It would seem that the K+(atp) channel opener pinacidil and closer
glibenclamide might exert their effects by deceasing and increasing
respecitively the rates of ATP resynthesis [1,2]. The implication is that
the primary determinants of ATP resynthesis, pH, substrate availability
for oxidative phosphorylation and body temperature, are important
determinants of the degree of H+(atp) channel openess a...
It would seem that the K+(atp) channel opener pinacidil and closer
glibenclamide might exert their effects by deceasing and increasing
respecitively the rates of ATP resynthesis [1,2]. The implication is that
the primary determinants of ATP resynthesis, pH, substrate availability
for oxidative phosphorylation and body temperature, are important
determinants of the degree of H+(atp) channel openess and hence the
effects of pinacidil and glibenclamide. Conceivably the drugs might even
have opposing actions in different myocytes in the same myocardium.
Consider the possibilities in terms of the myocyte buddy hypothesis.
"Dyslipidaema" is the plasma reflection of the heterogeneity of
cellular metabolic needs and their collective mass action effect upon
humoral, hepatic, adrenal and adipocyte modulators of fatty acid
metabolism. In stressed myocardium substrate utilisation by each myocyte
will be primarily determined but its own pH, [AMP], and exposure to
humoral agents such as the "exercise factor" IL-6 and other cytokines[3].
A shift from dependence upon glucose for ATP resynthesis to fatty
acids might be induced in stressed myocytes by inhibition of
phosphofructokinase induced by the fall in pH and/or rise in [AMP] and/or
by inhibiton of the pyruvate dehydrogenase complex by the release of
cytokines. In terms of the myocyte buddy hypothesis that should mean that
some myocytes are more dependent upon fatty acids than others, the greater
the cellular demand the greater the mass action effect in determining the
accompanying plasma lipid profile. The inference is that the avalaility of
ATP, the degree of openess of K+(atp) channels and the potential for
pinacidil and glibenclamide to either open or close them might vary from
myocyte to myocyte especially in stressed myocardium.
Propranalol decrases myocardial uptake of fatty acid nd increases the
uptake of glucose, the reverse of the ompensatory lipid shidt that occurs
with exercise, and causes more myocardial depression in hearts perfused
with fatty acids than in those perfused with glucose [4]. The inference is
that propranalol decreases the efficiency of ATP resynthesis per unit
volume of flowing blood and hence the avalaility of ATP to meet the needs
of stressed myocytes at that moment [5].
The cardioprotective effects of propranalol might well be the product
of an increase in the degree of openess of the K+(atp) channels. In which
case support for the most stressed myocytes by trmsof the myocyte buddy
hypothesis should also be compromised by the propranalol and the
likelihood of developing apoptosis or even necrosis increaed in the most
stressed myocytes, those dependent upon fatty acids for their ATP
resyntheis by residual oxidative phosphorylation. In other words
proprnalol might be cytoprotective in most of the myocardium but could
precipitate the development of confluent areas of myocyte apoptosis and
even necrosis in the most stresed regions of compromised myocardium.
That is precisely what happened wit beta blockers in the ISIS-1 trial.
In this large randomised trial of early beta-blockade in acute
myocardial infarction (ISIS-1), almost all the reduction in mortality
associated with the use of atenolol occurred on the day of admission or on
the subsequent day [6]. "Of 217 early deaths adequate records were
available for 193 (79 allocated atenolol and 114 allocated control). In
the atenolol group, necropsy had shown cardiac rupture in 5 patients, and
a further 15 in whom necropsy had not been done had had electro-mechanical
dissociation (total, 20 early deaths from these causes); among control
patients the corresponding numbers were 17 and 37 (total, 54 such deaths).
Electro-mechanical dissociation was probably a manifestation of acute
rupture, and the observed difference in the numbers with this complication
was responsible for much of the difference in early mortality. There was a
slightly higher incidence of fatal ventricular fibrillation and aortic
dissection in the control group, and of bradycardia/asystole in the
atenolol group"[7].
If beta blockers can cause myocardial rupture by precipitating
confluent areas of myocyte apoptosis and necrosis might they might also
cause myocardial fibrosis, ventricular aneurysms and chronic heart failure
as previously proposed [8]. If thy do pinacidil or glibenclamide could
have similar effects.
references
(1). Lembert N, Idahl LA, Ammon HP. K-ATP channel independent effects
of pinacidil on ATP production in isolated cardiomyocyte or pancreatic
beta-cell mitochondria.
Biochem Pharmacol. 2003 Jun 1;65(11):1835-41.
(2). Muller G, Wied S, Wetekam EM, Crecelius A, Unkelbach A, Punter J.
Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in
vitro by the sulphonylureas, glimepiride and , is correlated with
modulations of the cAMP regulatory cascade.
Biochem Pharmacol. 1994 Aug 30;48(5):985-96.
(3). Oxygen supply dependency: has it any clinical relevance?
Richard G Fiddian-Green (8 September 2004) eLetter re: HJ Silverman, J
Abrams, and LJ Rubin
Effects of interleukin-2 on oxygen delivery and consumption in patients
with advanced malignancy
Chest 1988; 94: 816-821
(4). Opie LH, Thomas M. Propranolol and experimental myocardial
infarction: substrate effects. Postgrad Med J. 1976;52 Suppl 4:124-32.
(5). The need for a moratorium on use of beta blockers?
Richard G Fiddian-Green (7 September 2004) eLetter re: P.J. Devereaux,
Salim Yusuf, Homer Yang, Peter T.-L. Choi, and Gordon H. Guyatt
Are the recommendations to use perioperative ß-blocker therapy in patients
undergoing noncardiac surgery based on reliable evidence?
CMAJ 2004; 171: 245-247
(6). Randomised trial of intravenous atenolol among 16 027 cases of
suspected acute myocardial infarction: ISIS-1. First International Study
of Infarct Survival Collaborative Group.
Lancet. 1986 Jul 12;2(8498):57-66.
