We read the case report by Elliott et al (1) with great interest and would like to add to their findings. In three of five consecutive patients undergoing percutaneous septal ablation (PTSMA) for hypertrophic cardiomyopathy (HCM) they observed left ventricular cavity opacification during selective injection of the first septal perforator with the contrast agent Optison.

We treated a 61 year old man with a long history of HCM and limiting breathlessness depsite maximal medical therapy with PTSMA. His peak resting intraventricular gradient, measured using a double -lumen pitail catheter, was 134 mmHg with a post-ectopic gradient of 165 mmHg. With a 2.0 by 20 mm balloon inflated, initial injection of the echocardiographic contrast agent Levovist (Schering AG, Germany) selectively into the first septal perforator showed opacification of the basal septum as demonstrated on transoesophageal echocardiography. Using appropriate technical considerations 2.5 ml of alcohol was then injected into this artery. The ballon was left inflated in the septal perforator for 15 minutes and subsequently deflated. Following this the resting gradient was negligible but a peak provokable gradient of 105 mmHg was obtained. In view of this further ablation was planned and the adjacent second septal perforator was selectively instrumented. Levovist injection into this artery however resulted in echocardiographic enhancement of the mid septum distal to the site of flow acceleration.It was therefore decided not to proceed further with this artery and we returned to the original septal perforator. Repeat echocardiographic contrast injection through a shorter balloon (2.0 by 15mm) produced clear opacification of the left ventricular cavity.

In view of the safety considerations raised by Elliott el al (1)regarding the sytemic effects of alcohol we elected not to proceed further with the procedure. This case adds to the findings documented previously (1). It demonstrates that this phenomenon occurs with both Optison and Levovist contrast agents. The mechanism however is not clear although a number of possibilities are raised by Elliott et al (1). Interestingly in our patient left ventricular opacification occurred only after the first alcohol injection whereas in those cases discussed previously opacification occurred prior to alcohol injection. This could relate to our subsequent choice of a shorter balloon (the same size as used in the cases described by Elliott et al (1)) which may increase the number of septal sub-branches exposed to the contrast agent. Alternatively it may relate to the toxic effects of alcohol on the vasculature.

Mechanisms aside, our findings and those documented previously suggest that caution may be appropriate for the injection of alcohol where this phenomenon is observed.

1 Elliott PM, Brecker SJ, McKenna WJ. Left ventricular opacification during selective intracoronary injection of echocardiographic contrast in patients with hypertrophic cardiomyopathy. Heart 2000;83:e7

I enjoyed reading the recent article on the worldwide perspective of valve disease by Soler-Soler and Galve from Barcelona, Spain.[1] But I was surprised that no mention was made of mitral valve prolapse (MVP) anywhere in their article.

MVP is the commonest valve disorder in the United States as well as in many parts of the world.[2] It also has a prevalence of 4.3% in Spain (see table).

Prevalence (%) of mitral valve prolapse
 
 

Modified from reference 2.
*Echocardiographic study; **Necropsy study; ***Expressed as a ratio.

MVP is the commonest cause of mitral regurgitation in the United States and other developed countries[3] [4] as well as in the developing countries such as China.[5] [6] One of the serious complications of mitral regurgitation is atrial fibrillation which usually persists even after successful corrective surgery of the mitral valve and often recurs after pharmacologic or electric cardioversion.[7] Although postoperative atrial fibrillation can be successfully managed by antiarrhythmic drugs and long-term anticoagulant therapy to prevent thromboembolism, these therapeutic modalities are not without side-effects, torsades de pointes and bleeding, respectively. However, it was gratifying that the adjunctive use of the Cox maze procedure reported recently from the Mayo clinic increased the restoration of sinus rhythm to 82% of their patients.[8]

MVP is also the commonest cause of infective endocarditis.[9][10][11] The microbial agents causing infective endocarditis on prolapsing mitral valve are similar to those that infect valves deformed by congenital or rheumatic processes.[12] Although streptococci viridans are the most common organisms, coagulase-negative staphylococcal endocarditis is not an infrequent occurrence in patients with MVP. Recognition of the occurrence of endocarditis due to coagulase-negative staphylococci in patients with MVP is important for several reasons. First, blood cultures positive for these organisms are frequently disregarded in patients without prosthetic heart valves or intravascular catheters. Second, the indolent course of some coagulase-negative staphylococcal endocarditis may delay consideration of the correct diagnosis, particularly in patients without congenital or rheumatic heart disease. Finally, even with effective antimicrobial therapy on the basis of in vitro studies, the clinical course may be prolonged and characterized by multiple responses to and relapses following drug withdrawal.

