant with our data. Recently, we reported a case of a patient in
whom HD session constantly induced episodes of paroxysmal AF. The episodes
were preceded by a reduction of the plasma potassium levels and an
increase of supraventricular ectopic beats and of the vagal component of
heart rate variability as evaluated by spectral analysis. The
computational model, feeded with the data of each session, consistently
showed an increase in atrial potential upstroke duration and a reduction
in the effective refractory period. Both phenomena were enhanced when the
IK,ACh current, sensitive to acetylcholine, was added to the model,
suggesting that the vagal rather than adrenergic stimulation plays an
important role in the genesis of intradialytic AF episodes (4). We think
that it would be very interesting to test this hypothesis using data
obtained from the remote monitoring of ICD-2 trial patients.
References
1. Buiten MS, de Bie MK, Rotmans BA et al. The dialysis procedure as a
trigger for atrial fibrillation: new insights in the development of atrial
fibrillation in dialysis patients. Heart 2014; 100: 685-690
2. Severi S, Pogliani D, Fantini G et al. Alterations of atrial
electrophysiology induced by electrolyte variations: combined
computational and P-wave analysis. Europace 2010; 12: 842-849
3. Krueger MW, Severi S, Genovesi S et al. Alterations of atrial
electrophysiology related to hemodialysis session: insights from a
multiscale computer model. J Electrocardiol 2011; 44: 176-183
4. Vincenti A, Passini E, Fabbrini P et al. Recurrent intradialytic
paroxysmal atrial fibrillation: hypotheses on onset mechanisms based on
clinical data and computational analysis. Europace 2014; 16:396-404
In a recently published Editorial to the new 2014 ACC/AHA Guidelines
for the Management of Patients with Valvular Heart Disease its authors
note that "since in asymptomatic patients decisions on timing of
intervention is made primarily on the basis of left ventricular size and
function and quantitative evaluation of mitral regurgitation severity,
accurate measurements of the left ventricular function, as well as the
deg...
In a recently published Editorial to the new 2014 ACC/AHA Guidelines
for the Management of Patients with Valvular Heart Disease its authors
note that "since in asymptomatic patients decisions on timing of
intervention is made primarily on the basis of left ventricular size and
function and quantitative evaluation of mitral regurgitation severity,
accurate measurements of the left ventricular function, as well as the
degree of MR, are essential."(1) This is now even more important than
before because the guidelines consider surgery reasonable (class IIa
indication) in the so called grade C1 asymptomatic severe mitral
regurgitation with left ventricular ejection fraction of >60% and left
ventricular end-systolic diameter of <40 mm. In such patients, as
ventricular function is normal, the decision to intervene is based almost
solely on the assessment of mitral regurgitation severity. Therefore, the
guidelines emphasize "the need to assure quality control for a
comprehensive imaging and Doppler echocardiogram, performed by experienced
laboratories, with the ability to perform accurate and reproducible
quantitative measurements of mitral regurgitation severity." However
quantitative measurements are not routinely performed even in carefully
selected tertiary referral centers, as evidenced by the results of the
recently published results of the Mitral Regurgitation International
Database (MIDA) registry, where the decisions to operate were made based
solely on semiquantitative assessment of mitral regurgitation severity.(2)
Although accepting only quantitative measurements of mitral regurgitation
severity may seem to be the solution, Biner et al. (3) recently
demonstrated that, in the group of experienced echocardiologists from
academic institutions, interobserver agreement for quantitative methods
for identifying severe from nonsevere mitral regurgitation was poor and
actually similar to the qualitative assessment (and, as stated in the
accompanying editorial, it was "more art than science"). (4) Therefore we
should be aware that, especially in asymptomatic patients with normal left
ventricular function, the probability of false positive diagnosis of
severe mitral regurgitation, based on current echocardiographic grading,
is not negligible. Therefore in such patients, with lower pre-test
probability of severe valvular lesion, a conservative approach to the
diagnosis of mitral regurgitation is always essential to decrease the
risk of performing unnecessary surgery. References: 1) Nishimura RA, Otto
C. 2014 ACC/AHA valve guidelines: earlier intervention for chronic mitral
regurgitation. Heart. 2014 online doi: 10.1136/heartjnl-2014-305834. 2)
Suri RM, Vanoverschelde JL, Grigioni F, et al. Association between early
surgical intervention vs watchful waiting and outcomes for mitral
regurgitation due to flail mitral valve leaflets. JAMA. 2013;310:609-16.