(7). Mechanisms for the early mortality reduction produced by beta-
blockade started early in acute myocardial infarction: ISIS-1. ISIS-1
(First International Study of Infarct Survival) Collaborative Group.
Lancet. 1988 Apr 23;1(8591):921-3. Erratum in: Lancet 1988 Jul 30;2
(8). The need to manage heart failure from an early age
Richard G Fiddian-Green
bmj.com, 6 Nov 2002 eLettr re: Martin R Cowie and Alex Zaphiriou
Recent developments: Management of chronic heart failure
BMJ 2002; 325: 422-425
As cardiac surgeons we read and reread the editorial by Ashrafian
and
Bogle initially with interest and subsequently bemusement looking for a
definitive message. The title was clear enough; the editorial was not.
The conclusion that good practice will be served if “patients are
adequately counselled on the benefits of good dental hygiene and a
discussion is undertaken and documented on the ri...
As cardiac surgeons we read and reread the editorial by Ashrafian
and
Bogle initially with interest and subsequently bemusement looking for a
definitive message. The title was clear enough; the editorial was not.
The conclusion that good practice will be served if “patients are
adequately counselled on the benefits of good dental hygiene and a
discussion is undertaken and documented on the risks/benefits of
antibiotic prophylaxis” is superficially attractive if one ignores the
practicalities of who is making the decision and on what basis. Is this
the responsibility of cardiologist or dentist? Does this mean the
patient
agreeing to bad advice is acceptable? I agree that dental practitioners
are independent practitioners and carry legal responsibility for their
commission (antibiotic administration) – but omission is equally
legally
liable. Whose advice should they follow and on what basis?
The representative cardiological bodies in UK, USA and Europe have
all published guidelines on the prevention of infective endocarditis.
Their guidance is clear. The guidance from BSAC on the other hand
carries
with it a feeling of selfrighteousness but its position is not
rational.
Ideally the working party felt a prospective double blind trial should
be
carried out and that withholding antibiotic prophylaxis for dental
procedures was radical but logical. That being the case why compromise?
If
there are 1.35 million dental procedures performed on “at risk”
patients
each year (and how reliable is that figure?) there is certainly a
substantial pool available for randomisation – why not push hard for
what
is believed to be right?
The science of endocarditis is clear enough – valves become
infected
secondary to bacteraemia. The argument that rabbit models do not
replicate
strictly the pathogenesis of endocarditis in humans and as such the
evidence is questionable confines much of 20th century progress to the
intellectual dustbin. The incidence of endocarditis will depend on the
organism type, the immune status of the patient and the bacteriological
load. The argument that the patients with cardiac abnormalities are at
risk all year round and therefore should not be covered at recognizable
points when bacteraemia is predictable and can be adequately covered
beggars belief. People die in cars despite or because of seatbelts –
this
does not render ‘belting up’ impractical or inappropriate nor reduce
its
effectiveness in saving lives. The risk of antibiotic related death
from
penicillin anaphylaxis (quoted in the editorial) as five times higher
that
the risk of IE is unreferenced (and in our experience unbelievable) and
gives no indication of IE risk without antibiotics. Patients undergoing
dental procedures develop bacteraemias with a higher bacteriological
load
than the background risk from chewing or brushing. Doctors and dentists
cannot cover patient risk at all times. However they have a duty to
reasonably cover risks that are recognizable and potentially treatable.
No
treatment is 100% effective: antibiotic prophylaxis should not be
expected
to be so. Failure to stop all events does not indicate ineffectiveness
in
the majority. If the philosophy followed is that the risk of dental
treatment is tiny why cover any patients at all – the argument of
covering
patients at particularly high risk if they become infected applies to
all
patients not just those with prostheses or shunts. Endocarditis as a
whole
carries a mortality of at least 20% despite best available management.
Likewise, if the background risk is so small, why should a patient who
has
suffered endocarditis represent a higher risk of infection than one,
with
equivalent pathology, who has not? This does not appear a rational
stance
(from a group who require hard evidence). Isn’t this emotion rather
than
science?
The BSAC guidelines go on to outline indications for non-dental
procedures which by their own admission are “inferred by two equally
unsatisfactory sources” – the chance of a procedure causing bacteraemia
and whether such procedures have been anecdotally linked to
endocarditis –
exactly the evidence they find uncompelling in relation to dental
prophylaxis. It does not appear reasonable to adopt two differing
levels
of proof for the same type of evidence.
Bacterial endocarditis is a severe life threatening infection with
significant mortality and morbidity which despite best efforts and
prophylactic therapy continues to present on a regular basis in a
typical
cardiological and cardiac surgical practice. Most clinicians can
anecdotally confirm the association of infection following dental
intervention. Appendix 1 in the BSAC guidelines states “patients should
concentrate on achieving and keeping a high standard of oral and dental
hygiene, as this does reduce the risk of endocarditis.” The presumption
is
minimisation of the level of bacteraemia associated with chewing and
brushing will reduce the background risk of endocarditis. The same
rational should therefore be applied to recognizable periods of
increased
bacteraemia.
The advice from BSAC has produced a situation where confusion
reigns.
Although dentists may not use the defence of the “the cardiologist made
me
do it” likewise “BSAC told me so” is unlikely to be more effective.
Recommendations of this nature adopted unilaterally against the
best
advice of representative cardiological bodies put dentists in an
invidious
position. They will be liable for omissions in cover and are unlikely
to
be supported if the treatment given runs contrary to the
recommendations
of the patient’s cardiologist. I would doubt clinicians outside the UK
are
likely to find the reasoning of BSAC compelling or defensible.
Patients deserve clear and consistent advice from their
clinicians.
Unfortunately the advice inherent in the guidelines and your editorial
will not have helped to foster either.
