We thank Corea F et al. for highlighting the inconsistency between
the current clinical practice and guidelines in the use of oral
anticoagulation for stroke prevention in patients with atrial fibrillation
(AF). The purpose of our study was to determine the clinical implication
of transient and non-sustained atrial arrhythmias detected by the
pacemaker [1]. Our findings suggest that device detected...
We thank Corea F et al. for highlighting the inconsistency between
the current clinical practice and guidelines in the use of oral
anticoagulation for stroke prevention in patients with atrial fibrillation
(AF). The purpose of our study was to determine the clinical implication
of transient and non-sustained atrial arrhythmias detected by the
pacemaker [1]. Our findings suggest that device detected atrial
arrhythmias was associated with a 1.5 fold increase in major
cardiovascular event, especially stroke.
In this retrospective analysis, the reasons for under-utilization of
anticoagulation in patients with AF could not be clearly determined.
However, there are several potential explanations for a relatively low
percentage of our Chinese AF patients treated with anticoagulation at
baseline and during follow-up. First, current guidelines [2, 3] have not
specifically addressed the use of anticoagulation based on device detected
transient atrial arrhythmias. However, based on our data [1] and recent
studies by Glotzer TV et al. [4], the presence of device detected AF
episodes, irrespectively of symptoms, was associated with an increase risk
of stroke. Anticoagulation therapy should be considered in those high risk
patients with AF detected by the implantable device. The future
application of wireless remote monitoring for atrial arrhythmias using
implantable device may further enhance early detection of AF for the use
of anticoagulation in high risk patients [5]. Second, most of the current
data regarding the use of anticoagulation for prevention of
thromboembolism in AF are on Caucasians population (97%) [2, 3].
Furthermore, Chinese population has a higher prevalence of hemorrhagic
stroke than Caucasians population [6]. As a result, the safety and
efficacy of anticoagulation therapy for prevention of thromboembolic event
in Chinese population remain unclear. Lastly, the utilization of
anticoagulation in Chinese population is further confounded by the lower
dose requirement [7] and a high prevalence of herbal intake [8].
Therefore, more studies are needed to evaluate the optimal use of
anticoagulation for stroke prevention in Chinese patients with AF.
References:
1. Tse HF, Lau CP. Prevalence and clinical implications of atrial
fibrillation episodes detected by pacemaker in patients with sick sinus
syndrome. Heart. 2005;91:362-4.
2. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for
the management of patients with atrial fibrillation: executive summary; a
report of the American College of Cardiology/American Heart Association
Task Force on Practice Guidelines and the European Society of Cardiology
Committee for Practice Guidelines and Policy Conferences (Committee to
Develop Guidelines for the Management of Patients With Atrial
Fibrillation) developed in collaboration with the North American Society
of Pacing and Electrophysiology. Circulation 2001;104,2118-2150.
3. Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ.
Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference
on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:429S-456S.
4. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak
R, Cook J, Paraschos A, Love J, Radoslovich G, Lee KL, Lamas GA; MOST
Investigators. Atrial high rate episodes detected by pacemaker diagnostics
predict death and stroke: report of the Atrial Diagnostics Ancillary Study
of the MOde Selection Trial (MOST). Circulation. 2003;107:1614-9.
6. Ayala C, Croft JB, Greenlund KJ, Keenan NL, Donehoo RS, Malarcher
AM, Mensah GA. Sex differences in US mortality rates for stroke and stroke
subtypes by race/ethnicity and age, 1995-1998. Stroke. 2002;33:1197-201.
7. Gan GG, Teh A, Goh KY, Chong HT, Pang KW. Racial background is a
determinant factor in the maintenance dosage of warfarin. Int J Hematol.
2003;78:84-6.
8. Wong RS, Cheng G, Chan TY. Use of herbal medicines by patients
receiving warfarin. Drug Saf. 2003;26:585-8.
Saliba and colleagues are to be congratulated on their study to establish the quality of life in the setting of complex congenital cardiac malformations. My comments are in no way intended as a criticism of their excellent and much-needed investigation. It is depressing, however, to
note that anatomical description lags so far behind the sophisticated evaluation of status of health. It is very likely that none of the patien...
Saliba and colleagues are to be congratulated on their study to establish the quality of life in the setting of complex congenital cardiac malformations. My comments are in no way intended as a criticism of their excellent and much-needed investigation. It is depressing, however, to
note that anatomical description lags so far behind the sophisticated evaluation of status of health. It is very likely that none of the patients studied possessed an anatomically univentricular heart. Indeed, the criterion for inclusion was "complex congenital heart disease in which
a biventricular repair can never be achieved". These patients have a functionally univentricular circulation, but the anatomic features unifying the group is presence of one big and one small ventricle. Can we not aspire to describe such patients in terms which even they themselves
might understand?