3) Biner S, Rafique A, Rafii F, Tolstrup K, Noorani O, Shiota T, Gurudevan
S, Siegel RJ. Reproducibility of proximal isovelocity surface area, vena
contracta, and regurgitant jet area for assessment of mitral
regurgitation severity. JACC Cardiovasc Imaging. 2010;3:235-43. 4)
Grayburn PA, Bhella P. Grading severity of mitral regurgitation by
echocardiography: science or art? JACC Cardiovasc Imaging. 2010;3:244-6.
The primary finding reported in this study [1] is a correlation
coefficient of -0.042 between the inflammatory marker of interleukin IL-6
and the percentage flow-mediated dilation index (FMD%). The difference
between this correlation coefficient and zero is statistically significant
(P=0.02) for the large sample of participants that was studied (n=3404).
Here we have a clear illustration of why it is important to...
The primary finding reported in this study [1] is a correlation
coefficient of -0.042 between the inflammatory marker of interleukin IL-6
and the percentage flow-mediated dilation index (FMD%). The difference
between this correlation coefficient and zero is statistically significant
(P=0.02) for the large sample of participants that was studied (n=3404).
Here we have a clear illustration of why it is important to
distinguish between clinical and statistical significance in research. The
coefficient of determination, calculated from the square of the reported
correlation coefficient, is 0.0018. This means that less than 0.2% of the
variability in FMD% is explained by the variability in IL-6.
Weiner et al.[1] reported minimum correlations to achieve statistical
significance for the various cohort sample sizes. Nevertheless, the
minimum clinically important correlation coefficient was not reported, nor
was a robust clinical anchor rationalised to interpret the findings
properly. The appraisal of clinical significance is, nevertheless,
straightforward in this study. The 95% confidence interval for a
correlation of -0.042 with a sample size of 3404 is approximately -0.08 to
-0.01. Even if the smallest worthwhile effect is as low as 0.1 ("small" by
all definitions), then the true population correlation between IL-6 and
FMD% is almost certainly trivial and not clinically important.
We were initially interested in this study because of the size-
scaling problems with the FMD% index, which were described recently, using
examples from the same MESA dataset [2]. These scaling issues are also
clearly evident in the study by Weiner et al.[1]. For example, the
apparently higher FMD% reported for women is merely because baseline
diameter (Dbase) is smaller in women, and because FMD% does not
allometrically scale for Dbase properly - illustrated, consistently in the
literature, by the negative correlation between FMD% and Dbase [2, 3, 4].
This latter correlation, which is mediated by statistical rather
physiological mechanisms, tends to be between -0.8 and -0.4, and is,
therefore, almost certainly clinically significant {2, 3, 4].
References
1. Weiner SD, Ahmed HN, Jin Z, et al. Heart Published Online First:
8th April, 2014. doi:10.1136/heartjnl-2013-304893.
2. Atkinson G, Batterham AM. The percentage flow-mediated dilation
index: A large-sample investigation of its appropriateness, potential for
bias and causal nexus in vascular medicine. Vascular Medicine 2013;18: 354
-365.
3. Atkinson G, Batterham AM. (2013b) Allometric scaling of diameter
change in the original flow-mediated dilation protocol. Atherosclerosis
2013; 226:425-427.
4. Atkinson G, Batterham AM, Thijssen DHJ, Green DJ. A new approach
to improve the specificity of flow-mediated dilation for indicating
endothelial function in cardiovascular research. J Hypertens 2013;31:287-
291.
The developers1 of the first rigorous predictive model for mortality
after transcatheter aortic valve implantation (TAVI) have overcome the
limitations of the previous surgical scores. While EuroSCORE I is an old
and redundant model based on data of 1995 and derived from a highly
heterogeneous patient group with different operations, techniques and
demographics, this predictive model is based on new results of a
remarka...