Mr John AC Chalmers FRCS
Consultant Cardiac Surgeon
The Cardiothoracic Centre
Thomas Drive
Liverpool
L14 3PE
Mr D M Pullan FRCS
Consultant Cardiac Surgeon and Clinical Director
The Cardiothoracic Centre
References
1. Ashrafian H, Bogle R. Antimicrobial prophylaxis for endocarditis: Emotion or science Heart 2007; 93:5-6
2. Gould FK, Elliott TSJ, Foweraker J et al. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Therapy J Antimicrob Chemother 2006; 57: 1035-42
The editorial by Ashrafian and Bogle[1] suggests that the authors
have little clinical experience in the management of patients with
infective endocarditis (IE). The body of cardiologists and cardiac
surgeons in Europe, North America and the UK would disagree that the BSAC
guidelines are important or “a step in the right direction” and almost
certainly the guidelines will be disregarded by the rest o...
The editorial by Ashrafian and Bogle[1] suggests that the authors
have little clinical experience in the management of patients with
infective endocarditis (IE). The body of cardiologists and cardiac
surgeons in Europe, North America and the UK would disagree that the BSAC
guidelines are important or “a step in the right direction” and almost
certainly the guidelines will be disregarded by the rest of the world as
an eccentricity not based on any evidence whatsoever. Without doubt, they
are out of line with the views of physicians who have cared for patients
with IE over the last 50 years and of those who continue to have this
responsibility. The Joint Formulary Committee of the British National
Formulary and our dental colleagues would do well to take note of the
advice from specialist cardiologists from Europe and the USA regarding
antibiotic prophylaxis (ABP) for those at risk of IE and remember the
devastating consequences that often occur in those patients who are
unfortunately affected. Sadly, within our own Centre we have recently seen
two patients who developed IE after dental treatment who despite
requesting ABP from their dentist, were told that based on the new BSAC
guidelines ABP was not necessary and hence not administered.
Although a very large randomised controlled clinical trial of ABP
prior to dental treatment in those patients considered to be at
high/moderate risk of IE because of their cardiac structural abnormality
might help quantify the benefit/risks of ABP, we think it would prove
difficult to obtain ethical approval and even the patients’ consent for
such a study. With regards to the cost-effectiveness and safety of oral
amoxicillin, we believe it is very cost-effective at ₤1.50 per 3G
sachet, set against the high cost of a prolonged in-patient stay for
parenterally administered antibiotics, the high morbidity and mortality
and the need for surgery in those individuals with the serious destructive
cardiac and extracardiac complications of IE. Although anaphylaxis may
occur as an allergic response to penicillin, this is extremely rare and
not a reason for the omission of ABP.
Patients who place their trust in health professionals to do
everything in their power to protect them deserve a sensible cautious
approach from their physician to diminish the risk of developing a life-
threatening illness with high morbidity and mortality. Dentists look to
cardiologists and not microbiologists for advice about the need for ABP
for patients with cardiac abnormalities that place them at increased risk
of IE. Not to offer ABP to those patients who cardiologists consider to be
at risk of IE is a disservice and in most countries in the Western World
would be considered medico-legally negligent. Dentists will find it
difficult to obtain the support of the patient’s cardiologist when
disaster strikes their patient as a result of omitting ABP when this has
been recommended.
Dr David R Ramsdale MD FRCP, Consultant Cardiologist and Dr Nick D
Palmer MD MRCP, Consultant Cardiologist,
The Cardiothoracic Centre,
Thomas Drive,
Liverpool.
Reference
1. Ashrafian H and Bogle RG. Antimicrobial prophylaxis for endocarditis:emotion or science? Heart 2007;93:5-6.
In the report by Ashrafian1 and Bogle, the authors highlight new
recommendations by the British Society for Antimicrobial Chemotherapy to
limit prophylaxis to high-risk patients with previously documented
endocarditis or surgical shunt/valve procedures (1). Although dental
prophylaxis have an impact on systemic disease, they do not eliminate
bacteremia altogether. Thus, in addition to antibiotic the...
In the report by Ashrafian1 and Bogle, the authors highlight new
recommendations by the British Society for Antimicrobial Chemotherapy to
limit prophylaxis to high-risk patients with previously documented
endocarditis or surgical shunt/valve procedures (1). Although dental
prophylaxis have an impact on systemic disease, they do not eliminate
bacteremia altogether. Thus, in addition to antibiotic therapy, education
and additional treatment modalities should also be available to prevent
systemic conditions following dental procedures (2-3).
Reports indicate that regular postgraduate courses may be an
effective avenue to educate practioners on appropriate antibiotic usage in
patients with endocarditis. (4). As well, treatment options like stannous
fluoride (5) and preventative care (6) may provide additional systemic
protection to patients. Finally, a review of individual dental practices
may also curb inappropriate antibiotic usuage (7).
References
1. Ashrafian H, Bogle RG. Antimicrobial prophylaxis for endocarditis: emotion or science? Heart 2007; 93: 5-6.
2. Ito HO. Infective endocarditis and dental procedures: evidence,
pathogenesis, and prevention. J Med Invest. 2006; 53(3-4):189-98
3. Brincat M, Savarrio L, Saunders W. Endodontics and infective endocarditis--is antimicrobial chemoprophylaxis required? Int Endod J. 2006; 39(9):671-82.
5. Ramji N, Baig A, He T, Lawless MA, Saletta L, Suszcynsky-Meister E, Coggan J. Sustained antibacterial actions of a new stabilized stannous fluoride dentifrice containing sodium hexametaphosphate. Compend Contin Educ Dent. 2005; 26(9 Suppl 1):19-28.
6. Gottehrer NR, Berglund SE. Antimicrobial host response therapy in periodontics: a modern way to manage disease. Dent Today. 2006 Sep;25(9):84-7.
7. Chate RA, White S, Hale LR, Howat AP, Bottomley J, Barnet-Lamb J, Lindsay J, Davies TI, Heath JM. The impact of clinical audit on antibiotic prescribing in general dental practice. Br Dent J. 2006; 201(10):635-41.
The debate on the role of antimicrobial prophylaxis to prevent
infective endocarditis (IE) has intensified as a consequence of the
recently published guidelines from the Working Party of the British
Society for Antimicrobial Chemotherapy (BSAC). In the review by Ashrafian
and Bogle, reference is made to the dental community’s satisfaction with
these new guidelines, highlighting a “victory for scien...