We have read with interest the article by Takeda et al.[1]. Our group has previously observed that patients with aortic stenosis often have selective decreases in ventricular longitudinal shortening and wall thickening concomitant with normal fractional shortening and ejection
fraction [2-4]. In the same studies, we also postulated that since subendocardial fibres are oriented longitudinally, this selective dec...
We have read with interest the article by Takeda et al.[1]. Our group has previously observed that patients with aortic stenosis often have selective decreases in ventricular longitudinal shortening and wall thickening concomitant with normal fractional shortening and ejection
fraction [2-4]. In the same studies, we also postulated that since subendocardial fibres are oriented longitudinally, this selective decrease in longitudinal shortening may be the result of an increase in subendocardial wall stress and the associated subendocardial abnormalities that are often observed in patients with aortic stenosis. Moreover, the potential interest of longitudinal shortening in patients with aortic
stenosis is also confirmed by our recent observation [5] that the main change in left ventricular function occurring after aortic valve replacement is a selective improvement of the left ventricular longitudinal shortening. These previously reported data are thus highly consistent with the data of Takeda et al and we fully agree with their interpretation that these observations are likely due to changes in subendocardial myocardial function. In this context, the relation they found between long axis excursion and symptoms is particularly interesting and coherent.
On the other hand, Takeda et al measured the absolute change in longitudinal shortening using M-mode echocardiography whereas we have evaluated relative longitudinal shortening using M-mode echocardiography
and a validated mathematical model of the dynamic geometry of the left ventricle. We would like to submit that relative shortening is probably more sensitive to intrinsic changes in function since absolute shortening is also influenced by the size of the ventricle, irrespective of function. For the same reason, it could also better correlate with the appearance of symptoms but this remains to be demonstrated. From a practical standpoint, it should also be emphasized that newer methods such as analysis of strain using Doppler tissue imaging [6] will probably render the evaluation of relative left ventricular longitudinal shortening much easier compared to the M-mode method. The use of the latter in the context of aortic stenosis however needs to be validated.
References
(1). Takeda S, Rimington H, Smeeton N, Chambers J. Long axis excursion in aortic stenosis. Heart 2001;86(1):52-6
(2). Dumesnil J G, Shoucri R M, Laurenceau J L, Turcot J. A mathematical model of the dynamic geometry of the intact left ventricle and its application to clinical data. Circulation 1979;59(5):1024-34.
(3). Dumesnil J G, Shoucri R M. Effect of the geometry of the left ventricle on the calculation of ejection fraction. Circulation 1982;65(1):91-8.
(4). Dumesnil J G, Shoucri R M. Quantitative relationships between left ventricular ejection and wall thickening and geometry. J Appl Physiol 1991;70(1):48-54.
(5). Pibarot P, Dumesnil J G, LeBlanc M H, Cartier P, Métras J. Changes in left ventricular mass and function after aortic valve replacement: A comparison between stentless and stented bioprosthetic valves.
J Am Soc Echocardiogr 1999;12(11):981-7.
(6). Voigt J-U, Arnold M F, Karlsson M, Hübbert L, Kukulski T, Hatle L, Sutherland G R. Assessment of regional longitudinal myocardial stain rate derived from Doppler myocardial imaging indexes in normal and infarcted
myocardium. J Am Soc Echocardiogr 2000;13:588-98.
The activity monitoring analysis of the UK-HEART study published by
Gall et al. [1] is very welcome. They calculate that screening of 551
ambulant patients with stable heart failure according to NICE guidance [2]
would result in 142 electrophysiology studies (EPS) and the implantation
of 50 implantable cardioverter defibrillators (ICDs). Thus 9% of their
population were found to have a primary preve...
The activity monitoring analysis of the UK-HEART study published by
Gall et al. [1] is very welcome. They calculate that screening of 551
ambulant patients with stable heart failure according to NICE guidance [2]
would result in 142 electrophysiology studies (EPS) and the implantation
of 50 implantable cardioverter defibrillators (ICDs). Thus 9% of their
population were found to have a primary prevention indication for ICD
implantation. They conclude that “Overall, these data provide evidence
that implementation of the NICE guidelines for the use of ICDs in primary
prevention is unlikely to lead to an unmanageable increase in EPS or ICD
implantation in UK electrophysiology centres.” We are concerned that this
analysis under estimates the true number of patients who fulfil NICE
primary prevention criteria, and that this conclusion is therefore
unrealistic.
