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.
We have read with interest the recent article by Hippisley Cox et al
on the validation of the new risk estimation function, QRISK. [1] QRISK
demonstrated improved discrimination and calibration compared to
Framingham in the independent British database, THIN. Previously, we wrote
suggesting some methodological limitations in the derivation of the
function. [2] Our main concerns were firstly, the use...
We have read with interest the recent article by Hippisley Cox et al
on the validation of the new risk estimation function, QRISK. [1] QRISK
demonstrated improved discrimination and calibration compared to
Framingham in the independent British database, THIN. Previously, we wrote
suggesting some methodological limitations in the derivation of the
function. [2] Our main concerns were firstly, the use of data in which 70%
had missing values for total cholesterol/HDL cholesterol ratio which were,
su8bsequenrtly imputed and secondly, the use of data from persons on
statin therapy. [3] We believed that the factors were contributing to the
trivial and insignificant hazard ratio associated with TC/HDL ratio in the
original function (0.001 per unit increase in ratio).
Hippisley-Cox et al subsequently published a very satisfactory reply
in which these concerns were confirmed. [4] A new version of the function
excluding those on statin therapy and using an improved multiple
imputation method was derived in which the TC/HDL ratio was a significant
risk factor with a hazard ratio of 1.20 in men and 1.17 in women for CVD
events. This was the version used in the recent validation exercise. In a
further version of the function in which all those with missing data were
excluded, the TC/HDL ratio assumed greater importance again, with hazard
ratios of 1.25 in men and 1.20 in women.
We suggest two possible limitations of the validation exercise. Firstly,
again a large proportion of the dataset had missing data on lipid
measurements (29%). In the case of missing data in the validation cohort
mean values from the derivation cohort, QRESEARCH were substituted. The
authors have not reported whether there were differences in outcomes in
those with missing data. However, substantial differences can be assumed,
given that in the previous cohort the mortality in those with missing data
was substantially higher than that of individuals with complete data.
(10.9% versus 4.9% respectively) Therefore, it is not reasonable to assume
that this group would have the same risk factor levels as those with
complete data in the QRESEARCH database. We suggest that validation of
QRISK in a cohort with more complete data should be undertaken prior to
widespread acceptance of the function.
Secondly, the comparison to the performance of the Framingham
function has been done using the function which was derived in 1991, using
North American data with baselines between in the 1950s and 1970s. [5]
Obviously, important secular trends have occurred during the intervening
years. Therefore, the improvement in calibration of the QRISK function
compared to Framingham may only reflect the use of more recent and local
data, as opposed to an improvement related to the methods or variables
used in QRISK. We suggest that a comparison to a version of Framingham or
SCORE re-calibrated to a modern British population would be more
appropriate. Additionally, while improve in the AUROC is a reasonable
indication of superior discrimination of the model, the percentage of
individuals correctly reclassified to a different risk category using the
new function is particularly clinically relevant, since treatment
decisions are often made based on risk categorisation [6] .
References
1. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Brindle P Performance of the QRISK cardiovascular risk prediction algorithm in an
independent UK sample of patients from a general practice: a validation
study
Heart 2008; 94: 34-49
2. Cooney MT, Dudina AL, Graham IM QRISK – Methodological limitations?
www.bmj.com/cgi/eletters/335/7611/136#172411, accessed Oct 9th 2007
3. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, May M,
Brindle P Derivation and validation of QRISK, a new cardiovascular disease risk
score for the United Kingdom: prospective open cohort study.
BMJ 2007; 335: 136-147
4. Hippisley-Cox J, Coupland C, Vinogradova Y, May M, Brindle P QRISK – authors response
www.bmj.com/cgi/eletters/335/7611/136#174181, accessed Oct 9th 2007
5. Anderson KM, Odell PM, Wilson PW, Kannel WB Cardiovascular disease risk profiles
Am Heart J 1991; 121: 293-8
6. Pencina MJ, D' Agostino RB S, D' Agostino RB J, Vasan RS Evaluating the added predictive ability of a new marker: From area under
the ROC curve to reclassification and beyond.
Stat Med 2008; 27: 207-12
We would like to thank Jaarsma on highlighting an important topic
regarding choosing appropriate outcomes in heart failure research. The
COACH trial recently found that neither moderate or intensive disease
management programmes by a nurse specialising in management of patients
with heart failure reduced death or hospitalisation compared to standard
treatment. (1) In contrast, our trial evaluated...