The debate on the role of antimicrobial prophylaxis to prevent
infective endocarditis (IE) has intensified as a consequence of the
recently published guidelines from the Working Party of the British
Society for Antimicrobial Chemotherapy (BSAC). In the review by Ashrafian
and Bogle, reference is made to the dental community’s satisfaction with
these new guidelines, highlighting a “victory for science and common
sense”. Cardiologists are likely to question the validity of such a
statement. The decision by BSAC to exclude patients deemed at
“intermediate risk” of developing endocarditis from bacteraemia, induced
by dental or surgical procedures is raising alarm bells in the cardiology
community. Cardiologists are the people most able to risk stratify
patients with acquired or congenital heart disease in relation to IE
prophylaxis. For example, Ashrafian and Bogle quote mitral valve prolapse
(MVP) in relation to the need for prophylaxis. MVP associated with a
turbulent jet of mitral regurgitation is more likely to produce
endocardial disruption than ‘slight prolapse of the posterior mitral
leaflet’, yet both are regarded equal under the BSAC guidelines.
A change in clinical practice will occur with the BSAC guidelines
which is certain to cause confusion both to the patient and the dentist
(or any other surgical practitioner) involved in patient care. Over the
years, patients, cardiologists and dental practitioners have communicated
well. Dental practitioners will often write to cardiologists seeking
advice on specific antibiotic dosage or timing etc. and this may have
positively contributed to the present low annual case load of IE. No
cardiologist would argue against the statement that many cases of IE are
of non-dental origin but many are likely to question the decision to
withhold prophylaxis for general surgical or genito-urinary procedures in
patients with haemodynamically significant murmurs.
Ashrafian and Bogle highlight the risk of anaphylaxis associated with
severe penicillin allergy. Most allergies to antibiotics are not life-
threatening however and will often have declared themselves previously by
taking a careful medical history. Several alternative antibiotics are
also now available to substitute for a penicillin preparation when
concerns over potential allergy are raised.
Cardiologists are at the ‘front line’ in the treatment of patients
with IE and recognise the high morbidity and mortality associated with the
condition. It is unlikely therefore that the British Cardiovascular
Society will support the new guidelines. It is extremely unlikely
organisations such as the American Heart Association will do so also for
fear of litigation issues. The benefits of antibiotic prophylaxis for IE
outweigh the risk for more patients than is presently recommended by the
BSAC. The debate must continue.
We have read with great interest the article by Roudaut et al entitled
"Thrombosis of prosthetic heart valves: Diagnosis and therapeutic
considerations" published in the last issue of your journal.(1)
According to the authors, the first therapeutic consideration in
obstructive left-sided prosthetic valve thrombosis (PVT) should be surgery
and thrombolysis should be reserved for patients with contrain...
We have read with great interest the article by Roudaut et al entitled
"Thrombosis of prosthetic heart valves: Diagnosis and therapeutic
considerations" published in the last issue of your journal.(1)
According to the authors, the first therapeutic consideration in
obstructive left-sided prosthetic valve thrombosis (PVT) should be surgery
and thrombolysis should be reserved for patients with contraindications to
surgery. The Consensus Conference recommended surgical treatment for
critically unstable patients (NYHA class III-IV) and thrombolysis for
those with high surgical risk or clear contraindications to surgery. In
hemodynamically stable patients (NYHA class I-II) full anticoagulation
with heparin has been the recommended treatment. (2)
However, more recent data have shown that thrombolysis is superior to
surgery in the most critical patients (class III-IV) and to heparin when a
non obstructive thrombosis is present. (3)
This therapeutic decision was based fundamentally on the occurrence of
embolism. Roudaut himself (4) demonstrated that embolic events post-
thrombolysis were less frequent and more benign than previously thought.
Alpert recommended in an editorial that guidelines should be revised and
proposed thrombolysis for patients in NYHA classes III-IV as initial
therapy, reserving surgery for the patients who fail to respond to this
approach. (5)
In NYHA Class IV patients with PVT published results show a lower
mortality with thrombolysis (13%) than surgery (33%). (6)
Reviewing the published literature Lengyel cited post-thrombolysis
mortality of 5% vs 30% post-surgery. In 89 NYHA Class IV patients from
five different studies, late post-thrombolysis mortality was 7% compared
to 17 to 54% post-surgery. In NYHA Class I-III patients mortality was
approximately 5% with both therapeutic approaches. (7)
In 2005 Lengyel, published a letter in the Journal of the American College
of Cardiology with results of thrombolysis in 53 studies in different time
periods (1974-1995 vs 1996-2003). The number of treated episodes was
similar at 235 vs 234, success rate increased from 77% to 90%, embolic
events decreased from 13% to 4% and deaths from 7.5% to 2.5. The author
thus considers thrombolysis the first therapeutic choice in patients with
PVT, independent of the functional class and the thrombus size, if there
are no contraindications for it. (8)
Current data of surgical series have reported elevated rates of mortality.
Durrleman and coworkers presented a series of 39 patients with PVT over a
20 year-period who underwent thrombectomy or valve replacement with an
associated mortality of 25% and 41%, respectively.(9)
Oskokeli et al, in 30 patients with left-side PVT, reported a post-
operative early hospital mortality of 7.1% (NYHA classes II-III) and
31.3% (NYHA IV) (10) and Toker et al, in 63 cases a total mortality of 20,6%. (11)
In our experience of a series of 68 patients with a diagnosis of PVT
treated with thrombolysis, therapeutic success was achieved in 62 patients
(91,2%) and failure in 6 patients (8,8%). In NYHA IV patients the success
rate was 88.9% (32/36 patients). Systemic embolism occurred in five
patients (three cerebral and two peripheral). We used recombinant
streptokinase (250 000 UI / 30 min and continuous infusion 100 000 UI / h,
up to 72 hours). This also appears to be the most widely used and
recommended protocol according to the literature. (12)
Despite advances in surgery; anesthesia and peri-operative care, the
evidence is in favour of thrombolytic treatment for PVT due to its high
effectiveness, easy applicability, low complication rate and cost.
