The editorial accompanying our paper on age, sex, and sudden death
questions the high mortality in consecutive patients after an acute
myocardial infarction (MI). The mortality we describe is high compared to
the patients randomised in various studies, but it is comparable to the
mortality found in other surveys.
The Minnesota Heart Survey[1] describes
the mortality of unselected patients be...
The editorial accompanying our paper on age, sex, and sudden death
questions the high mortality in consecutive patients after an acute
myocardial infarction (MI). The mortality we describe is high compared to
the patients randomised in various studies, but it is comparable to the
mortality found in other surveys.
The Minnesota Heart Survey[1] describes
the mortality of unselected patients below 75 years of age – and the
mortality is identical to patients younger than 75 years from the cohort
that we studied. The comparison with the mortality in a number of
randomised studies is not relevant. It is well known that randomised
patients are not typical patients and we have demonstrated the dramatic
effect of the selection procedure for a trial on the mortality eventually
found [2] in the randomised patients.
To further emphasize that the mortality we describe is abnormal our data
are compared with the Framingham Heart Study [3] in which the age-adjusted
annual rate of sudden death for men with a previous myocardial infarction
is 1.75%. This comparison is also not relevant because the mortality we
describe is during the initial 2-4 years after the acute event, whereas
the Framingham study describes mean event rates during 38 years – and the
event rates after a myocardial infarction are far from constant.
Worthwhile studies can be made from many sources of data, including data
from randomised studies. However, it should always be kept in mind that
patients in randomised studies are highly selected and not representative
of the main selection criteria. A genuine high risk in such populations
is extremely rare. Therefore, studies on unselected populations such as
the one we have performed are important to ensure that findings from more
selected populations can be extrapolated to the findings in society.
References
(1) McGovern PG, Pankow JS, Shahar E, Doliszny KM, Folsom AR,
Blackburn H et al. Recent trends in acute coronary heart disease--
mortality, morbidity, medical care, and risk factors. The Minnesota Heart
Survey Investigators. N Engl J Med 1996;334:884-90.
(2) Køber L, Torp-Pedersen C. Clinical characteristics and mortality of patients screened for entry into the Trandolapril Cardiac Evaluation
(TRACE) study. Am J Cardiol 1995;76:1-5.
(3) Kannel WB, Wilson PW, D'Agostino RB, Cobb J. Sudden coronary death in
women. Am Heart J 1998;136:205-12.
Fruhwald FM and their colleagues mentioned about ANP synthesis from
the atrium in their lecture.
Most of the ANP is synthesized in the myocites of atrium and the synthesis
is prominent in the right atrium than the left. Another location of the
ANP synthesis is the ventricles. The highest ANP expression is in the
intrauterine period, it declines after birth and reaches to the adult
levels of 1-2% of atriu...
Fruhwald FM and their colleagues mentioned about ANP synthesis from
the atrium in their lecture.
Most of the ANP is synthesized in the myocites of atrium and the synthesis
is prominent in the right atrium than the left. Another location of the
ANP synthesis is the ventricles. The highest ANP expression is in the
intrauterine period, it declines after birth and reaches to the adult
levels of 1-2% of atrium.[1] Ventricular expression increases with volume
overload,increased pressure or both.[2] Also, it has been shown that, ANP
can be released from the ventriculs in dilated cardiomyopathy as
well.[3] As the heart failure progresses, the atrial ANP synthesis and the
gene expression decreases, but the expression continous from the ventricle.[4]
BNP has been mentioned another good predictor of heart failure in the
literature. However, Wei et al, reported that, the plasma levels of BNP
remains the same in the early stages of heart failure.[6] Therefore, in
this study ANP has been decleared by early predictor of heart failure in
the asymptomatic stage.
(3) Yasue H, Obata K, Okumura K, Kurose M, Ogawa H, Matsuyama K, Jougasaki
M: Increased secretion of atrial natriuretic polypeptide from the left
ventricule in patients with dilated cardiomyopathy. J Clin Invest 1989;83:46-51.