Thus it was most unfortunate that such an important valve disease as MVP was inadvertently omitted from discussion in this otherwise comprehensive review of the subject.[1]

Tsung O. Cheng, M.D.
Professor of Medicine
Division of Cardiology
The George Washington University Medical Center
2150 Pennsylvania Avenue, N.W.
Washington, DC 20037, USA

References

1. Soler-Soler J, Galve E: Worldwide perspective of valve disease. Heart 2000;83:721-725.

2. Cheng TO, Barlow JB: Mitral leaflet billowing and prolapse. Its prevalence around the world. Angiology 1989;40:77-87.

3. Cheng TO: Mitral valve prolapse: an overview. J Cardiol 1989;19 (Suppl 21):3-20.

4. Danielsen R, Nordrehaug JE, Vik-Mo H: High occurrence of mitral valve prolapse in cardiac catheterization patients with pure isolated mitral regurgitation. Acta Med Scand 1987;221:33-38.

5. Zhou LY, Hu RD: Floppy valve syndrome: a clinicopathological analysis of 16 cases. Chin J Intern Med 1986;25:149-151.

6. Cheng TO: Mitral valve prolapse. A review. Chin J Intern Med 1988;27:56-60, 126-129.

7. Cheng TO: Combined mitral valve repair and the Cox maze procedure for mitral valve prolapse and regurgitation and associated atrial fibrillation. J Thorac Cardiovasc Surg 2000;119:634.

8. Handa N, Schaff HV, Morris JJ, Anderson BJ, Kopecky SL, Enriquez-Sarano M: Outcome of valve repair and the Cox maze procedure for mitral regurgitation and associated atrial fibrillation. J Thorac Cardiovasc Surg 1999;118:628-635.

9. McKinsey DS, Ratts TE, Bisno AL: Underlying cardiac lesions in adults with infective endocarditis. The changing spectrum. Am J Med 1987;82:681-688.

10. Atkinson JB, Virmani R: Infective endocarditis: changing trends and general approach for examination. Hum Pathol 1987;18:603-608.

11. Baddour LM, Bisno AL: Infective endocarditis complicating mitral valve prolapse: epidemiologic, clinical, and microbiologic aspects. Rev Infect Dis 1986;8:117-137.

12. Barlow JB, Cheng TO: Mitral valve billowing and prolapse. In: Cheng TO: The International Textbook of Cardiology. New York: Pergamon Press, 1987:497-524.

Cowie's editorial envisages a clinical role for measurement of brain natriuretic peptide (BNP) in the near future.[1] However, while the potential for risk stratification and monitoring of treatment in patients with heart failure is encouraging, we would urge caution regarding the diagnostic utility of plasma BNP concentration.

There is little doubt that the diagnosis of heart failure is difficult - only about a third of patients referred for echocardiography or to a cardiology clinic with suspected heart failure turn out to have left ventricular systolic dysfunction.[2, 3] Nor is there any doubt that a definitive diagnosis is important, as the institution of appropriate treatments may have a significant impact on survival as well as symptoms, while exclusion of left ventricular systolic dysfunction as a cause of symptoms allows other investigations and treatment to be planned. However, many echocardiography departments are becoming overwhelmed. Thus a simple test that can "rule in" or "rule out" left ventricular systolic dysfunction has considerable appeal.

In the assessment of any diagnostic test, it is useful to consider both the properties of the test (sensitivity and specificity) and the baseline probability of the diagnosis (ie, the probability before the test result is known). The use of decision analysis, based upon Bayesian statistics is invaluable in this regard and is recommended in standard textbooks of evidence-based medicine.[4]

Plasma natriuretic peptides are highly sensitive (over 90%) but only moderately specific (approximately 60%) tests for left ventricular systolic dysfunction.[5] As a consequence low plasma concentrations of natriuretic peptides will be helpful in "ruling out" the diagnosis of left ventricular systolic dysfunction but high concentrations will be of little value as they may be associated with a number of other diagnoses.[1] Hence, while plasma BNP concentrations will be very helpful in screening large numbers of patients where the overall prevalence of left ventricular systolic dysfunction is low,[5] their use in the investigation of patients with suspected heart failure will be much more limited.

In a study of patients referred to outpatients with suspected heart failure, we found that 15% of those with a normal plasma brain natriuretic peptide concentration had left ventricular systolic dysfunction.[3]

A further important question is whether BNP provides additional information aborve and beyond that given by current investigations. In our study, the use of plasma BNP concentration did not add significantly to more simple "tests" - a history of previous myocardial infarction and an electrocardiogram.[3] While history and an electrocardiogram are mainstays of the investigation of the breathless patient, a false negative rate for plasma BNP concentration of approximately 15% is too high to obviate the need for echocardiography in such individuals.

We believe that in the setting of patients with "suspected heart failure", an echocardiogram rather than plasma brain natriuretic peptide concentration remains the investigation of choice. Despite the exciting potential for estimating prognosis and adjusting treatment, there is currently no role for measurement of brain natriuretic peptide in routine clinical practice.

References

(1) Cowie MR. BNP: soon to become a routine measure in the care of patients with heart failure? Heart 2000:83:617-18.

(2) Francis CM, Caruana L, Kearney P, et al. Open access echocardiography in management of heart failure in the community. BMJ 1995;310:634-6.