In agreement with other authors, we use and recommend thrombolysis as the
first therapeutic choice for patients with PVT, provided there are no
contraindications, regardless of the degree of valve obstruction, NYHA
functional class or thrombus size. Surgery should be reserved for those
patients with major contraindications or failure of thrombolysis.
REFERENCES
1. Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: Diagnosis and therapeutic considerations. Heart 2007;93:137-42.
2. Lengyel M, Fuster V, Keltai M, Roudaut R, Schulte HD, Seward JB, et al. Guidelines for management of left-side prosthetic valve thrombosis: a role for thrombolytic therapy. Consensus Conference on prosthetic valve thrombosis. J Am Coll Cardiol 1997;30:1521-6.
3. Lengyel M, Horstkotte D, Völler H, Mistiaen WP. Recommendations for the Management of Prosthetic Valve Thrombosis. J Heart Valve Dis 2005;14:567-75.
4. Rodaut R, Lafitte S, Rodaut MF, Courtault C, Perron JM, Jais C, et al. Fibrinolysis of mechanical prosthetic valve thrombosis: a single center study of 127 cases. J Am Coll Cardiol 2003;41:653-8.
5. Alpert J. The thrombosed prosthetic valve. Current recommendations
based on evidence from the literature. J Am Coll Cardiol 2003;41:659-60.
6. Lengyel M, Vandor L. The role of thrombolysis in the management of left-sided prosthetic valve thrombosis: a study of 85 cases diagnosed transesophageal echocardiography. J Heart Valve Dis 2001;10:636-49.
7. Lengyel M. Management of prosthetic valve thrombosis. J Heart Valve Dis 2004;13:329-334.
8. Lengyel M. Thrombolysis should be regarded as first-line therapy for prosthetic valve thrombosis in the absence of contraindications. J Am Coll Cardiol 2005;45:325.
9. Durrleman N. Pellerin M, Bouchard D, Hebert Y, Cartier R, Perraul LP, et al. Prosthetic valve thrombosis: twenty-year experience at the Montreal Heart Institute. J Thorac Cardiovasc Surg 2004;127:1388-92.
10. Ozkokeli M, Sensoz Y, Ates M, Ekinci A, Akcar M, Yekeler I. Surgical treatment of left-sided prosthetic valve thrombosis: short and long-term results. Int Heart J 2005;46:105-11.
11. Toker ME, Eren E, Balkanay M, Kirali K, Yarartas M, Caliskan A, et al. Multivariate analysis for operative mortality in obstructive prosthetic valve dysfunction due to pannus and thrombus formation. Int Heart J 2006;47:237-45.
12. Cáceres-Lóriga FM, Pérez-López H, Morlans-Hernández K, Facundo-Sánchez H, Santos-Gracia J, Valiente-Mustelier J, et al. Thrombolysis as first choice therapy in prosthetic heart valve thrombosis. A study of 68 patients. J Thromb Thrombolysis 2006;21:185-90.
With interest we read the paper by Lofiego et al. on a long-term
follow-up of 65 patients with left ventricular
hypertrabeculation/noncompaction (LVHT).[1] We want to add some points and
raise some concerns:
The prevalence of neuromuscular disorders (NMDs) among patients with LVHT
has been reported to be up to 82%.[2] The low rate of 9% in the presented
study may be attributed to the fact that the pat...
With interest we read the paper by Lofiego et al. on a long-term
follow-up of 65 patients with left ventricular
hypertrabeculation/noncompaction (LVHT).[1] We want to add some points and
raise some concerns:
The prevalence of neuromuscular disorders (NMDs) among patients with LVHT
has been reported to be up to 82%.[2] The low rate of 9% in the presented
study may be attributed to the fact that the patients were not
systematically screened for NMDs. Under these aspects the rate of NMDs in
Lofiego’s study is high and most surprising. Why were the included
patients not systematically referred to a neurologist in light of these
findings and previous recommendations to examine all LVHT patients
neurologically?[3] Which type of muscular dystrophy was diagnosed in the 4
patients mentioned in the results? In the discussion, but not in the
results, a patient with Duchenne-muscular-dystrophy is mentioned. The
authors mention a patient with limb-girdle-muscular-dystrophy with LVHT, a
NMD in which LVHT has not been observed thus far.[3] Which type of limb-
girdle-muscular-dystrophy did the patient suffer from and was there a
correlation between the cardiac abnormalities and the severity of the
muscular abnormalities?
There are conflicting results concerning the need to generally
anticoagulate patients with LVHT [4]. The idea that the rate of
thromboembolism is increased in LVHT is intriguing, but it is only
substantiated by case reports or case studies. In a study on 62 LVHT
patients, no increased rate of stroke/embolism was found in comparison
with control patients, matched for age, sex, and systolic function.[5]
Thus, it is not understandable why all patients with an EF <30% (in the
discussion <35%) were anticoagulated, irrespective if they had atrial
fibrillation or not.
Were sources of thromboembolism other than LVHT
excluded in patients with LVHT and a history of thromboembolism?
The rate of patients receiving oral anticoagulation was 62% in the
symptomatic group but only one had atrial fibrillation at inclusion, and 5
developed it obviously during follow-up. How many of the remaining
patients had a history of thromboembolism or reduced systolic function?
Which was the indication for oral anticoagulation in the 4 non-symptomatic
patients?
Detection of only 65 LVHT patients within 14 years (1991 respectively 1995
to 2004) appears to be lower than previously reported.[6] How to explain
this low prevalence of LVHT in the two centres?
How to explain that among non-symptomatic LVHT familiarity was found in
71% as compared to 17% in the symptomatic LVHT cases? If this is
attributable to the non-systematic search for familial cases, such figures
are misleading and should be considered with caution.