(4) Satio Y, Nakao K, Nishimura K, Sugawara A, Okumura K, Obata K: Clinical
application of atrial natriuretic polypeptide in patients with congestive
heart failure: Beneficial effects on left ventricular function.
Circulation 1987;76:115-124.
(5) Yoshimura M, Yasue H, Okumura K, Ogawa H, Jougasaki M, Mukoyama M:
Different secretion patterns of atrial natriuretic peptide and brain
natriuretic peptide in patients with congestive heart failure. Circulation 1993;
87:464-469.
(6) Wei CM, Heublein DM, Perrella MA, Lerman A, Rodeheffer RJ, Mc Gregor
CGA, Edwards WD: Natriuretic peptide system in human heart failure.
Circulation 1993;88:1004-9.
We appreciated the comments of Dr Guntheroth et al. We specifically
chose to eliminate patent foramen ovale from our study, hence patients
with a defect...
We appreciated the comments of Dr Guntheroth et al. We specifically
chose to eliminate patent foramen ovale from our study, hence patients
with a defect <_3mm were="were" excluded="excluded" from="from" inclusion.="inclusion." dr="dr" gunteroth="gunteroth" raises="raises" an="an" interesting="interesting" point="point" that="that" some="some" of="of" the="the" small="small" asds="asds" which="which" we="we" described="described" as="as" undergoing="undergoing" spontaneous="spontaneous" closure="closure" particularly="particularly" those="those" measuring="measuring" approximately="approximately" _3-4mm="_3-4mm" may="may" have="have" in="in" fact="fact" represented="represented" stretched="stretched" patent="patent" foramen="foramen" ovale="ovale" if="if" infant="infant" was="was" young="young" and="and" had="had" a="a" recent="recent" arterial="arterial" duct="duct" with="with" left="left" atrial="atrial" enlargement.="enlargement." cases="cases" underwent="underwent" diagnosed="diagnosed" all="all" children="children" greater="greater" than="than" _1="_1" year="year" age="age" no="no" case="case" there="there" prominent="prominent" septal="septal" flap="flap" to="to" raise="raise" suspicion="suspicion" pfo.="pfo." p="p"/>
Likewise, all these children had a left-to-right shunt
via the defect which given such considerations resulted in our calling
them small ASDs. Whether some of these represented stretched PFO is
however quite difficult to refute emphatically. The question does however
raise the interesting point of where the cut-off point is between a
stretched PFO and a small ASD when solely using echocardiography to make
this judgement? Irrespective of this point however our study set out to
determine how many ASDs outgrew the potential for transcatheter closure
using the specific device we had available at our institution at the time.
In the March issue of Heart, McMahon and colleagues
presented an excellent review of this subject.[1] I have one question for the
authors. You describe four patients with small ASDs that had spontaneous
closure of the defect. Since the method for spontaneous closure for
ventricular septal defects, by consensus, is roughening of the endocardium
of the rim of the defect by the high velocity of the jet,...
In the March issue of Heart, McMahon and colleagues
presented an excellent review of this subject.[1] I have one question for the
authors. You describe four patients with small ASDs that had spontaneous
closure of the defect. Since the method for spontaneous closure for
ventricular septal defects, by consensus, is roughening of the endocardium
of the rim of the defect by the high velocity of the jet, but the velocity
across most ASDs is less than 1 m/s, it is difficult to think that an ASD
would ever close from that means. Isn't it likely that these were simply
foramen ovale that were stretched by enlargement of the left atrium due to
ductal flow as an infant that has closed, leaving the incompetent foramen
ovale to gradually regress as the enlargement disappeared. We found that
this was a frequent occurrence in the premature infant population (Zhou and Guntheroth).[2]
References
(1) C J McMahon, T F Feltes, J K Fraley, J T Bricker, R G Grifka, T A Tortoriello, R Blake, and L I Bezold. Natural history of growth of secundum atrial septal defects and implications for transcatheter closure. Heart 2002; 87:256-259.
