In the April 2008 issue of the Journal, Aldous (1)
reported the striking case of a young male with Libman-Sacks endocarditis
due to primary antiphospholipid syndrome (PAS) A transesophageal
echocardiogram performed on the patient revealed a 1.5 X 1.5cm aortic
valve vegetation which had apparently embolized to his left lower
extremity. A trial of anticoagulation failed to result regression of the...
In the April 2008 issue of the Journal, Aldous (1)
reported the striking case of a young male with Libman-Sacks endocarditis
due to primary antiphospholipid syndrome (PAS) A transesophageal
echocardiogram performed on the patient revealed a 1.5 X 1.5cm aortic
valve vegetation which had apparently embolized to his left lower
extremity. A trial of anticoagulation failed to result regression of the
lesion. The patient eventually underwent successful valve-sparing surgery
and was again anticoagulated.
We differ with the author’s contention that long term anticoagulation
in PAS will "usually proceed to regression of valve disease". While the
effects of anticoagulation therapy on patients with PAS and cardiac
involvement have not been extensively studied, several small recent
studies have all shown that the cardiac lesions associated with the PAS
may not respond to, or may even progress, despite, anticoagulation
therapy. In the largest prospective study of which we are aware, Turiel
et al (2) followed 47 patients with PAS over a 5 year period with serial
transesophageal echocardiography. All patients received oral
anticoagulants with or without anti-platelet therapy. Over the period of
follow-up, cardiac involvement remained unchanged in 64% (30 subjects).
Moreover, new cardiac abnormalities appeared in 36% (17 subjects). These
findings reflect the findings of other smaller series (3,4). Hence, it
would appear that anticoagulation therapy is ineffective in treating the
cardiac lesions associated with PAS.
1.Aldous S. An interesting presentation of antiphospholipid syndrome
Heart 2008; 94:421.
2.Turiel M, Sarzi-Putin P, Peretti R, Bonizzato S, Muzzupappa S,
Atzeni F et al. Five year follow-up by transesophageal echocardiographic
studies in primary antiphosphospholipid syndrome. Am J Cardiol
2005;96:574-9.
3.Espinola-Zavaleta N, Vargas-Barron J, Colmenares-Galvis,T, Cruz-
Cruz F, Romero-Cardenas A, Keirns C et al. Echocardiographic evaluation of
patients with primary antiphospholipid syndrome. Am Heart J 1998;137:974-
9.
4.Espinola-Zavaleta N, Montes RM, Soto ME, Vanzzini NA, Amigo MC.
Primary antiphospholipid syndrome: a 5-year transesophageal
echocardiographic follow-up study. J Rheumatol 2004;31:2402-7.
I am puzzled by the image published by Chirillo et al.(1) which
supposedly shows a "discrete aortic dissection", but - according to the
authors - no intimal flap.
My interpretation of the provided image would be that the hazy
horizontal line which runs through the middle of the aorta most likely
represents a typical intimal flap separating a true lumen (lower part)
from the false lumen (w...
I am puzzled by the image published by Chirillo et al.(1) which
supposedly shows a "discrete aortic dissection", but - according to the
authors - no intimal flap.
My interpretation of the provided image would be that the hazy
horizontal line which runs through the middle of the aorta most likely
represents a typical intimal flap separating a true lumen (lower part)
from the false lumen (with the intimal splitting tear, upper part). A
cineloop including both short-axis and longitudinal views, as well as a
colour-Doppler study might help to identify the intimal flap more clearly.
In addition, the arrow pointing to "periaortic effusion"(PE) is
obviously misplaced.
With best regards,
Ole-A. Breithardt
(1) F Chirillo, L Salvador, and F Bacchion. Acute discrete dissection
of the ascending aorta. Heart 2008; 94: 924
We have read with interest the article of Mascherbauer et al.[1]
recently published in Heart and we congratulate our colleagues for an
honest effort on shedding some light on an important issue which is still
generating some controversy. Nonetheless, based on the title and the
conclusions of both the abstract and the paper, we are concerned that the
paper may unfortunately convey the wrong message i....