European estimates put the prevalence of heart failure due to LV
dysfunction at 9,000 [3] to 10,000 [4] per million. Screening this
population as envisaged by Gall et al. would require 18,000 to
20,000/million Holter recordings, 2,300 to 2,600/million EPSs and would
identify 800 to 900/million patients requiring ICD implantation. The UK
Heart Study recruited patients between 18 and 80 years with NYHA class I-
III heart failure. 21% of the new incident heart failure patients in UK
are over 80 [5], and 16% have class IV heart failure [5], and would have
been excluded from UK Heart. Excluding these patients from the European
prevalence gives an estimate of 535/million requiring ICD implantation.
Clearly, these figures do not exclude patients with other
contraindications to ICD therapy such as terminal illness, but,
conservatively, this would suggest that over 500/million of the general
population (approximately 30,000 patients in the UK) have a primary
prevention indication for ICD implantation.
Other estimates put the prevalence a little lower; published data
suggest that approximately 3% of the UK population have a history of MI
[3]. Of these, 16% have an EF <_35 _6="_6" _16="_16" of="of" those="those" have="have" non-sustained="non-sustained" vt="vt" on="on" holter="holter" monitoring="monitoring" and="and" _35="_35" sustained="sustained" monomorphic="monomorphic" inducible="inducible" at="at" eps="eps" _7.="_7." this="this" implies="implies" a="a" prevalence="prevalence" primary="primary" prevention="prevention" icd="icd" indications="indications" in="in" the="the" population="population" around="around" _270="_270" million.="million." new="new" incidence="incidence" these="these" can="can" be="be" estimated="estimated" from="from" number="number" mi="mi" survivors="survivors" each="each" year="year" _="_" approximately="approximately" _200000="_200000" uk="uk" giving="giving" figure="figure" for="for" icds="icds" _30="_30" million="million" per="per" year.="year." p="p"/> Both our and Gall et al.’s calculations are hypothetical and have
been based on a variety of estimates and assumptions derived from the
literature. However the number of patients fulfilling NICE criteria is
calculated, it exceeds that suggested by NICE (a total of 50 per million,
which is equivalent to 33 new implants per million per year)[2] by a
factor of more than 10, when both prevalence and new incidence are taken
into account.
All these estimates far exceed the total number of new ICD implants
performed in England (12/million)[8], Europe (31/million)[9] Denmark
(47/million)[10] and even the USA (154/million)[9]. Indications for ICD
implantation in Europe do not in practice include primary prevention, (for
example, 96% of implants in Denmark [10] are for secondary prevention
indications) so these patients, whatever their real number, are currently
not being considered for ICDs at all.
We have recently completed a local audit of cardiac patients
presenting to Freeman Hospital [11], and have found that complying with
NICE guidance for both primary and secondary prevention would require an
extra 2-3 EPS and 2-3 ICDs per week, compared with Gall et al.’s estimate
of one extra ICD per implanting centre per month.
We therefore have concerns about the manageability of the expected
increase in ICD implantation if NICE guidance is to be implemented. We
agree with Gall et al. [1] that implementation of the NICE guidance on the
use of ICDs is a desirable goal but we do not think that this can be
achieved with current resources, at least in the North East. It is
important that we do not underestimate the additional resources required
if we are to plan for the successful implementation of the NICE guidance.
C. J. Plummer, J. M. McComb, Freeman Hospital, Newcastle upon Tyne.
NE7 7DN. UK.
References
(1) Gall NP, Kearney MT, Zaman A, O'Nunain S, Fox KAA, Flapan A, Nolan
J. Implementation of the NICE guidelines for the primary prevention of
mortality from ventricular tachyarrhythmias: implications for UK
electrophysiology centres; activity modelling from the UK-HEART study.
Heart 2001;86:219-220
(4) Cleland JGF, Clark A, Caplin JL. Taking heart failure seriously.
Diagnosis and initiation of treatment are the aspects to concentrate on.
BMJ 2000;321:1095-1096
(5) Johansson S, Wallander M-A, Ruigómez A, Alberto L, Rodríguez G.
Incidence of newly diagnosed heart failure in UK general practice. Eur J
Heart Failure 2001;3:225-231
(6) Hohnloser SH, Klingenheben T, Zabel M, Schöpperal M, Mauß O.
Prevalence, characteristics and prognostic value during long-term follow-
up of nonsustained ventricular tachycardia after myocardial infarction in
the thrombolytic era. J Am Coll Cardiol 1999;33:1895-902
(7) Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley
G. A randomized study of the prevention of sudden death in patients with
coronary artery disease. The Multicenter Unsustained Tachycardia Trial
(MUSTT). N Engl J Med 1999;341:1882-90
(8) Cunningham D. Rickards A. Cunningham M. National Pacemaker and ICD
database, United Kingdom and Republic of Ireland, Annual Report 1998 and
1999. Available from URL http://ccad3.biomed.gla.uk/bpeg
(9) Camm AJ, Nisam S. The utilization of the implantable defibrillator
– a European enigma. Eur Heart J 2000;21:1998-2004
(10) Møller M, Arnsbo P. Danish Pacemaker and ICD Register. 2000.