How to explain the discrepancy between the follow-up duration of 6 to 193
months and an observational period of 14y (168m)?
Concerning the follow-up character of the study it would be interesting to
know how many of the non-symptomatic patients became symptomatic and how
many developed heart failure during the observational period?
Overall, the presented data indicate that all patients with LVHT require a
neurological investigation, that it is actually not evidence-based to
anticoagulate LVHT patients unless classical indications are present and
that systematic family screening is warranted to assess a possible genetic
background of the abnormality.
We read with interest the article by Sutton et al. entitled
‘Predictors of outcome after percutaneous treatment for cardiogenic
shock.’ [1]. We would like to congratulate the authors on attempting to
identify risk factors that predict outcome in patients with cardiogenic
shock who undergo percutaneous coronary intervention (PCI). We would,
however, like to make a few points regarding the study that...
We read with interest the article by Sutton et al. entitled
‘Predictors of outcome after percutaneous treatment for cardiogenic
shock.’ [1]. We would like to congratulate the authors on attempting to
identify risk factors that predict outcome in patients with cardiogenic
shock who undergo percutaneous coronary intervention (PCI). We would,
however, like to make a few points regarding the study that may have
influenced its findings.
The study was conducted between 1995 to 2002 with a total of 113
patients recruited. The use of coronary stents in the study was only 48%
and use of abciximab only 25%. Advances in stent technology and increasing
evidence from trials on the use of abciximab during PCI suggest that both
these treatment options improve outcomes in patients undergoing PCI [2,3].
The use of stents in the study by Sutton et al. is low and probably
reflects the fact that stents were not being used routinely for PCI in the
mid to late 90’s. Modern management has changed considerably, with stent
use in acute myocardial infarction being better than just balloon
angioplasty [4]. Along with this trend of increasing stent usage, the use
of glycoprotein IIb/IIIa receptor antagonists has also increased with
several large trials showing clear benefit of the use of such agents [3].
Evidence also exists for the use of clopidogrel in all patients undergoing
PCI, unless contraindicated; emerging data also suggests that the initial
loading dose should be 600mg [5]. Sutton et al. only used clopidogrel if one
or more stents were used and even then ticlopidine may have been used
instead. Less than 50% would therefore have received clopidogrel in this
trial and those that did would have received a lower than recommended
dose.
The low use of stents, glycoprotein IIb/IIIa receptor antagonists,
and clopidogrel are all likely to have influenced the outcome of the trial
and hence the conclusions drawn by the investigators. While we welcome the
study and, once again, congratulate the authors on their attempts at
identifying those at highest risk of death we would like to point out the
limitations of the study in relation to advances in stent and drug use.
References
1. Sutton AGC, Finn P, Hall JA, et al. Predictors of outcome after
percutaneous treatment for cardiogenic shock. Heart 2005; 91: 339-344.
2. ACC/AHA guidelines for the management of patients with ST-
elevation myocardial infarction-executive summary. Circulation 2003; 110:
588-636.
3. Randomized, placebo-controlled trial of platelet glycoprotein
IIb/IIIa blockade with primary angioplasty for acute myocardial
infarction. Circulation 1998; 98: 734-741.
4. Schomig A, Ndrepepa G, Mehilli J, et al. A randomized trial of
coronary stenting versus balloon angioplasty as a rescue intervention
after failed thrombolysis in patients with acute myocardial infarction. J
Am Coll Cardiol. 2004; 44 :2073-2079.
5. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. High
clopidogrel loading dose during coronary stenting: effects on drug
response and interindividual variability. Eur Heart J. 2004; 25: 1903-1910.
Dr Osman and colleagues are, of course, correct in their comments
regarding the evolving nature of percutaneous coronary intervention (PCI)
for acute myocardial infarction. However, their comment that the low use
of coronary stents, glycoprotein IIb/IIIa inhibition and thienopyridines
is likely to have influenced the outcome of our study, and hence our
conclusion, is not substantiated by either our...
Dr Osman and colleagues are, of course, correct in their comments
regarding the evolving nature of percutaneous coronary intervention (PCI)
for acute myocardial infarction. However, their comment that the low use
of coronary stents, glycoprotein IIb/IIIa inhibition and thienopyridines
is likely to have influenced the outcome of our study, and hence our
conclusion, is not substantiated by either our own data [1] or by data
from other contemporary trials of infarct angioplasty.
Firstly, plain balloon angioplasty (without stent implantation) was
not associated with hospital mortality in our study and neither was lack
of treatment with a thienopyridine (both of these variables of course
describe the same patient group). PCI without abciximab was also not
associated with hospital mortality. The only univariate or multivariate
predictors of hospital mortality were those described in the manuscript.
Secondly, Osman et al. refer to "outcomes" when our study is based on
survival in particular. Although stenting confers some advantage, there is
currently no evidence that it improves the chance of survival. In the
stent-PAMI (Primary Angioplasty in Myocardial Infarction) trial [2], there
was no reduction in one month mortality in the group receiving coronary
stent(s) compared to those receiving angioplasty alone. In fact,
numerically more patients died in the stent arm by one month of follow up
(3.5% versus 1.8%, p=0.15). The only significant difference in one month
outcomes was in a reduction in target vessel revascularisation in the
stent arm (1.3% versus 3.8%, p=0.02). Despite this, there was no
difference in the incidence of the combined clinical endpoint of death,
reinfarction, disabling stroke or target vessel revascularisation at one
month. By six months, the incidence of this composite (primary endpoint)
was lower in the stent arm (12.6% versus 20.1%, p<_0.01 almost="almost" exclusively="exclusively" due="due" to="to" less="less" target="target" revascularisation="revascularisation" in="in" the="the" stent="stent" arm="arm" _7.7="_7.7" versus="versus" _17.0="_17.0" p0.001="p0.001" and="and" with="with" a="a" persistent="persistent" numeric="numeric" excess="excess" of="of" deaths="deaths" _4.2="_4.2" _2.7="_2.7" p="p" similarly="similarly" cadillac="cadillac" comparison="comparison" angioplasty="angioplasty" stenting="stenting" or="or" without="without" abciximab="abciximab" acute="acute" myocardial="myocardial" infarction="infarction" trial="trial" _3="_3" incidence="incidence" _30="_30" day="day" mortality="mortality" each="each" four="four" groups="groups" balloon="balloon" alone="alone" was="was" statistically="statistically" same.="same." fact="fact" numerically="numerically" more="more" patients="patients" died="died" _="_" than="than" arm.="arm." these="these" trials="trials" were="were" not="not" powered="powered" detect="detect" early="early" differences="differences" mortality.="mortality."/> Thirdly, the ADMIRAL (Abciximab before Direct Angioplasty and
Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up)
trial [4] in which patients with STEMI were randomised to receive
abciximab or placebo prior to primary angioplasty with stenting,
demonstrated a statistically significant difference in the incidence of
the primary composite endpoint of death, reinfarction, or urgent
revascularization of the target vessel at 30 days favouring the abciximab
arm (6% versus 14.6%, p=0.01). The trial did not (and could not, because
of inadequate power) demonstrate a reduction in mortality at 30 days.