We have read with interest the article of Mascherbauer et al.[1]
recently published in Heart and we congratulate our colleagues for an
honest effort on shedding some light on an important issue which is still
generating some controversy. Nonetheless, based on the title and the
conclusions of both the abstract and the paper, we are concerned that the
paper may unfortunately convey the wrong message i.e. that moderate
prosthesis-patient mismatch should never be a concern in patients
undergoing aortic valve replacement. Moreover, from the introduction,
justification for the study appears to be based on the perception that our
previous papers were recommending “that even left ventricular outflow
tract enlargement may be justified to prevent moderate PPM”. In fact, we
have never made such an unqualified recommendation. Indeed, our findings
as well as those of others [2] show that the impact of moderate PPM on
outcomes is most significant in patients with LV dysfunction as compared
to patients without dysfunction (e.g. early mortality = 16% vs 5%, p<
0.001) and our recommendation has always been that if PPM is anticipated,
alternative options should be considered in light of the patient’s overall
clinical condition and the risk to benefit ratio of doing such procedures.
Unfortunately, the number of patients with LV dysfunction in the present
study is too small to do any analysis in this regard. Moreover, LV
dysfunction might even be a confounding variable since it was
significantly more prevalent (15.2% vs 5.6%, p = 0.003) in the patients
without PPM and hence, it could explain the relatively high mortality
observed in this group (5.5%). Indeed, operative mortality for AVR in
patients without LV dysfunction is usually 1-4% and if such had been the
case, the markedly higher operative mortality (10.2%) observed in the
group with PPM might have become statistically significant.
Notwithstanding this consideration, the statistical power of the study is
clearly limited. Indeed, the difference in short-term mortality (5.5% vs.
10.2%) between the 2 groups did not reach statistical significance (i.e.
p=0.14 with Yates correction in the results section and in Table 4, or
p=0.098 without Yates correction in the Table 3). However, considering the
previous study of Blais et al. [3] for sample size estimation, the
inclusion of 361 patients leads to a statistical power of only 43% for the
analysis of operative mortality. Moreover, using the same percentage of
operative mortality in the two groups, but with a sample size of 880
patients (i.e. corresponding to the number of patients which would have
result in a 80% a priori statistical power), the p-value would have been
of 0.009 (without Yates correction). Hence, had the same sample size been
closer to that of previous series, the findings and conclusions of the
paper could have been entirely different.
Furthermore, as opposed to the perception given in the article of
Mascherbauer et al., aortic root enlargement is certainly not the only
and/or first line option to avoid PPM. The preventive strategy should
rather be focused primarily on the implantation of prosthesis models
providing a better hemodynamic performance and thereby a larger EOA in
relation to patient’s annulus size. And in this regard, several recent
studies have demonstrated that PPM can successfully be avoided or its
severity reduced with the use of such strategy. [4-6]
Given these limitations, the present paper provides little new information
and the findings certainly do not justify the unqualified conclusion that
moderate PPM has no impact on short or long term mortality which implies
that it can almost be ignored. To the contrary, we reiterate that the
projected indexed EOA should always be calculated at the time AVR and that
the decision with regards to the prosthesis to be implanted should be made
in light of the patient’s overall clinical condition.
Clearly and based on
many concurring data in the literature, every effort should be made to
avoid severe PPM in every patient undergoing aortic valve replacement and
moderate PPM if LV dysfunction and/or severe LVH is present. Finally, it
should be mentioned that the underestimation of EOA in bi-leaflet
prosthesis is based on in vitro studies and that this has not been shown
to be a consistent finding in vivo. Indeed, recent studies using either
the indexed EOA measured at predischarge exam or the projected indexed EOA
derived from in vivo reference values demonstrated that the same cut-off
values for indexed EOA were valid to predict outcomes in their series of
patients with bi-leaflet mechanical prosthesis. [7;8]
Moreover, in one of
these studies, even a moderate PPM was shown to negatively impact long-
term survival after adjustment for other risk factors. [8]
References
[1]. Mascherbauer J, Rosenhek R, Fuchs C, Pernicka E, Klaar U, Scholten C, Heger M, Wollenek G, Maurer G, Baumgartner H. Moderate patient
-prosthesis mismatch after valve replacement for severe aortic stenosis
has no impact on s.
Heart. 2008.
[2]. Ruel M, Al-Faleh H, Kulik A, Chan K, Mesana TG, Burwash IG. Prosthesis-patient mismatch after aortic valve replacement primarily
affects patients with pre-existing left ventricular dysfunction: Impact on
survival, freedom from heart failure, and left ventricular mass
regression.
J Thorac Cardiovasc Surg. 2006;131:1036-1044.
[3]. Blais C, Dumesnil JG, Baillot R, Simard S, Doyle D, Pibarot P. Impact of prosthesis-patient mismatch on short-term mortality after aortic
valve replacement.
Circulation. 2003;108:983-988.