The developers1 of the first rigorous predictive model for mortality
after transcatheter aortic valve implantation (TAVI) have overcome the
limitations of the previous surgical scores. While EuroSCORE I is an old
and redundant model based on data of 1995 and derived from a highly
heterogeneous patient group with different operations, techniques and
demographics, this predictive model is based on new results of a
remarkably homogeneous population (72,4% >80 years of age and all
treated with TAVI procedures).1 Moreover, while EuroSCORE II developers
included variables that were not significantly associated with the event
by multivariate regression and did not analyze some important variables2,
Iung et al1 studied a wide variety of variables including only those
significantly associated with mortality. In addition, while in traditional
cardiac surgery there is a great disparity in results between centers
which can hamper the accuracy of any predictive model, in this study there
was no difference according to the center.1
However, and despite all these strengths, the discriminatory power
evaluated by C-index in the validation cohort was the same as that
observed when the old EuroSCORE was used (0,59). This disappointing result
means that the ability to distinguish or separate those who will die after
TAVI from those who will not is the same between a score created 15 years
ago to predict mortality after traditional surgery and a score created
nowadays and based on patients who underwent TAVI. In fact, taking into
account that a C-statistic of 0.5 indicates no predictive ability, a value
of 0,59 does not seem to be very favorable. This is more pronounced when
we consider that the promising results published by the authors of the
EuroSCORE II (C-statistic of 0,81) proved again to be disappointing when
the external validation of the model was assessed by independent
researchers2.
We agree with Ribeiro and Rod?s-Cabau3 when noting that this new model is
more accurate than some surgical scores. However, EuroSCORE II has shown
in some studies4 great calibration and better discrimination power (C-
statistic of 0,66). These authors consider the smaller number of patients
compared with surgical scores as a reason that could explain this enormous
limitation. We complete agree with this suggestion and we would like to
note that, while this system has been created based on a multivariate
analysis of 28 variables (Table 2, those with p<0,2) in a development
group of 2552 patients (253 deaths), EuroSCOCRE II was created using 26
variables in 12673 patients (587 deaths). Moreover, these authors wonder
whether a predictive model for octogenarian patients would be more
reliable taking into account a medium-term follow up. This suggestion is
supported by some works that have already confirmed this finding in
traditional surgery.5
Therefore, many more patients should be included in future models and the
performance of the system at mid-term follow up should be always tested.
However, the creation of an efficient and reliable predictive model for
TAVI seems to be one of the biggest challenges facing cardiologist and
cardiac surgeons.
REFERENCES
1. Iung B, Laou?nan C, Himbert D et al. Predictive factors of early
mortality after transcatheter aortic valve implantation: individual risk
assessment using a simple score. Heart. 2014 Apr 16. doi: 10.1136/heartjnl
-2013-305314.
2. 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.
3. Ribeiro HB, Rod?s-Cabau J. The multiparametric FRANCE-2 risk score: one
step further in improving the clinical decision-making process in
transcatheter aortic valve implantation. Heart. 2014 Apr 23. doi:
10.1136/heartjnl-2014-305806.
4. Durand E, Borz B, Godin M et al. Performance Analysis of EuroSCORE II
Compared to the Original Logistic EuroSCORE and STS Scores for Predicting
30-Day Mortality After Transcatheter Aortic Valve Replacement. Am J
Cardiol 2013;111:891-7.
5. Leontyev S, Walther T, Borger MA et al. Aortic valve replacement in
octogenarians: utility of risk stratification with EuroSCORE. Ann Thorac
Surg. 2009;87:1440-5.
We have read Ghadri et al' s article published in the issue of April
7, 2014 (1), which provide a very useful review to help us better
understand Takotsubo cardiomyopathy (TTC), a sometimes puzzling disorder.
In the "TTC TYPES" section, the authors state that TTC often affect
different left ventricular (LV) regions in the recurrent episodes. The
similar findings have been reported repetitively by other studies (2, 3)
an...
We have read Ghadri et al' s article published in the issue of April
7, 2014 (1), which provide a very useful review to help us better
understand Takotsubo cardiomyopathy (TTC), a sometimes puzzling disorder.
In the "TTC TYPES" section, the authors state that TTC often affect
different left ventricular (LV) regions in the recurrent episodes. The
similar findings have been reported repetitively by other studies (2, 3)
and found in our own TTC patients. A consistent theme appears to emerge is
that recurrent TTC tends to change its original LV contractile pattern, to
avoid significant hemodynamic compromise induced by the previous episode.
This brings up an interesting question: does the heart have a mind of its
own, to use memory imprint to protect itself?
TTC has several unique clinical features: 1) in spite of sometimes
grave presentation, it usually improves without residual cardiac
impairment, 2) although most patients with TTC appear to have poorer
systolic function than those with acute myocardial infarction (AMI), their
LV filling pressures are paradoxically lower, 3) There is significant
discrepant hemodynamic features between LV and Right ventricle (RV) (4-6).