Similarly, although Osman cites the trial by Brener et al. [5] for showing
clear benefit with the addition of glycoprotein IIb/IIIa inhibition, we
must be clear about exactly what those benefits were. There was no benefit
in terms of 30 day mortality, nor was there a reduction in the incidence
of reinfarction by 30 days. The principle benefit seen by 30 days was a
reduction in the incidence in urgent target vessel revascularisation.
Fourthly, there are no data in the current literature to indicate
that the addition of a thienopyridine prior to or after primary PCI for
STEMI, in any dose, has any effect on early mortality. The CREDO
(Clopidogrel for the Reduction of Events during Observation) trial [6]
provides some information on the addition of clopidogrel in patients
undergoing contemporary PCI, but these were not patients with STEMI and
they were certainly not in cardiogenic shock. There was no statistically
significant reduction at 28 days in the incidence of death, MI or target
vessel revascularisation in the clopidogrel group compared to placebo
(6.8% versus 8.3%, p=0.23) and certainly no mortality benefit. Even
amongst those receiving clopidogrel loading more than 6hrs before
intervention, there was no significant reduction in mortality. Arbitrarily
delaying intervention in cardiogenic shock for such a weak benefit could
hardly be justified and none of the patients we treated who were referred
from other centres took six hours from referral to the time of
angioplasty. It is doubtful whether the paper by Angiolillo et al. [7], in
which 50 patients with stable coronary artery disease undergoing elective
PCI were randomised to receive either 300mg or 600mg of clopidogrel prior
to PCI and underwent assessment of platelet aggregation and activation, is
relevant to the current discussion.
The principle point of interest in our study is whether the presence
of particular patient characteristics can be used to determine the
likelihood of the natural history of cardiogenic shock complicating acute
myocardial infarction being altered by emergency transfer and attempted
PCI. Once a catheter-based revascularisation strategy is started, there is
very little evidence that procedural or pharmacological "niceties" play a
significant role in affecting hospital mortality. Although current
patients are likely to receive stents as well as additional anti-platelet
agents, we should be clear about what is known and what is not known about
these strategies.
AGC Sutton, MA de Belder
References
1. Sutton AGC, Finn P, Hall JA et al. Predictors of outcome after
percutaneous treatment for cardiogenic shock. Heart 2005; 91: 339-344.
2. Grines CL, Cox DA, Stone GW et al. Coronary angioplasty with or
without stent implantation for acute myocardial infarction. N Eng J Med
1999;341:1949-56.
3. Stone GW, Grines CL, Cox DA et al. Comparison of angioplasty with
stenting, with or without abciximab, in acute myocardial infarction. N Eng
J Med 2002;346:957-66.
4. Montalescot G, Barragan P, Wittenberg O et al. Platelet
glycoprotein IIb/IIIa inhibition with coronary stenting for acute
myocardial infarction. N Eng J Med 2001;344:1895-903.
5. Brener SJ, Barr LA, Burchenal JEB et al. Randomized, placebo-
controlled trial of platelet glycoprotein IIb/IIIa blockade with primary
angioplasty for acute myocardial infarction. Circulation 1998; 98: 734-
741.
6. Steinhubl SR, Berger PB, Mann JT et al. Early and sustained dual oral
antiplatelet therapy following percutaneous coronary intervention. JAMA
2002; 288(19):2411-20.
7. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. High
clopidogrel loading dose during coronary stenting: effects on drug
response and interindividual variability. Eur Heart J 2004;25:1903-1910.
Cardioembolic stroke according to many data available is one of the
major killers in cerebrovascular diseases. When age-adjusted to the
European population cardioembolism have the highest incidence rates,
higher case fatalities as well as recurrence rates [1].
The (under)use of oral anticoagulants in AF subjects is the cornerstone of
many guidelines [2,4].
Cardioembolic stroke according to many data available is one of the
major killers in cerebrovascular diseases. When age-adjusted to the
European population cardioembolism have the highest incidence rates,
higher case fatalities as well as recurrence rates [1].
The (under)use of oral anticoagulants in AF subjects is the cornerstone of
many guidelines [2,4].
According to the latest available World Survey of Cardiac Pacing report,
despite health care authorities budget reductions, the total amount of PM
implants increased worldwide. Taking into account data regarding EU and US
more than 7.000 PMs in 1997 were implanted. In 2001 over the same
countries involved in the project, more than 9.000 devices were positioned
[5].
Whether dual or single chamber ventricular pacing may have different
relevance over AF recognition, and subsequent stroke risk, have already
been focused [6].
The recent publication of the long term survey on PM patients performed at
Queen Mary Hospital of Hong Kong by Tse made evident that thousands of
normal dwelling PMs patients may have unrecognised AF episodes, not
receiving any adequate antithrombotic prophylaxis [7].
Thus hundreds of potentially preventable ischemic events occur.