[4]. Bleiziffer S, Eichinger WB, Hettich I, Guenzinger R, Ruzicka D,
Bauernschmitt R, Lange R. Prediction of valve prosthesis-patient mismatch
prior to aortic valve replacement: which is the best method?
Heart.
2007;93:615-620.
[5]. Dalmau MJ, Gonzalez-Santos JM, Lopez-Rodriguez J, Bueno M,
Arribas A, Nieto F. One year hemodynamic performance of the Perimount
Magna pericardial xenograft and the Medtronic Mosaic bioprosthesis in the
aortic position: a prospective randomized study.
ICVTS. 2007;6:345-349.
[6]. Kunadian B, Vijayalakshmi K, Thornley AR, de Belder MA, Hunter
S, Kendall S, Graham R, Stewart M, Thambyrajah J, Dunning J. Meta-analysis
of valve hemodynamics and left ventricular mass regression for stentless
versus stented aortic valves.
Ann Thorac Surg. 2007;84:73-78.
[7]. Mohty D, Malouf JF, Girard SE, Schaff HV, Grill DE, Enriquez-
Sarano ME, Miller FA, Jr. Impact of prosthesis-patient mismatch on long-
term survival in patients with small St. Jude medical mechanical
prostheses in the aortic position.
Circulation. 2006;113:420-426.
[8]. Kohsaka S, Mohan S, Virani S, Lee VV, Contreras A, Reul GJ,
Coulter SA. Prosthesis-patient mismatch affects long-term survival after
mechanical valve replacement.
J Thorac Cardiovasc Surg. 2008,135:1076-80.
We appreciate the interest of Rosa et al in our study.[1] They raise
3 points with respect to our results.[2] The first queries whether we had
left out the subjects dropped out during the course of the study, which
might have overestimated the clinical effectiveness of the treatment arms.
The second deals with the additional beneficial effects of irbesartan and
ramipril beyond their blood pressure c...
We appreciate the interest of Rosa et al in our study.[1] They raise
3 points with respect to our results.[2] The first queries whether we had
left out the subjects dropped out during the course of the study, which
might have overestimated the clinical effectiveness of the treatment arms.
The second deals with the additional beneficial effects of irbesartan and
ramipril beyond their blood pressure control. The third concerns the
calculation of LV mass based on dimensions of the left ventricle at end-
diastole.
All our patients were analyzed on the basis of intention-to-treat,
including all the cases up to their pre-defined follow-up at week 12, 24
or 52 before their withdrawal for various reasons as stated in the results
section. The unequal randomization of patients into the three treatment
arms that might have given Rosa et al a false impression of excluding drop
-out cases for the analysis was due to our original intention of enrolling
400 patients with designated sequence of random allocation. The
recruitment process was slow for reasons as mentioned in the limitations
section. As the result, the sample of patients recruited for the three
arms were unfortunately relatively small and, therefore, we were unable to
detect any significant changes in terms of LV mass by 2-dimensional
echocardiography. This issue warrants further study with a larger cohort
of patients.[3]
It is tantalizing to speculate that irbesartan with or without
ramipril have additional beneficial effects on the myocardium and
peripheral vascular endothelium beyond blood pressure control in patients
suffering from heart failure with normal ejection fraction (HFNEF). For
example, the relationship between arterial compliance and diastolic
dysfunction is clearly important. [4]. However this interesting notion
will require proof in HFNEF patients and deserves a further large-scale
prospective randomized study, given the magnitude of this vexing clinical
problem in Hong Kong and worldwide.[5,6]. Interestingly we found that
cough was much less of a problem than predicted in an Asian population and
our cough rate in the ramipril group (10%) is comparable to previous
studies in the West.
The comments on the effect of diuretics on left ventricular dimension
are well taken and relevant but the formula we used is well established
and widely used. Furthermore, all three patient groups received diuretics
so the effect would have been similar. Future studies could use 3D-
echocardiography or MRI for more accurate assessment of LV mass.
References
1. Rosa EM, Träsel HAV, Gravina LB. Interesting findings in The Hong Kong Heart Failure Study.
Heart 2008
eLetters Online 24 May 2008
2. Yip GW, Wang M, Wang T, et al. The Hong Kong diastolic heart failure study: a randomised controlled trial
of diuretics, irbesartan and ramipril on quality of life, exercise
capacity, left ventricular global and regional function in heart failure
with a normal ejection fraction.
Heart. 2008;94:573-80.
3. Carson P, Massie BM, McKelvie R, et al. The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design.
J Cardiac Fail 2005;11:576–585.