The prevalence of RV involvement in TTC is largely underestimated,
particularly when RV apex has not been imaged sufficiently in the
echocardiographic examinations. In our TTC patients, regardless of
various LV regional involvement, RV contractile pattern in is very
constant (4-6): the basilar and middle segments of RV are hyperkinetic,
but the apical segment is hypokinetic (reverse McConnell's sign, 4). The
hyperkinesis of RV likely represents an adaptive physiologic response to
the low LV filling pressure in TTC, to maintain cardiac output. Tethering
of RV apex to an akinetic LV apex accounts for reduced RV apical motion.
This characteristic RV contractile feature helps clinically differentiate
TTC and AMI (6). More importantly, this significantly different, but also
reciprocally dependent functional status between LV and RV provides us a
hint to explore the unique pathophysiology underlying TTC.
Recent research shows that TTC is likely mediated by a switching of
epinephrine signaling transduction through the pleiotropic ?2-adrenergic
receptor from canonical stimulatory G-protein-activated cardiostimulant to
inhibitory G-protein-activated cardiodepressant pathways (7). Clinical
evidence also suggests that TTC is likely evolved as a self-protective
strategy to limit catecholamine-induced myocardial injury and reduce
hemodynamic compromise. During the acute phase of TTC, an active LV
dilation will lower filling pressure, not only protecting the vulnerable
myocardium within LV, but also preventing an abrupt increase in pulmonary
capillary wedge pressure and pulmonary edema. Meanwhile, the less
vulnerable myocardium, including RV and basilar LV walls, are activated.
These myocardial portions likely form a temporarily alternative functional
conduit that detours blood flow towards left ventricular outflow tract
(LVOT), to help maintain cardiac output, until the excessive catecholamine
surge subsides. This well-programmed interventricular
discrepancy/dependency helps maintain benign clinical courses during the
most acute TTC episodes. Heart failure/cardiogenic shock will not occur
unless some structural (e.g. basal septal hypotrophy) or functional (e.g.
dynamic LVOT obstruction) abnormalities significantly interrupt this
otherwise harmony machinery. In recurrent TTC episodes, the heart can
learn and adjust its contractile pattern to avoid affecting this key
"rescue" system, and avoid hemodynamic compromise happening again.
Therefore, maintaining appropriate LV filling pressure and avoiding
dynamic LVOT obstruction should be the main therapeutic strategies during
the acute phase of TTC (6). Unnecessary cardiac catheterization and
inappropriate pressor (such as dobutamine) treatment will potentially
disrupt the heart's self protective mechanism, and results in adverse
outcome.
Reference
1. Ghadri JR, Ruschitzka F, L?scher TF, et al. Takotsubo cardiomyopathy:
still much more to learn. Heart. 2014 Apr 7. doi: 10.1136/heartjnl-2013-
304691
2. Xu B, Williams PD, Brown M, et al. Takotsubo cardiomyopathy: does
recurrence tend to occur in a previously unaffected ventricular wall
region? Circulation. 2014;129: e339-340
3. Kaushik M, Alla VM, Madan R, et al. Recurrent stress cardiomyopathy
with variable regional involvement: insights into etiopathogenetic
mechanisms. Circulation. 2011;124:e556-e557.
4. Liu K, Carhart R. "Reverse McConnell's Sign?": A Unique Right
Ventricular Feature of Takotsubo Cardiomyopathy. Am J Cardiol 2013;11:1232
-1235.
5. Boppana S, Bhatta L, Liu K. Reversible Tricuspid Regurgitation in Acute
and Chronic Cardiomyopathies: Medical Management vs. Surgical
Intervention? J Am Coll Cardiol Img 2013;6:920-921.
6. Liu K Krone RJ. What truly causes the adverse outcome of Tako-Tsubo
cardiomyopathy? Lessons learned from echocardiography. J Am Coll Cardiol
Img 2014; (in press).
7. Paur H, Wright PT, Sikkel MB, et al. High levels of circulating
epinephrine trigger apical cardiodepression in a ?2-adrenergic receptor/Gi
-dependent manner: a new model of Takotsubo cardiomyopathy. Circulation
2012; 126:697-706.
Both valve replacing and valve sparing root replacement were devised on the operating table and evolved by trial and error. Different times set different standards. By contrast, after four years of research collaboration between surgeons, anatomists and engineers (2000-2004) personalised external aortic root support (PEARS) has followed a standard protocol in 42 patients with over 170 patient-years of intention-to-treat analysis a...
Both valve replacing and valve sparing root replacement were devised on the operating table and evolved by trial and error. Different times set different standards. By contrast, after four years of research collaboration between surgeons, anatomists and engineers (2000-2004) personalised external aortic root support (PEARS) has followed a standard protocol in 42 patients with over 170 patient-years of intention-to-treat analysis and has been systematically and rigorously evaluated.