Available from URL http://www.pacemaker.dk
(11) Plummer CJ, McComb JM. Audit of potential implantable
cardioverter defibrillator (ICD) patients. Europace 2001 Ed. Bloch Thomsen
PE. Monduzzi Editore International Proceedings Division, Bologna, Italy.
2001.
We read with great interest the article by Rallidis et
al. [1] that elevated concentrations of macrophage colony
stimulating factor (MCSF) predict a worse short term
prognosis in patients with unstable angina. Recent studies
have clarified the significance of monocyte-related
cytokines such as MCSF in the development of
atherosclerosis, atheromatous plaque rupture and restenosis
after coronary angioplas...
We read with great interest the article by Rallidis et
al. [1] that elevated concentrations of macrophage colony
stimulating factor (MCSF) predict a worse short term
prognosis in patients with unstable angina. Recent studies
have clarified the significance of monocyte-related
cytokines such as MCSF in the development of
atherosclerosis, atheromatous plaque rupture and restenosis
after coronary angioplasty.
We previously investigated changes in MCSF in the
coronary circulation induced by percutaneous transluminal
coronary angioplasty (PTCA) and their clinical significance
[2]. A 5F Amplatz catheter was placed in the coronary
sinus of 40 patients with angina pectoris, and blood
samples were obtained through the catheter before,
immediately after, and 4 and 24 hours after angioplasty.
MCSF levels in the coronary sinus blood showed a
significant increase 4 and 24 hours after PTCA (from
[mean�}SD] 671�}51 to 942�}63 and to 1,220�}79 pg/mL,
respectively). We performed follow-up coronary angiography
after 6 months; MCSF levels in the coronary sinus blood 24
hours after PTCA in patients with restenosis were
significantly higher than those in patients without
restenosis (1,470�}133 vs. 1,061�}110 pg/mL, P<_0.05. a="a" significant="significant" positive="positive" correlation="correlation" was="was" observed="observed" between="between" mcsf="mcsf" levels="levels" and="and" loss="loss" index="index" r="0.59," p0.01.="p0.01." p="p"/> We also investigated the clinical significance of MCSF
expression in 20 patients with unstable angina [3]. Plasma
levels of MCSF on admission in patients with unstable
angina (736�}74 pg/mL) were significantly higher than those
in patients with stable angina (544�}35 pg/mL) or control
subjects (405�}44 pg/mL). Patients with unstable angina
were further divided into sub-groups according to their
clinical classification [4]; Levels of MCSF in patients who
had anginal attacks at rest within the 48 hours prior to
admission (Braunwald class IIIB) were significantly higher
than those in patients who did not have attacks at rest
(class IB, IIB). Five of the 20 unstable patients who were
refractory to medical therapy and were referred for
emergency coronary revascularization showed marked
elevation of plasma MCSF levels than the other 15 patients
(1,072�}135 vs. 624�}67 pg/mL, p<_0.01. p="p"/> These observations suggest that activation of monocytes/
macrophages by MCSF is involved in vulnerability of
atheromatous plaque as well as neointima formation after
angioplasty, and they support the conclusions of Rallidis
et al.
References
(1) Rallidis LS, Thomaidis KP, Zolindaki MG, Velissaridou
AH, Papasteriadis EG. Elevated concentrations of macrophage
colony stimulating factor predict worse in-hospital
prognosis in unstable angina. Heart 2001;86:92.
(2) Hojo Y, Ikeda U, Katsuki T, Mizuno O, Fukazawa H,
Fujikawa H, Shimada K. Chemokine expression in coronary
circulation after coronary angioplasty as a prognostic
factor for restenosis. Atherosclerosis 2001;156:165-170.
(3) Hojo Y, Ikeda U, Takahashi M, Shimada K. Increased
levels of monocyte-related cytokines in patients with
unstable angina. Atherosclerosis (in press).
(4) Braunwald E. Unstable angina: A classification.
Circulation 1989;80:410-414.
We read with great interest the recent article by Dorsch and Lawrance.[1] Using data from the EMMACE (Evaluation of Methods and Management of Acute Coronary Events) study they derived a simple model for prediction of 30-day mortality in patients with acute myocardial infarction. Their model included age, heart rate, and systolic blood pressure and had very good predictive accuracy with areas under the receiver o...