4. P M Mottram, B A Haluska, R Leano, S Carlier, C Case, and T H
Marwick Relation of arterial stiffness to diastolic dysfunction in hypertensive
heart disease
Heart 2005; 91: 1551 - 1556.
5. Yip GWK, Ho PPY, Woo KS, Sanderson JE Comparison of frequencies of left ventricular systolic and diastolic heart
failure in Chinese living in Hong Kong.
Am J Cardiol 1999;84:563-567.
6. Sanderson JE. Heart failure with a normal ejection fraction.
Heart. 2007;93:155-8.
Patients with heart failure and a normal left ventricular systolic
function correspond to almost half of all patients with congestive heart
failure(1). However, the great majority of the data presented in the
medical
literature are related to studies that observe subjects with heart failure
followed by systolic dysfunction. It is notable that Yip et al. (2) in
their article assess the quality of l...
Patients with heart failure and a normal left ventricular systolic
function correspond to almost half of all patients with congestive heart
failure(1). However, the great majority of the data presented in the
medical
literature are related to studies that observe subjects with heart failure
followed by systolic dysfunction. It is notable that Yip et al. (2) in
their article assess the quality of life and global and regional
ventricular function in heart failure with normal ejection fraction.
After reading with interest The Hong Kong Heart Failure Study(2), we
considered this study revealed important findings and, among those, three
have caught our attention:
1. The subjects who left the study due to adverse effects were not
included in final analysis and, consequently, did not provide changes in
final results. According to Fischer et al.(3), clinical effectiveness
may be overestimated if an intention to treat analysis is not done.
2. Both drugs Irbesartan and Ramipril do not play their roles like
anti-hypertensive agents, as should be expected(4), neither do they
present
adverse events, like irritative coughs.
3. Ventricular mass is inferred from a mathematical calculation,
which depends on intraventricular diameter(5). The usage of diuretics
decreases preload, consequently, there is a decrease in left ventricle
internal diameter. Mathematically speaking, a reduction in ventricular
mass
occurs. This effect may not be reproduced if a direct anatomic
analysis was conducted.
References
(1) Sanderson JE. Heart failure with a normal ejection fraction.
Heart. 2007 Feb; 93(2):155-8.
(2) Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, et al. The Hong Kong diastolic heart failure study: a randomised controlled trial
of
diuretics, irbesartan and ramipril on quality of life, exercise capacity,
left ventricular global and regional function in heart failure with a
normal ejection fraction.
Heart. 2008 May; 94(5):573-80.
(3) Fisher L, Dixon D, Herson J, Frankowski R, Hearon M, Pearce K. Intention to treat in clinical trials.
In: Pearce K, editor. Statistical issues in drug research and development.
New York: Marcel Dekker; 1990: 331-50.
(4) Franklin S, Lapuerta P, Cox D, Donovan M. Initial combination therapy with irbesartan/hydrochlorothiazide for
hypertension: an analysis of the relationship between baseline blood
pressure and the need for
combination therapy.
J Clin Hypertens (Greenwich). 2007 Dec; 9(12 Suppl 5):15-22.
(5) Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E,
Pellikka PA, et al. Recommendations for chamber quantification: a report from the American
Society of Echocardiography's Guidelines and Standards Committee and the
Chamber Quantification Writing Group, developed in conjunction with the
European Association of Echocardiography, a branch of the European Society
of Cardiology.
J Am Soc Echocardiogr. 2005 Dec; 18(12):1440-63.
We read with great interest the article by Yip and colleagues,
reporting the results of a randomised controlled trial of diuretics,
irbesartan and ramipril in patients with heart failure and normal ejection
fraction(1). The authors are to be commended for their contribution to
the evidence base for the management of this condition. The PROBE design
tested the hypothesis that addition of ramipril or...
We read with great interest the article by Yip and colleagues,
reporting the results of a randomised controlled trial of diuretics,
irbesartan and ramipril in patients with heart failure and normal ejection
fraction(1). The authors are to be commended for their contribution to
the evidence base for the management of this condition. The PROBE design
tested the hypothesis that addition of ramipril or irbesartan would be
superior to diuretics alone and evaluated quality of life, exercise
capacity, ventricular function and NT-pro-BNP levels in three groups of 50
patients. Quality of Life Score ( Minnesota Heart Failure Symptom
Questionnaire) improved significantly and similarly in all three groups
between baseline and 52 weeks. Exercise capacity assessed by 6 minute walk
test at baseline and 24 weeks improved only slightly. The authors suggest
that this may be because the test is not robust enough to identify
effective treatment or that older patients have too many competing factors
which influence mobility.
