Dear Editor,

We read with interest Bellenger et als description of the determination of fractional flow reserve (FFR) to guide treatment of side branch arteries following provisional stenting across a bifurcation. The use of pressure wires to guide treatment of main vessel narrowings (1) and ambigious stenoses in multi-vessel disease (2) and ACS (3) is established.

Based on their preliminary findings, that there is a poor correlation between the angiographic degree of nipping by quantitative coronary angiography (QCA) and the FFR in the side branches after stenting the main vessel, the authors called for a randomised controlled trial to determine whether FFR-directed treatment of side branch nipping improves clinical and angiographic outcome following PCI at bifurcations.

Given that such side branches may be relatively small (2.3 +/-0.2mm in the current study) we question the assertion that a QCA stenosis >50% would trigger treatment by many interventionists. FFR determination encompasses the interaction between the degree of anatomic stenosis and the area of myocardium perfused by the vessel.

This goes some way in accounting for the occurrence of haemodynamically significant obstruction in only a minority of vessels (3/14) in the current study. Indeed others have shown that in larger side branches (> 2.5mm) where QCA-assessed stenosis is >75% following main vessel stenting, a greater proportion will demonstrate functional significance (38% vs 27% in vessels < 2.5mm), although the overall occurrence of functionally significant stenoses remains small (4). Further, were treatment of the side branch to be undertaken, it is as likely to involve POBA as a second stent procedure (5). The authors own findings would suggest that a strategy of treating only the main vessel is sufficient, achieving a "functionally adequate result" in the majority of cases (79%). Therefore the extra cost incurred by routine use of a pressure wire in this situation might prove difficult to justify if, as the authors concur, the likelihood of a functionally significant lesion is "infrequent". In their small pilot study, none of the lesions measuring less than 50% by QCA were associated with a FFR less than 0.75.

Undoubtedly deferring treatment of side branches will prevent unnecessary coronary interventions and their related complications - whether routine use of a pressure wire is required to achieve this is debateable.

References

1. Bech GJW, De Bruyne B, Pijls NHJ, et al.
Fractional Flow Reserve to Determine the Appropriateness of Angioplasty in Moderate Coronary Stenosis : A Randomized Trial.
Circulation. 2001; 103(24):2928-2934.

2. Berger A, Botman K-J, MacCarthy PA, et al.
Long-Term Clinical Outcome After Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease.
JACC. 2005; 46(3):438-442.

3. Joshua J. Fischer X.
Outcome of patients with acute coronary syndromes and moderate coronary lesions undergoing deferral of revascularization based on fractional flow reserve assessment.
Catheterization and Cardiovascular Interventions. 2006; 68(4):544-548.

4. Koo B-K, Kang H-J, Youn T-J, et al.
Physiologic Assessment of Jailed Side Branch Lesions Using Fractional Flow Reserve.
JACC. 2005; 46(4):633-637.

5. Pan M, de Lezo JS, Medina A, et al.
Rapamycin-eluting stents for the treatment of bifurcated coronary lesions: A randomized comparison of a simple versus complex strategy.
Am Heart J. 2004; 148(5):857-864.

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 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.

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 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

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 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.