We read with great interest the recent article by Dorsch and Lawrance.[1] Using data from the EMMACE (Evaluation of Methods and Management of Acute Coronary Events) study they derived a simple model for prediction of 30-day mortality in patients with acute myocardial infarction. Their model included age, heart rate, and systolic blood pressure and had very good predictive accuracy with areas under the receiver operating characteristic curves of 0.79 and 0.76 for the reference and test cohort, respectively.
Risk stratification in acute myocardial infarction and acute coronary syndromes in general is an area of active investigation. Several models [2-5] have been developed for mortality prediction: all of them include age and most include systolic blood pressure and heart rate, the 3 components of the EMMACE model. A significant limitation of those models is that they were derived from trial populations, which are selected and typically have lower mortality compared to non-trial populations. The EMMACE model addresses this concern since all patients with myocardial infarction from 20 adjacent hospitals in the former Yorkshire region were included.
Community populations in different areas of the world may differ and these differences may not be accounted for entirely by the proposed models. That is why we attempted to examine the performance of the EMMACE model in a US patient population of 875 consecutive Olmsted County, MN patients with acute myocardial infarction admitted to the coronary care unit of our institution between 1988 and 1998.[6] Myocardial infarction was defined by the WHO criteria as in the EMMACE study. Compared to the EMMACE population, our patient population was more likely to have hypertension (29.1% vs 44.7%, p<_0.001 and="and" diabetes="diabetes" mellitus="mellitus" _13.0="_13.0" vs="vs" _15.8="_15.8" p0.05="p0.05" less="less" likely="likely" to="to" be="be" currently="currently" smoking="smoking" _33.6="_33.6" _28.3="_28.3" p0.01.="p0.01." women="women" were="were" equally="equally" represented="represented" in="in" both="both" populations="populations" _39.4="_39.4" _38.6="_38.6" p="non-significant).<p"/>
The predicted and the observed 30-day mortality were compared by use of the chi-square test for each decile of the predicted mortality. Thirty-day mortality was 10.3% in our patients compared with 24.4% in the EMMACE population (p<_0.001. the="the" observed="observed" mortality="mortality" was="was" similar="similar" to="to" predicted="predicted" in="in" patients="patients" lower="lower" _5="_5" deciles="deciles" but="but" significantly="significantly" last="last" figure.="figure." predictive="predictive" accuracy="accuracy" of="of" emmace="emmace" model="model" good="good" c-statistic="0.76).<p"/>
Therefore, the EMMACE model overestimated mortality in higher risk patients of our population. Whether this difference resulted from different baseline characteristics or therapy administered is unknown. However, it highlights the difficulty in comparing quality of care between hospitals in different areas of the world; caution should be undertaken when applying a model for mortality prediction in a new patient population. A potential approach would be to repeat the excellent study by Dorsch and Lawrance when different populations are being evaluated to derive a population-specific model.
Emmanouil S. Brilakis
Stephen L. Kopecky
R. Scott Wright
Guy S. Reeder
Brent A. Williams
Ian P. Clements
References
(1) Dorsch MF, Lawrance RA, Sapsford RJ, et al. A simple benchmark for evaluating quality of care of patients following acute myocardial infarction. Heart 2001; 86:150-4.
(2) Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. Jama 2000; 284:835-42.
(3) Boersma E, Pieper KS, Steyerberg EW, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation 2000; 101:2557-67.
(4) Morrow DA, Antman EM, Charlesworth A, et al. TIMI risk score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudy. Circulation 2000; 102:2031-7.
(5) Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators. Circulation 1995; 91:1659-68.
(6) Brilakis ES, Wright RS, Kopecky SL, Reeder GS, Williams BA, Miller WL. Bundle branch block as a predictor of long-term survival after acute myocardial infarction. Am J Cardiol 2001; 88:205-9.
We thank Drs Plummer and McComb for their interest in our estimate of the implications of the recently published NICE guidelines for United Kingdom electrophysiology centres [1]. We agree that an assessment of the workload implications of these guidelines is important for resource planning.
Using data gathered in clinical trials designed for different ends will always require assumptions and can therefor...
We thank Drs Plummer and McComb for their interest in our estimate of the implications of the recently published NICE guidelines for United Kingdom electrophysiology centres [1]. We agree that an assessment of the workload implications of these guidelines is important for resource planning.
Using data gathered in clinical trials designed for different ends will always require assumptions and can therefore be open to criticism. Studies detailing the prevalence of heart failure in the UK population vary in their findings also [2]. Our data, however, are based on a study where stable patients were enrolled by cardiologists in their clinics. Clearly, only a proportion of the
total heart failure population will be seen in this setting. It is unsurprising, therefore, that our estimate is lower than that predicted for the entire UK population.