Our experience differs from this. The Perindopril in Elderly People with
Chronic Heart Failure (PEP-CHF) trial compared the effects of perindopril
and placebo in 850 patients >70 years of age or older,( mean age 76)
who had heart failure and echocardiographic markers suggesting diastolic
heart failure(2). Perindopril reduced heart failure hospitalisations and
improved symptoms at one year. There was also a statistically significant
increase in 6 minute walk distance in patients assigned to perindopril
over 1 year of follow up, with a mean difference in change of 14m (3 to
25, p<0.011)(3). A change of this magnitude is both statistically
significant and clinically relevant.
The baseline characteristics of patients in both studies were very
similar, although patients in PEP-CHF were slightly older, had a higher
prevalence of prior myocardial infarction and their baseline exercise
capacity was poorer. Despite this, important benefits in function were
seen in PEP-CHF with active treatment. The Hong Kong Study evaluated 6
minute walk distance after 24 weeks of treatment and it is possible that
this was too short a time for effects on exercise capacity to be
demonstrable.
The 6 minute walk distance has previously been evaluated in frail,
older patients with heart failure (4). O’Keefe’s study included frail
patients with multiple comorbidity, median age 81 years (range 74-92
years) and showed that the 6 minute walk test was both reproducible and
responsive.
We agree entirely with the authors that, particularly for older
patients, improvements in symptoms and exercise capacity are as important
as mortality benefits, and would encourage clinicians to use the 6 minute
walk test as a simple and meaningful outcome measure in heart failure.
REFERENCES
1. Yip GWK, Wang M, Wang T et al. The Hong Kong diastolic heart
failure study: a randomised controlled trial of diuretics, irbesartan and
ramipril on quality of life, exercise capacity, left ventricular global
and regional function in heart failure with a normal ejection fraction.
Heart 2008;94:573-80.
2.Cleland JGF, Tendera M, Adamus J et al Perindopril for elderly people
with heart failure: the PEP-CHF Study.
Eur J Heart Fail 2001;1:211-17
3.Cleland JGF, Tendera M, Adamus J et al The perindopril in elderly people
with chronic heart failure (PEP-CHF) study
Eur Heart J 2006;27:2338-45
4. O’Keeffe ST, Lye M, Donellan C et al. Reproducibility and
responsiveness of quality of life assessment and six minute walk test in
elderly heart failure patients.
Heart 1998;80:377-382.
We read the interesting secondary analysis of the 4.9-year Treating
to New Targets (TNT) study [1] reporting on the effects of aggressive low-
density lipoprotein (LDL) cholesterol lowering in women (median age of
63.5 years) with stable coronary heart disease. Based on the reported
data, we have serious concerns regarding the large excess in cancer
mortality seen among the women randomized to high-d...
We read the interesting secondary analysis of the 4.9-year Treating
to New Targets (TNT) study [1] reporting on the effects of aggressive low-
density lipoprotein (LDL) cholesterol lowering in women (median age of
63.5 years) with stable coronary heart disease. Based on the reported
data, we have serious concerns regarding the large excess in cancer
mortality seen among the women randomized to high-dose atorvastatin (80 mg
daily) therapy compared to the women randomized to low-dose (10 mg daily)
atorvastatin therapy (p = 0.004). Alarmingly, annualized cancer mortality
was 1 in 1000 patients in the low-dose atorvastatin group and 4 in a 1000
patients in the high-dose group. Unfortunately, there was a trend towards
increased all-cause mortality in the high-dose compared to the low-dose
atorvastatin group, neutralizing any benefit in cardiovascular mortality.
A recent meta-analysis of large randomized statin trials has revealed
a significant inverse relationship between achieved LDL-cholesterol levels
and cancer incidence [2]. Statins have been shown to significantly
increase peripheral regulatory T cell (Treg) concentration, in vivo, by
inducing the transcription factor, forkhead box P3 [3]. An increase in
Treg concentration may impair host anti-tumor response by suppressing
tumor specific effector T cell responses leading to an increase in cancer
[4]. Not surprisingly, in many solid tumors, an increased Treg
concentration predicts a significant reduction in patient survival [5].
Interestingly, estrogens also have been found to significantly
increase Treg concentration [6]. Therefore, the combination of statins and
estrogens may be particularly potent in raising Treg levels. This begs the
question: Was the increase in cancer seen in the high-dose atorvastatin
treated group, predominantly seen among those women whom were also taking
estrogens? Perhaps, the investigators can provide that answer. This is
important, since many women are treated with both statins and estrogens.