(2) Zhou TF, Guntheroth WG. Valve-incompetent foramen ovale in premature infants
with ductus arteriosus. JACC 1987;10:193-9
In writing our editorial,[1] we were well aware of the HOPE
substudy,[2] reported in the journal ‘Hypertension’, which described the
results of ambulatory blood pressure monitoring in 38 patients with
peripheral vascular disease. The substudy found that, compared with
placebo, ramipril treatment produced a significant reduction in ambulatory
blood pressure (10/4 mm Hg, p = 0.03) and a non-significant...
In writing our editorial,[1] we were well aware of the HOPE
substudy,[2] reported in the journal ‘Hypertension’, which described the
results of ambulatory blood pressure monitoring in 38 patients with
peripheral vascular disease. The substudy found that, compared with
placebo, ramipril treatment produced a significant reduction in ambulatory
blood pressure (10/4 mm Hg, p = 0.03) and a non-significant reduction in
office blood pressure (8/2 mm Hg, p = NS).
There were important differences between this small substudy cohort
and the overall HOPE study population, including a higher incidence of
peripheral vascular disease (100% versus 19%), higher office blood
pressure at baseline (151/81 mm Hg versus 139/79 mm Hg) and older age (71
years versus 66 years).
Whether the benefit of ramipril in the HOPE study was due largely to
blood pressure lowering or to other effects was not the focus of our
editorial. This issue has been discussed recently by the authors of the
HOPE study in ‘The Lancet’.[3] Instead, our editorial highlighted the
importance of assiduous blood pressure control after acute coronary events
and the rationale for the use of an ACE inhibitor.
We agree that clinicians need to consider all relevant information
when attempting to integrate findings from trials into clinical practice.
References
(1) Wong CK, White HD. Relation between blood pressure after an acute
coronary event and subsequent cardiovascular risk [editorial]. Heart
2002;88:555-8.
(2) Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J.
Comparative effects of ramipril on ambulatory and office blood pressures:
a HOPE substudy. Hypertension 2001;38:e28-e32.
(3) Sleight P, Pogue J, Yusuf S. Blood pressure and cardiovascular
risk in the HOPE study [letter]. Lancet 2002;359:2117-8.
Wong and White are responsible for perpetuating inaccuracies in their
article. Unfortunately, the ambulatory BP data on the HOPE trial was not
published in the NEJM, but in a more obscure hypertension journal, but
even the authors conceded that blood pressure reduction in the HOPE trial
played a major role that was not "initially appreciated". The BP
differences between the two groups were staggering, exp...
Wong and White are responsible for perpetuating inaccuracies in their
article. Unfortunately, the ambulatory BP data on the HOPE trial was not
published in the NEJM, but in a more obscure hypertension journal, but
even the authors conceded that blood pressure reduction in the HOPE trial
played a major role that was not "initially appreciated". The BP
differences between the two groups were staggering, explained in part by the
giving of ramipril at night in the trial. Wong and White nearly got it
right when they noticed the blood pressure differences between the QUIET
and the HOPE trials, but did not conclude that it is reduction in blood
pressure that counts.
The HOPE trial was the first hypertension trial that analysed blood
pressure lowering in a high risk group of "so-called" normotensives. To
imply anything else about the trial is pure conjecture and unfortunately
exposes the pharmaceutical industry's desire to niche a drug.
People writing reviews should analyse each paper quoted independently,
before sprouting the "common wisdom".
Dr Otterstad makes some incisive points about the reproducibility of
left ventricular volumes and ejection fractions. In general, it is
remarkable how silly we are from a quantitative point of view, when we
plan research. We make extensive arrangements to design a study, consent
subjects, transport them to hospital, arrange them on an echo table, set
up our machinery, measure our variable of interest jus...