We would like to thank Jaarsma on highlighting an important topic
regarding choosing appropriate outcomes in heart failure research. The
COACH trial recently found that neither moderate or intensive disease
management programmes by a nurse specialising in management of patients
with heart failure reduced death or hospitalisation compared to standard
treatment. (1) In contrast, our trial evaluated the effectiveness of
improvements in prescribing of evidence based therapies for heart failure
and the appropriate assessment in terms of echocardiography and quality of
life. There are major differences between the two trials. The COACH trial
enrolled patients with heart failure after hospitalisation (1). Most
previously published studies of disease management programmes for patients
with heart failure have recruited patients in a similar way (2). Our
trial was one of the first large intervention trials to have recruited
patients with both confirmed and presumed heart failure from the
community. We chose our outcomes of process, intermediate outcomes of care
and optimisation of diagnosis and medication management because despite
the strong evidence base, patients are still inadequately diagnosed and
managed in primary care (3) We also used an outcome of health related
quality of life as these are important outcomes for patients and they have
been recognised as important clinical indicators which predict use of
health services and mortality in people with chronic heart failure. (4)
Jaarsma mentions that the challenge is to find the most optimal heart
failure management programme in both primary and secondary care. However,
we believe that different models of care and assessment of outcomes will
be required for management of patients who have been discharged after
hospitalisation compared to those who are managed by primary care
physicians. Jaarsma also highlights that the COACH trial used time to
hospitalisation then questions whether this is a good endpoint. This was
illustrated in our cost-effectiveness study when the disease management
programme seemed to lead to increased use of outpatient and inpatient
services. We therefore agree that time to hospitalisation may not be a
good endpoint if appropriate care can lead to referrals for
hospitalisation (5).
References
(1) Jaarsma T, van der Wal MH, Lesman-Leegte I, Luttik ML,
Hogenhuis J, Veeger NJ et al. Effect of moderate or intensive disease
management program on outcome in patients with heart failure: Coordinating
Study Evaluating Outcomes of Advising and Counseling in Heart Failure
(COACH).
Arch Intern Med 2008; 168(3):316-324.
(2) McAlister FA, Lawson FME, Teo KK, et al. Randomised trials
of secondary prevention programmes in coronary heart disease: Systematic
review.
BMJ 2001; 323(7319):957-962.
(3) Strum H, Haaijer-Ruskamp F, Veeger N, Balje-Volkers C, Swedberg K,
van Gilst W. The relevance of comorbidities for heart failure treatment in
primary care: A European survey.
Eur J Heart Fail 2006;8:31-37.
(4) Chin MH, Goldman L. Gender differences in 1-year survival and
quality of life among patients admitted with congestive heart failure.
Med
Care 1998; 36(7):1033-1046.
(5) Turner DA, Paul S, Stone M, Juarez-Garcia A, Squire I, Khunti K. The cost-effectiveness a disease management programme for secondary
prevention of
coronary heart disease and heart failure in primary care.
Heart (in press)
I read with great interest the article presenting tissue Doppler
techniques as technological advances.[1] The authors conclude with the
“limitations” of tissue Doppler stating “There is still a significant
variability in TDI (tissue Doppler imaging) derived parameters because of
differences in machine characteristics and lack of guidelines for
standardization of sample positions and machine setting...
I read with great interest the article presenting tissue Doppler
techniques as technological advances.[1] The authors conclude with the
“limitations” of tissue Doppler stating “There is still a significant
variability in TDI (tissue Doppler imaging) derived parameters because of
differences in machine characteristics and lack of guidelines for
standardization of sample positions and machine settings. Therefore it is
still difficult to provide firm recommendations for clinical practice.
More clinical trials are needed for establishing sensitive and effective
parameters for diagnosing specific conditions or detecting abnormalities”.
In which case is it technological advances?
There are philosophical, methodical and application flaws in tissue
Doppler.[2] The basic principles of measurement and Doppler are
compromised in this technique. After you make a measurement as per
established methods you could have “limitations”. But if you make a
measurement paying scant regard to established norms it’s a “blunder”. So
you cannot blame “differences in machine characteristics” nor “lack of
guidelines for standardization of sample positions and machine settings”.
It is like measuring the height of a patient without knowing the required
alignment, making random measurements and calling the erroneous
measurements as “limitations” of the scale (see figure)! This would be a
case of right tool, wrongly used. You cannot sweep the basic flaws under
the carpet by labeling them as “limitations”.
The authors state “In practice, from the apical window, only
longitudinal shortening can be obtained from every segment of the left and
right ventricle. These longitudinal velocities reflect both active and
passive myocardial motion, which forms the major limitation of the
technique”. The problem here is much more than “active and passive
myocardial motion”. Doppler will give consistent results only if there is
a unique velocity or if the other conflicting velocity vectors are
constant. In tissue motion there are several velocity vectors affecting
the resultant longitudinal vector. Since we do not know the influence of
these conflicting vectors we will consistently get variable results.
Compare flow motion and tissue motion to understand this better.
The authors also state that “The sample volume should be positioned
in the centre of the region of interest. It is recommended to check the
sample volume position before acquiring the still frames since the motion
of the atrioventricular ring may differ around the basal myocardial
segment”. Pray, where are the regions of interest and the points of
interrogation? In case of flow Doppler these are unique points - the
normal and abnormal orifices. Can we ever define a proper point of
interrogation on tissue Doppler? That is also why the authors correctly
state “normal values for longitudinal velocities depend on the position of
the sample area within the wall”. This is also why, as the authors
mention, there are “lack of guidelines for standardization of sample
positions”.