Additionally, a synergism between statins and estrogen in raising Treg
levels may explain why an increase in cancer mortality in the TNT trial
was seen among women, but not among men randomized to the high-dose
atorvastatin group [1]. Finally, we feel that high-dose atorvastatin
therapy be avoided in women because of the increased risk of subsequent
cancer death.
References
[1] Wenger NK, Lewis SJ, Welty FK, et al, on behalf of the TNT Steering Committee and Investigators. Beneficial effects of aggressive low-density lipoprotein cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study.
Heart 2008; 94: 434-439.
[2] Alsheikh-Ali AA, Maddukuri PV, Han H, et al. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized trials.
J Am Coll Cardiol 2007; 50: 409-418.
[3] Mausner-Fainberg K, Luboshits G, Mor A, et al. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells.
Atherosclerosis 2008; 197: 829-839.
[4] Curiel TJ. Tregs and rethinking cancer immunotherapy.
J Clin Invest 2007; 117: 1167-1174.
[5] Yakirevich E, Resnick MB. Regulatory T lymphocytes: pivotal components of the host antitumor response.
J Clin Oncol 2007; 25: 2506-2508.
[6] Prieto GA, Rosenstein Y. Oestradiol potentiates the suppressive function of human CD4+CD25+ regulatory T cells by promoting their
proliferation.
Immunol 2006; 118: 58-65.
Chen et al., present the results of a non-randomised prospective
study, in which individual struts in 28 stents implanted in 26 lesions in
24 patients were assessed by OCT. The authors report strut apposition and
coverage as binary variables and pool strut-related observations to
produce percentages of incompletely apposed/uncovered struts for stents
types. It is evident that individual observatio...
Chen et al., present the results of a non-randomised prospective
study, in which individual struts in 28 stents implanted in 26 lesions in
24 patients were assessed by OCT. The authors report strut apposition and
coverage as binary variables and pool strut-related observations to
produce percentages of incompletely apposed/uncovered struts for stents
types. It is evident that individual observations related strut coverage
or strut-to-intima distance violate the fundamental assumption of
independence of observations required for the application of classical
statistical methods. Struts within lesions, in fact, share common
characteristics, making them more similar to each other than to struts
from different lesions. Ignoring this multilevel structure results in
spuriously low estimated standard errors and p-values.
Similarly, when assessing neontimal thickness (NIT), Chen et al.
measure maximal and minimal NIT for each strut and produce summary
statistics at stent level by compiling these values into means.
Subsequently, they recompile the means to produce “means of means” and
compare these between stent groups using standard statistical tools. The
use of summary statistics ignores the variation at strut level and the
precision of the cluster estimate. Moreover, this can only be used for
data with a 2-level structure and, thus, not in cases such as the present
study in which more than one lesion belong to the same patient (3-level
structure: struts clustered within lesions clustered within patients).
Optical coherence tomography (OCT) has revolutionised intracoronary
imaging, providing a unique insight into all aspects of coronary stenting.
Realisation of the multilevel structure of OCT data on coronary stenting
is essential to the design, reporting and critical appraisal of all stent
-related OCT research. To ignore this, could have disastrous effects on
the validity of any statistical analysis and, eventually, on the
credibility of the technique itself.
REFERENCES
(1) B X Chen, F Y Ma, W Luo, J H Ruan, W L Xie, X Z Zhao, S H Sun, X M Guo, F Wang, T Tian, and X W Chu Neointimal coverage of bare-metal and sirolimus-eluting stents evaluated with optical coherence tomography Heart 2008; 94: 566-570
Patients with heart failure and a normal left ventricular systolic
function correspond to almost half of all patients with congestive heart
failure(1). However, the great majority of the data presented in medical
literature are related to studies that observe subjects with heart failure
followed by systolic disfunction. It is notable that Yip et al. (2) in
your article assess the quality of life and...
Patients with heart failure and a normal left ventricular systolic
function correspond to almost half of all patients with congestive heart
failure(1). However, the great majority of the data presented in medical
literature are related to studies that observe subjects with heart failure
followed by systolic disfunction. It is notable that Yip et al. (2) in
your article assess the quality of life and global and regional
ventricular function in heart failure with normal ejection fraction.