Dr Otterstad makes some incisive points about the reproducibility of
left ventricular volumes and ejection fractions. In general, it is
remarkable how silly we are from a quantitative point of view, when we
plan research. We make extensive arrangements to design a study, consent
subjects, transport them to hospital, arrange them on an echo table, set
up our machinery, measure our variable of interest just once, and then do
all the previous steps in reverse. The only scientifically valuable step
is the measurement of the variable with as little random error as
possible, yet (usually) we spend no time on minimising this error.
The consequences are not only the problem that Dr Otterstad points
out, but also failure of the measured variable to show its true
correlation with any other variable.[1]
There are many strategies we can take to minimise random error, but
the only universally effective technique is to measure the variable more
than once and take the average. As a (remarkable) consequence of the
central limits theorem of statistics, regardless of the distribution of
the measurements we make (i.e. even if they are skewed), the mean of
several measurements takes on a normal distribution whose standard
deviation falls with the square root of the number of measurements we have
meaned.
Thus measuring left ventricular volumes 4 times (i.e. from 4 separate
echo recordings), rather than once, and then taking the mean, may be
expected to halve the reproducibility range. Our instincts may be to laugh
at the prospect of repeating the study so many times, but actually it is
probably the most effective use of the time of staff and patients. It only
seems time-wasting if one ignores the consequences of a study whose
reproducibility is twice as wide -- four times as many patients are
needed!
Which is more wasteful - quadrupling the scanning time or quadrupling
the study size overall?
Darrel Francis
Specialist Registrar in Cardiology
St Mary's Hospital
Reference
(1) Francis DP, Gibson DG, Coats AJS. How high can a correlation
coefficient be? Effects of limited reproducibility of common cardiological
measures. Int J Cardiol 1999, 65:185-189.
I am surprised that an educational paper about cardiovascular risk in
hypertension did not mention the paper by Pocock et al.[1] Not only
were more than 47 000 patients used to derive the score but 20 000 of them
had participated in UK-based trials.
In the last year, I have found it much easier to explain to patients
the 'Pocock' score than I ever did when I was using th...
I am surprised that an educational paper about cardiovascular risk in
hypertension did not mention the paper by Pocock et al.[1] Not only
were more than 47 000 patients used to derive the score but 20 000 of them
had participated in UK-based trials.
In the last year, I have found it much easier to explain to patients
the 'Pocock' score than I ever did when I was using the Framingham score.
Reference
(1) Pocock SJ, McCormack V, Gueyffier F, Boutitie F, Fagard RH, and Boissel J-P. A score for predicting risk of death from cardiovascular disease in adults with raised blood pressure, based on individual patient data from randomised controlled trials BMJ 2001;323:75-81. and http://www.riskscore.org.uk
The role of inflammation mechanisms in the pathogenesis and
progression of coronary artery disease (CAD) has been increasingly
discussed, but still remains unclear.
Seroepidemiological studies have suggested an association between atherosclerosis and chronic infection,
with most of the published studies referring to Chlamydia pneumoniae (Cpn)
Helicobacter pylori (Hp).[1-4]
The role of inflammation mechanisms in the pathogenesis and
progression of coronary artery disease (CAD) has been increasingly
discussed, but still remains unclear.
Seroepidemiological studies have suggested an association between atherosclerosis and chronic infection,
with most of the published studies referring to Chlamydia pneumoniae (Cpn)
Helicobacter pylori (Hp).[1-4]
The study von Sigh (Prospective analysis of the association of infection
with CagA bearing strains of Helicobacter pylori and coronary heart
disease“ Heart 2002;88: 43-46] showed an association between serological
status and development of atherosclerosis.[5]
Recently we published our data[6] with direct proof of Hp-DNA by PCR and
nucleotide sequence analysis in atherosclerotic coronary arteries. The
detection of Hp DNA but not serological findings was strongly associated
with clinical symptoms such as unstable angina and myocardial infarction.