The actual increase in ICD implantation rates will only become clear through the BPEG database and will depend upon local decision-making processes as to the implementation of a screening process. If all parts of primary, secondary and tertiary care were to be involved, the implications would clearly be considerable. Whether this will be possible in the days of limited resources is uncertain.
NP Gall, MT Kearney, A Zaman, S O'Nunain, KAA Fox, A Flapan, J Nolan.
References
(1) Gall NP, Kearney MT, Zaman A, O'Nunain S, Fox KAA, Flapan A, Nolan J. Implementation of the NICE guidelines for the primary prevention of mortality from ventricular tachyarrhythmias. Implications for UK electrophysiology centres; activity modelling from the UK-HEART study. HEART 2001;86:219-220.
(2) Davies MK , Hobbs FDR , Davis RC , Kenkre JE, Roalfe AK, Hare R, Wosornu D, Lancashire RJ. Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study. LANCET 2001;358:439-44
We read with interest the report of McMahon and colleagues (Heart 2001;86:e1) regarding a case of rapid regression of primary pulmonary hypertension in a 14 month old child. Although the authors describe this as spontaneous regression, the patient underwent two months of continuous nitric oxide therapy prior to resolution of her disease. This case may in fact be similar to our previously reported series of four i...
We read with interest the report of McMahon and colleagues (Heart 2001;86:e1) regarding a case of rapid regression of primary pulmonary hypertension in a 14 month old child. Although the authors describe this as spontaneous regression, the patient underwent two months of continuous nitric oxide therapy prior to resolution of her disease. This case may in fact be similar to our previously reported series of four infants with severe primary pulmonary hypertension who were treated with prolonged
inhaled nitric oxide and heparin therapy (1). Three out of four patients had long term reduction in pulmonary artery pressures that have been sustained in up to 62 months of follow up. The demonstrated ability of inhaled nitric oxide to decrease vascular smooth muscle proliferation, reduce hypoxic lung vessel remodeling and inhibit platelet aggregation may be useful in long-term therapy of primary pulmonary hypertension in children and warrants further prospective study.
(1) Atz, A M, and Wessel, D L. Inhaled nitric oxide and heparin for infantile primary pulmonary hypertension Lancet 1998; 351:1701
Takeda et al. have observed that degree of mitral lateral annular
excursion in mild to moderate aortic stenosis is very close to that in
control group. In this study, both lateral and septal side of mitral
annulus have shown a consistent decrease in long axis excursion with
disease progression. Aortic stenosis may lead to physiological hypertrophy
in early stages of the disease as discussed in hy...
Takeda et al. have observed that degree of mitral lateral annular
excursion in mild to moderate aortic stenosis is very close to that in
control group. In this study, both lateral and septal side of mitral
annulus have shown a consistent decrease in long axis excursion with
disease progression. Aortic stenosis may lead to physiological hypertrophy
in early stages of the disease as discussed in hypertrophy session at the
4th annual meeting of the working group on echocardiography of the ESC.[1]
In a similar way, we have observed that mitral annular circumferential and
longitudinal axis functions are in normal limits as compared to much
lower function in cardiomyopathic patients using real-time 3-dimensional
echocardiography and complex reconstruction methodology in patients with
secondary LV hypertrophy caused by aortic stenosis.[2] In those patients,
left ventricular systolic function had been preserved.
Takeda et al. have shown that long axis excursion is independently related
to both LV mass index and the grade of aortic stenosis. They have
explained that both pathophysiological changes as a result of LV
hypertrophy and increased afterload as a result of aortic stenosis may
together contribute to changes in systolic function in aortic stenosis.
These observations can support that aortic stenosis possibly results in
physiological hypertrophy before existing LV dysfunction.
On the other hand, it is well known that hypertension and cardiomyopathy
are associated with pathological hypertrophy.[3] I believe, this
comprehensive study by Takeda et al. is an important step to predict the
stages of the disease process and aortic stenosis may be the unique
example of physiological hypertrophy conversion to pathological one with
development of LV dysfunction.
Note: I noticed that there may be a discordance between a sentence
and the referred number. In the discussion part, the second sentence is
about wall stress relief in patients with aortic stenosis after the valve
replacement, while marked reference (19th) is related to left ventricular
dysfunction after MI.
References
(1) 4th Annual and plenary meeting of the working group on echocardiography
of the European Society of Cardiology, 2000.
(2) Yalçin F, Tsujino H, Greenberg N, Bauer F, Farias CA, Shiota T,
Lever H, Thomas JD. Real-time three-dimensional echocardiographic
evaluation of mitral annular characteristics in myocardial hypertrophy.
Europ Heart J 1999:291;P1599.