Doppler strain and E/E’ are incorrect because the foundation is
wrong. Besides in the formula for strain calculation, the modulus of a
vector quantity (velocity) is incorrectly substituted for a scalar
quantity (length) in the original equation. E/E’ also goes against the
scientific “principle of parsimony”.[3]
When cardiac uses of Doppler were first studied, Doppler recordings
were thought to come from the heart tissues and no signals were attributed
to blood flow. Consequently the Doppler technique did not interest the
cardiologists then! When considering developments in echocardiography, the
developments should incrementally add to our knowledge and refine the data
collection. In tissue Doppler it is a retrograde development. We use
Doppler to study flow because we cannot image flow. When imaging flow
becomes a reality, Doppler would be relegated to the background. When we
can “see” the tissue there is no need for an indirect Doppler methodology.
In this context the authors mention about 2D speckle tracking. They state
“Local 2-dimensional tissue velocity vectors are derived from the spatial
and temporal data of each speckle” This would be advancement in the right
direction.
Another problem is the high sensitivity of tissue Doppler
compromising on the specificity. An akinetic segment correctly displayed
on M-mode is never displayed as 0 velocity on tissue Doppler. This will
also affect the temporal data. The authors correctly mention this albeit
with a wrong explanation. “However, in patients with ischemic
cardiomyopathy, TDI and realtime three-dimensional echocardiography show
poor agreement for evaluating the magnitude of intraventricular
dyssynchrony and the site of maximal mechanical delay. This may be
explained by their respective assessment of longitudinal versus radial
timing”.
Tissue Doppler can never be a technological advancement. All
advancements are built on strong foundations in basic sciences. Here the
basic principles of measurement and Doppler are compromised. Making
clinical judgments based on this faulty modality would be unacceptable to
the scientific cardiologist.
Figure 1
Principles of measurement. We should know the alignment before we apply the measurement tool. In the case of measurement of height, the person has to be standing erect and the scale has to be applied in the AB direction. Any other measurement like XY would be invalid. Similarly you cannot measure the height correctly in a non-erect position. In tissue Doppler measurements we do not know the alignment of the significant velocity vector to apply the Doppler tool. Besides, myocardial motion is complex and cannot be studied with "line of sight" measurement tool like Doppler.
References
1. Van de Veire N, De Sutter J, Bax JJ, and Roelandt JR. Technological advances tissue doppler imaging echocardiography
Heart
Online First. January 29, 2008
2. Thomas G. Tissue Doppler echocardiography – A case of right tool,
wrong use.
Cardiovascular Ultrasound 2004;2:12.
Available at
http://www.cardiovascularultrasound.com/content/2/1/12
3. Thomas G. Is E/E’ really reliable? Comment on
Cardiovascular
Ultrasound 2007; 5:16.
Available at
http://www.cardiovascularultrasound.com/content/5/1/16/comments
With great interest I read the "Images in cardiology" article by
Boussuges et al. (1) showing circulating bubbles in the right and the left
cavities of a scuba diver's heart after diving. The authors stress the
importance of a patent foramen ovale (PFO) as a possible right to left
shunting mechanism. However, there are other mechanisms for right to left
shunting of intravenous bubbles in scuba diver...
With great interest I read the "Images in cardiology" article by
Boussuges et al. (1) showing circulating bubbles in the right and the left
cavities of a scuba diver's heart after diving. The authors stress the
importance of a patent foramen ovale (PFO) as a possible right to left
shunting mechanism. However, there are other mechanisms for right to left
shunting of intravenous bubbles in scuba divers, e.g. exercise (2).
Indeed, post-diving arterial bubbles have been detected in scuba divers
who did not have a PFO (3).
Thus, it should be emphasised that it is not the presence of the PFO per
se that causes the problem but the level of venous circulating bubbles.
Scuba divers in general should be cautioned to adhere to safe dive
profiles in order to avoid any disastrous consequences of shunting
bubbles.
References
1. Boussuges A, Blatteau JE, Pontier JM. Bubbles in the left cardiac cavities after diving. Heart 2008;94:445
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I read with great interest the article presenting tissue Doppler techniques as technological advances.[1] The authors conclude with the “limitations” of tissue Doppler stating “There is still a significant variability in TDI (tissue Doppler imaging) derived parameters because of differences in machine characteristics and lack of guidelines for standardization of sample positions and machine setting...
Dear Editor,
With great interest I read the "Images in cardiology" article by Boussuges et al. (1) showing circulating bubbles in the right and the left cavities of a scuba diver's heart after diving. The authors stress the importance of a patent foramen ovale (PFO) as a possible right to left shunting mechanism. However, there are other mechanisms for right to left shunting of intravenous bubbles in scuba diver...
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