Tse showed at baseline how the 28% of AF patients were under oral
anticoagulants, while at the follow up visits such percentage raised to
49%. There were other reasons for not administering anticoagulants ? How
many patients were under aspirin or other antithrombotics ?
In our opinion both new onset AF and contraindications can account only
for a minority of non-prescriptions [6].
Stroke prevention in PM patients can be further optimised: this subjects
are under close follow up, cardiac rhythm can be checked with feasible
procedures thus guidelines needs to be better attended.
We strongly believe that a closer cooperation of cardiologist and the
stroke neurologist is mandatory for implementing strategies to reduce the
burden of stroke.
References
1. Kolominsky-Rabas L, Weber M; Gefeller O; Neundoerfer B, Heuschmann
P Epidemiology of Ischemic Stroke Subtypes According to TOAST Criteria.
Stroke. 2001;32:2735
2. Deplanque D, Corea F, Arquizan C, Parnetti L, Mas JL, Gallai V,
Leys D. Stroke and atrial fibrillation: is stroke prevention treatment
appropriate beforehand? SAFE I Study investigators.Heart. 1999
Nov;82(5):563-9.
3. Deplanque D, Leys D, Parnetti L, Schmidt R, Ferro J, De Reuck J,
Mas JL, Gallai V; SAFE II Investigators. Stroke prevention and atrial
fibrillation: reasons leading to an inappropriate management. Main results
of the SAFE II study. Br J Clin Pharmacol. 2004 Jun;57(6):798-806.
4. Bornstein N, Corea F, Galllai V, Parnetti L. Heart-brain
relationship: atrial fibrillation and stroke. Clin Exp Hypertens. 2002 Oct
-Nov;24(7-8):493-9.
5. Mond HG, Irwin M, Morillo C, Ector H. The world survey of cardiac
pacing and cardioverter defibrillators: calendar year 2001. Pacing Clin
Electrophysiol. 2004 Jul;27(7):955-64.
6. Patel AM, Westveer DC, Man KC, Stewart JR, Frumin HI. Treatment of
underlying atrial fibrillation: paced rhythm obscures recognition. J Am
Coll Cardiol. 2000,Sep;36(3):784-7.
7. Tse HF, Lau CP. Prevalence and clinical implications of atrial
fibrillation episodes detected by pacemaker in patients with sick sinus
syndrome. Heart. 2005 Mar;91(3):362-4.
Dear Editor,
It would seem that the K+(atp) channel opener pinacidil and closer glibenclamide might exert their effects by deceasing and increasing respecitively the rates of ATP resynthesis [1,2]. The implication is that the primary determinants of ATP resynthesis, pH, substrate availability for oxidative phosphorylation and body temperature, are important determinants of the degree of H+(atp) channel openess a...
Dear Editor,
As cardiac surgeons we read and reread the editorial by Ashrafian and Bogle initially with interest and subsequently bemusement looking for a definitive message. The title was clear enough; the editorial was not.
The conclusion that good practice will be served if “patients are adequately counselled on the benefits of good dental hygiene and a discussion is undertaken and documented on the ri...
Dear Editor,
The editorial by Ashrafian and Bogle[1] suggests that the authors have little clinical experience in the management of patients with infective endocarditis (IE). The body of cardiologists and cardiac surgeons in Europe, North America and the UK would disagree that the BSAC guidelines are important or “a step in the right direction” and almost certainly the guidelines will be disregarded by the rest o...
Dear Editor,
In the report by Ashrafian1 and Bogle, the authors highlight new recommendations by the British Society for Antimicrobial Chemotherapy to limit prophylaxis to high-risk patients with previously documented endocarditis or surgical shunt/valve procedures (1). Although dental prophylaxis have an impact on systemic disease, they do not eliminate bacteremia altogether. Thus, in addition to antibiotic the...
Dear Editor,
The debate on the role of antimicrobial prophylaxis to prevent infective endocarditis (IE) has intensified as a consequence of the recently published guidelines from the Working Party of the British Society for Antimicrobial Chemotherapy (BSAC). In the review by Ashrafian and Bogle, reference is made to the dental community’s satisfaction with these new guidelines, highlighting a “victory for scien...
Dear Editor,
We have read with great interest the article by Roudaut et al entitled "Thrombosis of prosthetic heart valves: Diagnosis and therapeutic considerations" published in the last issue of your journal.(1) According to the authors, the first therapeutic consideration in obstructive left-sided prosthetic valve thrombosis (PVT) should be surgery and thrombolysis should be reserved for patients with contrain...
Dear Editor,
With interest we read the paper by Lofiego et al. on a long-term follow-up of 65 patients with left ventricular hypertrabeculation/noncompaction (LVHT).[1] We want to add some points and raise some concerns: The prevalence of neuromuscular disorders (NMDs) among patients with LVHT has been reported to be up to 82%.[2] The low rate of 9% in the presented study may be attributed to the fact that the pat...
Dear Editor,
We read with interest the article by Sutton et al. entitled ‘Predictors of outcome after percutaneous treatment for cardiogenic shock.’ [1]. We would like to congratulate the authors on attempting to identify risk factors that predict outcome in patients with cardiogenic shock who undergo percutaneous coronary intervention (PCI). We would, however, like to make a few points regarding the study that...
Dear Editor,
Dr Osman and colleagues are, of course, correct in their comments regarding the evolving nature of percutaneous coronary intervention (PCI) for acute myocardial infarction. However, their comment that the low use of coronary stents, glycoprotein IIb/IIIa inhibition and thienopyridines is likely to have influenced the outcome of our study, and hence our conclusion, is not substantiated by either our...
Dear Editor,
Cardioembolic stroke according to many data available is one of the major killers in cerebrovascular diseases. When age-adjusted to the European population cardioembolism have the highest incidence rates, higher case fatalities as well as recurrence rates [1]. The (under)use of oral anticoagulants in AF subjects is the cornerstone of many guidelines [2,4].
According to the latest available Wo...
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