(3) Vinereanu D, Florescu N, Sculthorpe N,. Tweddel AC, Stephens MR, Fraser AG. Differentiation between pathologic and physiologic left
ventricular hypertrophy by tissue doppler assessment of lon-axis function
in patients with hypertrophic cardiomyopathy or systemic hypertension and
in athletes. Am J Cardiol 2001; 88:53-8.
Cardiogenic shock is an ominous complication of myocardial infarction
(MI), occurring in 4 to 7%of cases. The majority of patients have
an ST elevation (Q wave) MI, but cardiogenic shock can occur, although
less frequently after a non-ST elevation (non-Q wave) MI.[1,4]
The
clinical definition of cardiogenic shock is decreased cardiac output and
evidence of tissue hypoxia in the presence of adequ...
Cardiogenic shock is an ominous complication of myocardial infarction
(MI), occurring in 4 to 7%of cases. The majority of patients have
an ST elevation (Q wave) MI, but cardiogenic shock can occur, although
less frequently after a non-ST elevation (non-Q wave) MI.[1,4]
The
clinical definition of cardiogenic shock is decreased cardiac output and
evidence of tissue hypoxia in the presence of adequate intravascular
volume. Hemodynamic criteria for cardiogenic shock are hypotension
(systolic blood pressure <90 mm Hg) and a reduced cardiac index
(CI<2.2 L/min/m2) in the presence of elevated pulmonary capillary
wedge pressure (PCWP > 15 mm Hg). Cardiogenic shock, like other types
of shock, is characterized by systemic hypoperfusion, with consequent
tissue hypoxia and vital organ dysfunction. It must be emphasized that
hypotension is not synonymous with shock. Patients with low blood pressure
may have normal tissue perfusion if systemic vascular resistance (SVR) is
also decreased.
On the other hand, tissue perfusion may be impaired
despite normal blood pressure in the presence of severe sympathetically –
mediated peripheral vasoconstriction. Most patients with acute MI and
cardiogenic shock have severe and extensive coronary artery disease, often
involving all the three major coronary arteries. Fixed coronary stenoses
limit coronary blood flow despite maximal coronary arteriolar dilatation.
Coronary perfusion pressure then becomes the major determinant of coronary
blood flow.
Accordingly, any mild drop in blood pressure can significantly
reduce coronary perfusion pressure and hence coronary blood flow. The
combination of severe diffuse coronary artery disease and prolonged
hypotension are particularly detrimental to patients with cardiogenic
shock. The apparently limited efficacy of thrombolysis in patients with
acute MI complicated by cardiogenic shock may be due to failure to improve
coronary perfusion pressure during administration of thrombolytic agents.
The rate of coronary thrombolysis can be restored to normal levels if the
blood pressure is raised by aggressive use of vasopressors or insertion of
intra-aortic balloon pump.[28,29]
Historically, mortality rate of
cardiogenic shock complicating acute MI is 80 to 90 percent.[5] However,
lower values for in-hospital mortality have been noted in more recent
studies ranging from 56 to 74%.[1,4] This significant reduction
in mortality of cardiogenic shock may be attributed to the increased use
of intra-aortic balloon pump (IABP) and coronary reperfusion strategies
which, by restoring patency of the infarct-related artery, can limit the
infarct size.[2,3] There are promising data on the use of percutaneous
coronary intervention (PCI) for cardiogenic shock complicating acute MI.
The long-term outcome of patients with cardiogenic shock appears to be
improved with early revascularization using either PCI or CABG as
illustrated by the 1-year survival rate from the SHOCK trial.[2] Until
coronary revascularization can be performed, the circulation must be
supported either pharmacologically -by inotropics and vasopressors- or
mechanically by intra-aortic balloon pump. Sympathomimetic inotropic and
vasopressor agents remain the first-line therapy to reverse hypotension
and maintain vital organ perfusion. A second goal of therapy is to
maintain coronary perfusion pressure as high as possible during the
administration of thrombolytic agents to facilitate coronary reperfusion.
Dopamine is often used in cardiogenic shock as it increases myocardial
contractility and supports the blood pressure. Norepinephrine is a potent
vasopressor and is often used when dopamine is inadequate.
In spite of its
potent inotropic effect, dobutamine is less often used in cardiogenic
shock because it produces mild vasodilatation that may increase
hypotension. On the other hand, dopamine and Norepinephrine have several
deleterious effects in the setting of acute MI complicated by cardiogenic
shock. Excessive vasoconstriction in response to vasopressors increase
afterload and may further depress LV function and decrease cardiac output.
Systemic hypoperfusion may occur as a result of decreased cardiac output
and high SVR in spite of the relatively preserved blood pressure.