In conclusion, the detection of Hp specific DNA in atheromatous plaque
material from coronary arteries and the strong association to the clinical
symptom of unstable angina could be interpreted as a direct involvement of
a Hp infection to the progression of pre-existent or concurrent CAD
induced by a local inflammatory process and subsequent local vascular
thrombosis. Similar to the gastric epithelial destruction Hp may cause a
direct endothelial damage of the arterial wall with subsequent plaque
instability by its toxic substances including proinflammatory cytokines
inclusive CagA cytotoxins, endotoxins, and others.
References
(1) Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH,
Huttunen JK, Valtonen V. Serological evidence of an association of a novel
Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial
infarction. Lancet 1988;2:983-986.
(2) Glynn J. Helicobacter pylori and the heart. Lancet 1994;344:146.
(3) Gunn M, Stephens JC, Thompson JR, Rathbone BJ, Samani NJ. Significant
association of cagA positive Helicobacter pylori strains with risk of
premature myocardial infarction. Heart 2000;84:267-271
(4) Kowalski M, Konturek PC, Pieniazek P et al. Prevalence of Helicobacter
pylori infection in coronary artery disease and effect of its eradication
on coronary lumen reduction after percutaneous coronary angioplasty.
Digest Liver Dis 2001;3: 222-229.
(5) Singh RK, McMahon AD, Patel H, Packard CJ, Rathbone BJ, Samani NJ for
the West of Scotland Coronary Prevention Group: Prospective analysis of
the association of infection with CagA bearing strains of Helicobacter
pylori and coronary heart disease. Heart 2002; 88: 43-46
(6) Kowalski M, Rees W, Konturek PC, Grove R, Scheffold T, Maixner H,
Brunec M, Franz N, Konturek JW, Pieniazek P, Hahn EG, Konturek SJ, Thale
J, Warnecke H: Association of Helicobacter pylori specific DNA in human
atheromatous coronary arteries to prior myocardial infarction and unstable
angina. Digest Liver Dis 2002;34:398-402.
We write to report that over the last 8 months we have used
intravenous Midazolam for DC cardioversion and have not experienced the
potential problems of excess or under sedation described by SJ Harrison
and J Mayet.[1]
Between 11.12.2001 and 9.8.2002, 236 patients have undergone
cardioversion using intravenous Midazolam with a mean dose of 7 mg(+/-
5.04 mg). 227(96.18 %) were successfully cardi...
We write to report that over the last 8 months we have used
intravenous Midazolam for DC cardioversion and have not experienced the
potential problems of excess or under sedation described by SJ Harrison
and J Mayet.[1]
Between 11.12.2001 and 9.8.2002, 236 patients have undergone
cardioversion using intravenous Midazolam with a mean dose of 7 mg(+/-
5.04 mg). 227(96.18 %) were successfully cardioverted at a mean energy of
shock of 75J(+/-42.25 J) from a biphasic defibrillator. All patients
received 200 mcg of Flumazenil after cardioversion. There were no
respiratory arrests. Five patients had brief periods of bradycardia and 2
required intravenous Atropine. One patient needed 16 mg of Midazolam and
another patient in whom 12 mg of midazolam was not successful, needed to
be anaesthetised. For the first 4 months an Anaesthetist was present
throughout the procedure but is now available on standby. The patients
have been audited for their recall of the procedure. Only 22 (9.3 %) could
remember the shock (shocks) and only 2 found them unpleasant.
The opportunity was taken to look again at the whole cardioversion
service which had been rather disorganised, and was mainly operated by
SHOs who often found conflicts of interest for their time. All patients
are now seen in a Cardioversion Clinic, 1 week before the procedure. The
appropriateness of cardioversion, a check of the previous tests (renal
function tests, liver function tests, echocardiogram, thyroid function,
INR and consent) are obtained. A Hospital Specialist supervises the
cardioversion with a nurse and a physiological measurement technician . At
the start of the programme a Consultant was present too. All patients
return one week and one month later for repeat ECG. Eight to ten elective
patients are now cardioverted in a 3½ hour session. The same protocol has
been used for a small number of non-elective cardioversions.