After reading with interest The Hong Kong Heart Failure Study(2), we
considered this study revealed important findings and, among those, three
have caught our attention:
1. The subjects who left the study due to adverse effects were not
included in final analysis and, consequently, did not provide changes in
final results. In according to Fischer et al.(3), clinical effectiveness
may be overestimated if an intention to treat analysis is not done.
2. Both drugs Irbesartan and Ramipril do not play their roles like
anti-hypertensive agents, as should be expected(4-9), neither they present
adverse events, like irritative coughs.
3. Ventricular mass is inferred from a mathematical calculation,
which depends on intraventricular diameter(10). The usage of diuretics
decreases preload, consequently, there is a decrease in left ventricle
intern diameter. Mathematically speaking, a reduction on ventricular mass
occurs. This effect maybe would not be reproduced if a direct anatomic
analysis was conducted.
References
(1) Sanderson JE. Heart failure with a normal ejection fraction. Heart. 2007 Feb;93(2):155-8.
(2) Yip GW, Wang M, Wang T, Chan S, Fung JW, Yeung L, et al. The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction. Heart. 2008 May;94(5):573-80.
(3) Fisher L, Dixon D, Herson J, Frankowski R, Hearon M, Pearce K. Intention to treat in clinical trials. In: Pearce K, editor. Statistical issues in drug research and development. New York: Marcel Dekker; 1990: 331-50.
(4) Franklin S, Lapuerta P, Cox D, Donovan M. Initial combination therapy with irbesartan/hydrochlorothiazide for hypertension: an analysis of the relationship between baseline blood pressure and the need for combination therapy. J Clin Hypertens (Greenwich). 2007 Dec;9(12 Suppl 5):15-22.
(5) Raskin P, Guthrie R, Flack J, Reeves R, Saini R. The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide. J Hum Hypertens. 1999 Oct;13(10):683-7.
(6) Lapuerta P. Irbesartan/HCTZ as initial treatment in patients with
moderate hypertension. 16th Meeting of the European Society of Hypertension; 2006; Madrid, Spain; 2006.
(7) Neutel JM, Franklin SS, Lapuerta P, Bhaumik A, Ptaszynska A. A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension. J Hum Hypertens. 2008 Apr;22(4):266-74.
(8) Heidbreder D, Froer KL, Breitstadt A, Cairns V, Langley A, Bender N. Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy. Clin Cardiol. 1992 Dec;15(12):904-10.
(9) Genthon R. Study of the efficacy and safety of the combination
ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group. Int J Clin Pharmacol Res. 1994;14(1):1-9.
(10) Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report
from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005 Dec;18(12):1440-63.
Kaski et al. (1) recently reported that in children with hypertrophic
cardiomyopathy (HC) the B-type natriuretic peptide (BNP) level correlated
with maximal left ventricular (LV) wall thickness and could be a useful
tool in assessing disease severity. In adult patients with HC, circulating
plasma BNP has been related to the magnitude of heart failure and can be
used to detect HC in patients when symp...
Kaski et al. (1) recently reported that in children with hypertrophic
cardiomyopathy (HC) the B-type natriuretic peptide (BNP) level correlated
with maximal left ventricular (LV) wall thickness and could be a useful
tool in assessing disease severity. In adult patients with HC, circulating
plasma BNP has been related to the magnitude of heart failure and can be
used to detect HC in patients when symptom evaluation is difficult (2).
Here we further demonstrate the role of BNP in newborn babies affected by
Pompe disease.
We detect Pompe disease (acid alpha-glucosidase deficiency) in
newborns though large-scale newborn screening (manuscript in press). We
totally identified five patients at a median age of 0.75 months (range:
0.25-1 month) and none of them showed symptoms like feeding difficulty,
dyspnea, or muscle weakness at the time of diagnosis. However, their
median left ventricular mass index (LVMI) was 120.3 g/m2 (range: 108.9-186
g/m2; normal levels, 47.4 +/-6.2 g/m (3)), and mean BNP level was as high
as 556.97 pg/mL (range: 420.37-1300 pg/mL, normal babies less than one
month of age: median 28.61 pg/mL, 97.5th percentile 169.10 pg/mL, n=23).
After receiving two infusions biweekly of human recombinant acid alpha-
glucosiase (Myozyme, Genzyme), their median BNP level dropped to 16.35
pg/mL (range 0-77 pg/mL).