(3) Landray MJ, Lehman R, Arnold IR. Measuring brain natriuretic peptide in suspected left ventricular systolic dysfunction in general practice: cross-sectional study. BMJ 2000;320:985-6.

(4) Sackett DL, Richardson WS, Rosenberg W, Haynes RB. Evidence-based medicine. How to practice and teach EBM. Churchill Livingstone 1998:118-28.

(5) McDonagh TA, Robb SD, Murdoch DR, et al. Biochemical detection of left- ventricular systolic dysfunction. Lancet 1998;351:9-13.

Martin J Landray
Lecturer in Medicine
University of Birmingham
Birmingham B15 2TH, UK

Richard Lehman
General Practice Principal
Hightown Surgery
Banbury OX16 9DB, UK

Ian Arnold
Consultant Cardiologist
Horton Hospital
Oxford Radcliffe Hospitals NHS Trust
Banbury OX16 9AL, UK

The recent article by Ghuran and Nolan is a valuable review about cardiovascular effects of recreational drugs.[1] We would like to provide additional information, not included in the review, about the induction of changes in the QT interval by some recreational substances.

The long QT syndrome has been associated with the occurrence of ventricular tachyarrhythmias (torsades de pointes). Considering the substances of abuse, to our knowledge, at least cocaine, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and alcohol[2] can induce changes in the QT/QTc interval. There are published clinical case reports describing this kind of change for MDMA,[3, 4] and for cocaine it has also been described the presence of torsades de pointes in a patient with idiopathic long QT syndrome.[5]

In addition we would like to present results of the ECG-recording obtained during a clinical trial where MDMA was administered. Eight healthy male recreational users of MDMA participated in a randomized, double blind, cross-over and placebo controlled study. All subjects received, in different experimental sessions, a single oral dose of placebo, MDMA 125 mg; MDMA 75 mg and d,l-amphetamine 40 mg. A 12 lead-electrocardiogram (50 mm/sec) was performed prior treatment (baseline measure) and 1, 2, 4, 8 and 24 hours after drug administration. Cycle length (RR) and QT interval were measured manually by the same blinded investigator. Both measures were performed in all 12 leads of each ECG recording. Corrected QT was calculated with Bazett's formula. Interlead QTc dispersion was determined as the longest minus the shortest QTc on the 12-lead ECG. Changes in the T wave and appearance of U waves were also considered. Individual changes after each treatment conditions were evaluated according to criteria suggested by the Committee for Proprietary Medicinal Products (CPMP).[6] Other details of the trial have been previously published.[7] The table shows the number of subjects (maximal 8) who fulfil any criteria for prolonged cardiac repolarisation:

Mean QTc values (ms; n = 8) for each administered substance
 

*Following CPMP criteria

The maximal effects were observed two hours after MDMA administration and returned to normal values at 4-8 hours. For amphetamine the maximal effects were observed lately, 8 to 24 hours after drug administration. Although the magnitude of mean QTc increase was not clinically relevant, individual data of some subjects might be interpreted as important "warning" signs of possible malignant arrhythmia in accordance to the CPMP recommendation. The mean QTc increase observed for MDMA is similar to that described after the administration of therapeutic doses of prescription drugs as terfenadine or cisapride in clinical trials.

The administration of a single oral dose of MDMA, in the range of those consumed recreationally, produce a slight increase of QTc. Although these changes are mild in magnitude, MDMA could enhance the risk of ventricular arrhytmia in subjects with genetic predisposition to present an acquired long QT syndrome, and/or when used in combination with other well known arrhythmogenic drugs.

Supported by grants FIS 97/1198, CIRIT 1997SGR00077, ISC-III-97/4344 and Plan Nacional sobre Drogas (Madrid).

Magí Farré
Marta Mas
Lluis Molina
Jordi Camí
Units of Pharmacology and Cardiology
IMIM-Hospital del Mar, UAB - UPF
Barcelona, Spain

References

(1) Ghuran A, Nolan J. Recreational drug misuse: issues for the cardiologist. Heart 2000;83:627-33.

(2) Rossinen J, Sinisalo J, Partanen J, et al. Efects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls. Clin Cardiol 1999;22:591-4.

(3) Maxwell DL, Polkey MI, Henry JA. Hyponatremia and catatonic stupor after taking "ecstasy". BMJ 1993;307:1399.

(4) Drake WM, Broadhurst PA. QT-interval prolongation with ecstasy. S Afr Med J 1996;86:180-1.

(5) Schrem SS, Belsky P, Schwartzman D, et al. Cocaine-induced torsades de pointes in a patient with the idiopathic long QT syndrome. Am Heart J 1990;120:980-4.

(6) Committee for Proprietary Medicinal Products (CPMP). The assessment of the potential for QT interval prolongation by non-cardiovascular medicinal products. London: Commission of the European Communities, 1997 (Available from URL: http://www.eudra.org/en_home.htm).

(7) Mas M, Farré M, de la Torre R, et al. Cardiovascular and neuroendocrine effects, and pharmacokinetics of MDMA in humans. J Pharmacol Exp Ther 1999;290:136-45.