Cardioversion patients are monitored both for their ECG and oxygen
saturations. The same is true for patients undergoing transoesophageal
echocardiograms and automatic cardioversion defibrillator testing.
We will continue to audit this reorganised cardioversion procedure,
but we have found intravenous Midazolam sedation to be safe and
satisfactory for DC cardioversion.
Reference
(1) Harrison SJ and Mayet J. Physician administered sedation for DC cardioversion. Heart 2002;88:117-118 .
Dear Editor
The editorial accompanying our paper on age, sex, and sudden death questions the high mortality in consecutive patients after an acute myocardial infarction (MI). The mortality we describe is high compared to the patients randomised in various studies, but it is comparable to the mortality found in other surveys.
The Minnesota Heart Survey[1] describes the mortality of unselected patients be...
Dear Editor
Fruhwald FM and their colleagues mentioned about ANP synthesis from the atrium in their lecture. Most of the ANP is synthesized in the myocites of atrium and the synthesis is prominent in the right atrium than the left. Another location of the ANP synthesis is the ventricles. The highest ANP expression is in the intrauterine period, it declines after birth and reaches to the adult levels of 1-2% of atriu...
Dear Editor
We appreciated the comments of Dr Guntheroth et al. We specifically chose to eliminate patent foramen ovale from our study, hence patients with a defect...
Dear Editor
In the March issue of Heart, McMahon and colleagues presented an excellent review of this subject.[1] I have one question for the authors. You describe four patients with small ASDs that had spontaneous closure of the defect. Since the method for spontaneous closure for ventricular septal defects, by consensus, is roughening of the endocardium of the rim of the defect by the high velocity of the jet,...
Dear Editor
In writing our editorial,[1] we were well aware of the HOPE substudy,[2] reported in the journal ‘Hypertension’, which described the results of ambulatory blood pressure monitoring in 38 patients with peripheral vascular disease. The substudy found that, compared with placebo, ramipril treatment produced a significant reduction in ambulatory blood pressure (10/4 mm Hg, p = 0.03) and a non-significant...
Dear Editor
Wong and White are responsible for perpetuating inaccuracies in their article. Unfortunately, the ambulatory BP data on the HOPE trial was not published in the NEJM, but in a more obscure hypertension journal, but even the authors conceded that blood pressure reduction in the HOPE trial played a major role that was not "initially appreciated". The BP differences between the two groups were staggering, exp...
Dear Editor
Dr Otterstad makes some incisive points about the reproducibility of left ventricular volumes and ejection fractions. In general, it is remarkable how silly we are from a quantitative point of view, when we plan research. We make extensive arrangements to design a study, consent subjects, transport them to hospital, arrange them on an echo table, set up our machinery, measure our variable of interest jus...
Dear Editor
I am surprised that an educational paper about cardiovascular risk in hypertension did not mention the paper by Pocock et al.[1] Not only were more than 47 000 patients used to derive the score but
20 000 of them had participated in UK-based trials.
In the last year, I have found it much easier to explain to patients the 'Pocock' score than I ever did when I was using th...
Dear Editor
The role of inflammation mechanisms in the pathogenesis and progression of coronary artery disease (CAD) has been increasingly discussed, but still remains unclear.
Seroepidemiological studies have suggested an association between atherosclerosis and chronic infection, with most of the published studies referring to Chlamydia pneumoniae (Cpn) Helicobacter pylori (Hp).[1-4]
T...
Dear Editor
We write to report that over the last 8 months we have used intravenous Midazolam for DC cardioversion and have not experienced the potential problems of excess or under sedation described by SJ Harrison and J Mayet.[1]
Between 11.12.2001 and 9.8.2002, 236 patients have undergone cardioversion using intravenous Midazolam with a mean dose of 7 mg(+/- 5.04 mg). 227(96.18 %) were successfully cardi...
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