Cameron's 'two technical points'[1] do not accurately reflect how this operation is in fact performed.[2] The proximal end of the support has a rolled margin sutured to the aorto-ventricular junction and is far stronger than required to prevent dilatation. Aortic button implantation is a site of failure in root replacement not shared by PEARS which has no sutured button. The soft pliant macroporous mesh, which we know to be histologically incorporated in the aortic adventitia, covers the transition from aorta to coronary artery without constraining it.[2] Cameron's 'revisiting' implies that PEARS is to be compared with the historical crude wrapping with stiff vascular grafts or to the Florida sleeve, both of which we consider to be quite different.
For valve sparing root replacement, cardiopulmonary bypass times were more than three hours for the majority of 239 patients in a recent prospective observational study (AVOOMP).[3] Certainly, this cannot be considered a ???short bypass time???. One year outcomes only are reported. When evaluated in a core lab 7% of patients had aortic regurgitation of at least moderate severity (???2+). The the 1 year major adverse valve related event (MAVRE) rate was 16% (35/222) and the combined 1 year MAVRE and cardiac complications event rate was 29% (65/225) [3] Cameron glosses over the documented long term composite valve related event rate for valve sparing root replacement of 1.9% per annum.[4] His 'high benchmark of surgical success' conveys complacency not warranted on examination of the facts.
Root replacement for people with Marfan syndrome has extended survival[1] and has been a surgical achievement in which we have shared but there is room for reduction in the burden that root replacement surgery places on the quality of patients' lives.[4] The technology of computer aided design is a reliable way of conserving the valve and leaving the blood/endothelial interface intact[2] compared with the 'bench mark' operation. It offers the prospect of a better quality of life for future patients.
The authors have no commercial interest in this device and received no remuneration of any kind in the development and evaluation of this device.
Reference List
1 Cameron D: External support of the dilated aorta: back to the future?; 2014.
2 Pepper J, Petrou M, Rega F, et al: Implantation of an individually computer-designed and manufactured external support for the Marfan aortic root. http://mmcts oxfordjournals org/cgi/content/full/mmt004?ijkey=WWjo5zbymFMuCWK&keytype=ref.
3 Coselli J: Early and one-year outcomes of aortic root surgery in Marfan syndrome patients. A prospective, multicentre, comparative study. J Thorac Cardiovasc Surg. 2014 Feb 8. pii: S0022-5223(14)00181-0. doi: 10.1016/j.jtcvs.2014.02.021. [Epub ahead of print].
4 Benedetto U, Melina G, Takkenberg JJ, et al: Surgical management of aortic root disease in Marfan syndrome: a systematic review and meta-analysis. Heart 2011;97:955-958.
I read with great interest the "challenge" posed by the
electrocardiographic recording in issue 7 of Heart for 2014. I also noted
with interest that the authors suggest that Monckeberg provided the first
account of such dual nodes in 1993 (their reference #1). Since Monckeberg
was long since dead by that date, this must be some mistake! I think the
appropriate date is 1913. It is certainly the case that Monckeberg was th...
I read with great interest the "challenge" posed by the
electrocardiographic recording in issue 7 of Heart for 2014. I also noted
with interest that the authors suggest that Monckeberg provided the first
account of such dual nodes in 1993 (their reference #1). Since Monckeberg
was long since dead by that date, this must be some mistake! I think the
appropriate date is 1913. It is certainly the case that Monckeberg was the
first to describe this rare anatomic arrangement. Monckeberg's heart,
however, was characterised by the presence of discordant atrioventricular
connections, and double outlet right ventricle. Since then, dual
atrioventricular nodes have been demonstrated in another heart with double
outlet right ventricle, but in the setting of concordant atrioventricular
connections (Br Heart J 1973; 35: 566-569). To the best of my knowledge,
all other hearts subsequently published with dual atrioventricular nodes
have either had isomerism of the atrial appendages (Smith et al, Cardiol
Young 2006; 16: 437-454), or else discordant atrioventricular connections,
as in the index case described by Monckeberg. Again, to the best of my
knowledge, hearts have yet to be described with dual nodes located as
shown in the cartoon provided by Paech and colleagues. It is possible that
their patient, with hypoplastic left heart syndrome, could have had a so-
called "atriofascicular tract", since that is the closest arrangement of
which I am aware that fits their cartoon.The second node in these
situations, however, is found anterolaterally within the right
atrioventricular junction (Becker et al, Circulation 1978; 57: 870-879),
rather than inferiorly as pictured in their cartoon. I wonder, therefore,
what additional information they have to prove that their patient had dual
atrioventricular nodes? On the basis of my own experience with assessing
autopsied hearts, I would be very surprised to find the arrangement that
they have depicted in a patient with hypoplastic left heart syndrome.