We observed a positive correlation between BNP and LVMI (correlation
coefficient=0.63) in the five babies detected by screening. We also
examined BNP and LVMI in four older infants with Pompe disease who were
diagnosed by clinical symptoms. In comparison with the newborn cases,
those patients were discovered at a later age (median: 3.1 months, range:
1.8-4 months, p=0.016), tended to have higher LVMI (median: 189.1 g/m2,
range: 151.6-307.5 g/m2, p=0.19), but lower median BNP level (412.6 pg/mL,
range: 132.8-5190.5 pg/mL, p=0.556). However, the correlation between BNP
and LVMI was very high (correlation coefficient=0.92). After 2 doses of
Myozyme, their median BNP level dropped to 70.86 pg/mL (range: 12.45-
724.09 pg/mL), slightly higher than the babies detected by screening
(p=0.016).
Our observation suggests that in Newborns with Hypertrophic
Cardiomyopathy due to Pompe disease, BNP is not only a good marker to
monitor the treatment for HC, but also a very useful tool to make early
diagnosis of Pompe disease, before the appearance of skeletal muscle
weakness. Our current experience in treating early-diagnosed Pompe
patients suggests that treatment initiated before the age of one month
would be most fruitful (manuscript in preparation). Therefore, BNP will be
indispensable in diagnosing HC among newborn babies affected by Pompe
disease, probably as well as among babies affected by other congenital
cardiomyopathies.
Interestingly, the BNP levels in the Pompe newborns seem to be higher
than the levels in the clinically-diagnosed cases that had more advanced
disease and higher LVMI. BNP is synthesized and released by ventricular
myocardial cells in response to myocyte stretch (4). It is possible that
the hemodynamic abnormalities in newborn babies with Pompe disease are
different from the older patients, which leads to the less correlation
between BNP and LVMI. The higher pulmonary resistance in newborns may also
exaggerate the ventricular wall stress in Pompe newborns. Further
researches will be necessary to increase our knowledge about BNP and its
applications.
References
1. Kaski JP, Tome-Esteban MT, Mead-Regan SJ, Pantazis A, Marek J, Deanfield JE, McKenna WJ, Elliott PM B-Type Natriuretic Peptide Predicts Disease Severity in Children With Hypertrophic Cardiomyopathy
Heart 2007.
2. Binder J, Ommen SR, Chen HH, Ackerman MJ, Tajik AJ, Jaffe AS Usefulness of brain natriuretic peptide levels in the clinical evaluation of patients with hypertrophic cardiomyopathy
Am J Cardiol 2007; 100:712-
714.
3. Joyce JJ, Dickson PI, Qi N, Noble JE, Raj JU, Baylen BG Normal right and left ventricular mass development during early infancy
Am J
Cardiol 2004; 93:797-801.
4. de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease
Lancet 2003; 362:316-322.
To the Editor,
In the April 2008 issue of the Journal, Aldous (1) reported the striking case of a young male with Libman-Sacks endocarditis due to primary antiphospholipid syndrome (PAS) A transesophageal echocardiogram performed on the patient revealed a 1.5 X 1.5cm aortic valve vegetation which had apparently embolized to his left lower extremity. A trial of anticoagulation failed to result regression of the...
Dear Editor,
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My interpretation of the provided image would be that the hazy horizontal line which runs through the middle of the aorta most likely represents a typical intimal flap separating a true lumen (lower part) from the false lumen (w...
Dear Editor,
We have read with interest the article of Mascherbauer et al.[1] recently published in Heart and we congratulate our colleagues for an honest effort on shedding some light on an important issue which is still generating some controversy. Nonetheless, based on the title and the conclusions of both the abstract and the paper, we are concerned that the paper may unfortunately convey the wrong message i....
Dear Editor,
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Dear Editor,
Patients with heart failure and a normal left ventricular systolic function correspond to almost half of all patients with congestive heart failure(1). However, the great majority of the data presented in the medical literature are related to studies that observe subjects with heart failure followed by systolic dysfunction. It is notable that Yip et al. (2) in their article assess the quality of l...
Dear Editor,
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Dear Editor,
Patients with heart failure and a normal left ventricular systolic function correspond to almost half of all patients with congestive heart failure(1). However, the great majority of the data presented in medical literature are related to studies that observe subjects with heart failure followed by systolic disfunction. It is notable that Yip et al. (2) in your article assess the quality of life and...
Dear Editor,
Kaski et al. (1) recently reported that in children with hypertrophic cardiomyopathy (HC) the B-type natriuretic peptide (BNP) level correlated with maximal left ventricular (LV) wall thickness and could be a useful tool in assessing disease severity. In adult patients with HC, circulating plasma BNP has been related to the magnitude of heart failure and can be used to detect HC in patients when symp...
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