Furthermore, cardiac work and myocardial oxygen demand are increased
because of vasopressor – induced increase in afterload and heart rate that
may worsen myocardial ischemia. Hence, the potential beneficial effect of
vasopressors on coronary perfusion pressure and myocardial oxygen supply
may be offset by increased demand.
Finally, dopamine may increase whole-
body oxygen uptake - because of its calorigenic effect -and exacerbate
tissue hypoxia. Dobutamine may be particularly useful in cardiogenic shock
if improved tissue oxygenation rather than hemodynamic stability will be
the goal of therapy. In contrast to dopamine and norepinephrine,
dobutamine increases cardiac output, lowers afterload and SVR and improves
tissue perfusion with only minimal increase in myocardial oxygen demand
and whole-body oxygen uptake. We can hypothesize that maintaining adequate
perfusion and oxygenation to the heart, brain and other vital organs may
be more important than simply increasing the blood pressure - by excessive
vasoconstriction - even at the expense of cardiac output, myocardial
oxygen demand and tissue oxygenation. Tissue oxygenation can be monitored
directly by measuring whole-body oxygen uptake (by calorimetery) or
indirectly by calculating oxygen extraction ratio (O2 ER = SaO2 –SvO2/
SaO2) where SaO2 is arterial O2 saturation and SvO2 is mixed venous O2
saturation – of blood taken from pulmonary artery with Swan-Ganz catheter.
Other parameters of tissue oxygenation include arterial blood lactate and
gastric mucosal pH. Similarly, cerebral perfusion and oxygenation can be
evaluated by calculating cerebral O2 extraction ratio (cerebral O2 ER =
SaO2 – SvjO2/ SaO2) where SvjO2 is O2 saturation of blood taken from
internal jugular vein. Maintaining adequate coronary perfusion - while
preventing significant increase in myocardial O2 demand - is of critical
importance during pharmacologic and mechanical therapy of cardiogenic
shock. Myocardial oxygenation (reflecting the balance between O2 supply
and demand) can be evaluated directly by measuring myocardial blood
lactate, oxygen extraction ratio, regional pH, PCO2 and base deficit
during transvenous catheterization of the coronary sinus (that drains most
of the cardiac veins and opens into the right atrium). Adequacy of
coronary blood flow can be assessed indirectly by repeated
echocardiography to demonstrate any significant changes in ejection
fraction and regional wall-motion abnormalities. Serial ECGs can also be
used to detect early ST segment -T wave changes suggestive of increased
size of infarct or ischemic area. Mechanical ventilation may be
particularly important in cardiogenic shock - regardless of the blood
gases – as it significantly reduces oxygen uptake (VO2) - by allowing
adequate sedation, analgesia and muscle paralysis – in a clinical setting
of decreased oxygen delivery to the tissues (DO2). Furthermore, mechanical
ventilation can improve arterial oxygenation and increase myocardial O2
supply.
In conclusion, it may be more appropriate to titrate the
pharmacologic therapy of cardiogenic shock according to the parameters of
myocardial and tissue oxygenation rather than to the hemodynamic
parameters alone, while waiting for coronary revascularization.
References
1. Hochman, js, Boland, j, Sleeper, et al .and the SHOCK Registry
Investigators. Current spectrum of cardiogenic shock and effect of early
revascularization on mortality: Results of an international registry.
Circulation 1995; 91: 873.
2. Holmes, DR Jr, Bates, ER, Kleinman, NS, et al. Contemporary
reperfusion therapy for cardiogenic shock: The GUSTO-1 trial experience.
Global Utilization of Streptokinase and Tissue Plasminogen Activator for
Occluded Coronary Arteries.J Am Coll Cardiol 1995; 26:668.
3. Goldberg, RJ, Samad, NA, Yarzebski, J, et al. Temporal trends in
cardiogenic shock complicating acute myocardial infarction. N Engl j
Med1999; 340:1162.
4. Holmes, DR Jr, Berger, PB, Hochman, Js, et al. cardiogenic shock
in patients with acute ischemic syndromes with and without ST- segment
elevation. Circulation 1999; 100:2067.
5. Goldberg, RJ, Gore, JM, Alpert, JS, et al. Cardiogenic shock after
acute myocardial infarction.Incidence and mortality from a community wide
perspective, 1975 -1988. N Engl J Med 1991; 325: 1117.
Dear Editor,
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Dear Editor
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Dear Editor
Cardiogenic shock is an ominous complication of myocardial infarction (MI), occurring in 4 to 7%of cases. The majority of patients have an ST elevation (Q wave) MI, but cardiogenic shock can occur, although less frequently after a non-ST elevation (non-Q wave) MI.[1,4]
The clinical definition of cardiogenic shock is decreased cardiac output and evidence of tissue hypoxia in the presence of adequ...
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