The paper by the JBS3 Board dismisses the role of vitamin D in
reducing risk of cardiovascular disease (CVD) since large-scale randomized
controlled trials (RCTs) have not demonstrated the benefit [1]. However, a
more recent paper from the Women's Health Initiative calcium/vitamin D RCT
did report a beneficial effect in significantly lowering low-density
lipoprotein cholesterol and raising high-density lipoprotein cholester...
The paper by the JBS3 Board dismisses the role of vitamin D in
reducing risk of cardiovascular disease (CVD) since large-scale randomized
controlled trials (RCTs) have not demonstrated the benefit [1]. However, a
more recent paper from the Women's Health Initiative calcium/vitamin D RCT
did report a beneficial effect in significantly lowering low-density
lipoprotein cholesterol and raising high-density lipoprotein cholesterol
[2]. This finding was made on the basis of 600 participants who had serum
25-hydroxyvitamin D [25(OH)D] and cholesterol levels measured at time of
enrollment and at the end of two years in the study. Serum 25(OH)D levels
were 38% higher in the active arm (mean 60.8 nmol/L) than in the placebo
arm after two years.
Evidence from observational studies strongly supports a role of
vitamin D in reducing risk of CVD. A meta-analysis of 19 observational
studies of CVD risk with respect to 25(OH)D levels found a relative risk
of 2.1 at 18 nmol/L, 1.6 at 30 nmol/L, 1.2 at 50 nmol/L, and 1.02 at 70
nmol/L [3]. The findings in Ref. 2 are in general agreement with the
findings in this meta-analysis.
The proper way to conduct vitamin D RCTs was outlined in a recent
paper. The guidelines include starting with a 25(OH)D-health outcome
relation, enrolling people with 25(OH)D levels near the low end of the
relation, supplementing with sufficient vitamin D to raise 25(OH)D levels
to the optimal level, then remeasuring 25(OH)D levels [4]. RCTs conducted
on groups with mean 25(OH)D levels above 50 nmol/L generally do not find
beneficial effects due to using too little vitamin D and having an
uncertainty larger than the expected benefit.
As to the suggestion that low 25(OH)D levels reflect or may be a
consequence of lifestyle factors rather than being a causal risk factor,
that is not correct. There will be two letters to the editor responding to
Ref. 154 (Autier et al.) published shortly in Lancet Diabetes &
Endocrinology pointing out that observational studies provide good
evidence and that all types of vitamin D studies should be considered and
evaluated using Hill's criteria for causality in a biological system.
References
1.JBS3 Board. Joint British Societies' consensus recommendations for the
prevention of cardiovascular disease (JBS3). Heart 2014;100:ii1-ii67
2. Schnatz PF, Jiang X, Vila-Wright S, et al. Calcium/vitamin D
supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol
profiles in the Women's Health Initiative calcium/vitamin D randomized
trial. Menopause. 2014 Mar 3. [Epub ahead of print]
3. Wang L, Song Y, Manson JE, et al. Circulating 25-hydroxy-vitamin D
and risk of cardiovascular disease: A meta-analysis of prospective
studies. Circ Cardiovasc Qual Outcomes. 2012;5:819-29.
4. Heaney RP. Guidelines for optimizing design and analysis of
clinical studies of nutrient effects. Nutr Rev. 2014;72:48-54.
Conflict of Interest:
I receive funding from Bio-Tech Pharmacal (Fayetteville, AR), the Sunlight Research Forum (Veldhoven) and the UV Foundation (McLean, VA).
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I read with great interest the "challenge" posed by the electrocardiographic recording in issue 7 of Heart for 2014. I also noted with interest that the authors suggest that Monckeberg provided the first account of such dual nodes in 1993 (their reference #1). Since Monckeberg was long since dead by that date, this must be some mistake! I think the appropriate date is 1913. It is certainly the case that Monckeberg was th...
The paper by the JBS3 Board dismisses the role of vitamin D in reducing risk of cardiovascular disease (CVD) since large-scale randomized controlled trials (RCTs) have not demonstrated the benefit [1]. However, a more recent paper from the Women's Health Initiative calcium/vitamin D RCT did report a beneficial effect in significantly lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholester...
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