july-august 2004

A NNALS OF S AUDI M EDICINE Vol. 24 No. 4

July-August 2004 • Jumada Awal-Jumada Thani 1425

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A detail of “Oriental Melodies˜ (150 X 350 cm, oil on canvas) by Saudi artist Naiel Mulla. Mr. Mulla is co-founder of the Plastic Artists House and the Arabic Calligraphy Group in Jeddah. He has participated in more than fifty exhibitions in the Kingdom of Saudi Arabia and abroad. This work won a top prize in the Ambassadorˆs First Plastic Art Competition held in Riyadh in 2002. His work was provided by Mr. Saad Al-Showaiman of Sharqia Arts, Riyadh, Saudi Arabia.



INFORMATION FOR AUTHORS THE EDITORS of the Annals of Saudi Medicine welcome contributions from our readers. The Annals will consider for publication manuscripts of interest to readers in Saudi Arabia, the Middle East, and around the world. All submissions are subject to review by the Editorial Board and by referees in appropriate specialties. Submission of Manuscripts Manuscripts are received with the understanding that they are not under simultaneous consideration by another publication. An abstract published prior to a full report is not regarded as a duplicate publication. The author’s transmittal letter must accompany the manuscript and contain these statements: “The manuscript has been seen and approved by all authors involved and is neither being published nor being considered for publication elsewhere. The authors transfer copyright to the Annals of Saudi Medicine.” Accepted manuscripts may not be published elsewhere without Annals’ permission. The author should also include the names and addresses of four possible referees who are specialists in the field covered by the manuscript, and who do not work at the author’s institution. Manuscript Preparation The format of the Annals of Saudi Medicine complies with “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” published by the International Committee of Medical Journal Editors in Vancouver, British Columbia, in 1979 (the widely accepted “Vancouver style”), as described in the Annals of Internal Medicine (1997;126:36-47). With the exception of blood pressure, all units of measurement and laboratory values must be expressed in SI units; conventional units may be included parenthetically. Authors are referred to Annals of Internal Medicine (1987;106[1]:114-29) for guidance in the use of SI units. Manuscripts, including tables, references, and figure legends, must be typewritten, double-spaced, on 8 1/2 x 11 inch or size A4 paper, with margins of at least 1 inch. Pages should be numbered consecutively, beginning with the title page and continuing through the last page of typewritten material. One original and two photocopies of the entire manuscript should be submitted, along with three sets of photographs. Title Page. The title page must contain: 1) title of the article, 2) correct names of each author plus highest academic degree for each, 3) each author’s official academic and/or clinical title and affiliation, 4) name and address of the institution(s), 5) name and address (and e-mail), including telephone and fax numbers, of author to whom correspondence should be sent, if it differs from the first author, and 6) any disclaimers. For case reports, it is recommended that the number of authors be limited to four. Abstracts. All original articles must contain an abstract of not more than 250 words. The abstract should be divided into: Background, Patients(or Methods/Subjects) and Methods, Results, and Conclusion, and Key Words. Manuscript Format. Most original articles have the following format: Introduction (the question the paper intends to answer); Patients and Methods (the study design and methods, definitions such as for diagnostic criteria, the population or patient samples, and laboratory and statistical methods); Results (the pertinent findings in a logical sequence with tables and figures as necessary); and Discussion (conclusions based on the findings, evidence from the literature that supports the conclusions, conflicting evidence, applicability of the conclusions, and implications for future research or clinical applications). Authors might consult recent issues of

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Submit manuscripts online at http://mc.manuscriptcentral.com/kfshrc/asm


July-August 2004 • Jumada Awal-Jumada Thani1425

CONTENTS Editorial 240 The mobile angiograph in a center without on-site surgical back-up: the de facto standard? Walid Hassan, Suleiman Kharabsheh Special Communication 242 Recommendations for the diagnosis and management of osteoporosis: A local perspective Hussein Raef, Husn H. Frayha, Mohamed El-Shaker, Abdulla Al-Humaidan, Walter Conca, Ulla Sieck, Janine Okane Original Articles 253 Three years of experience with a mobile angiograph in a center without on-site surgical back-up Ramazan Akdemir, Hakan Ozhan, Mehmet Yazici, Huseyin Gunduz, Enver Erbilen, Sinan Albayrak, Cihangir Uyan 259 Magnesium decreases cardiac ınjury ın patients undergoing coronary artery bypass surgery Adem Grbolar Resatoglu, Orhan Saim Demirturk, Nuran Yener, Ali Yener 262 Antenatal screening for syphilis in a tertiary care hospital in Riyadh Zahid Shakoor 265 Screening of pregnant Saudi women for hepatitis B surface antigen Yagob Y. Al-Mazrou, Mohamed Al-Jeffri, Mohamed K.M.Khalil, Yasser S. Al-Ghamdi, Ameen Mishkhas, Mohamed Bakhsh, Mostafa Eisa, Mohamed Nageeb, Salah Tumsah 270 Emerging nalidixic acid and ciprofloxacin resistance in non-typhoidal Salmonella isolated from patients having acute diarrhoeal disease B.R.Panhotra, A.K.Saxena, Ali M.Al-Arabi Al-Ghamdi 273 Correlation of clinical presentation with intraoperative level diagnosis in lower lumbar disc herniation Hamed Reihani-Kermani 276 Vaginal birth following two cesarean deliveries—are the risks exaggerated? Vibha Kailash Garg, E. N. Ekuma-Nkama

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The effect of carbohydrate intolerance on neonatal birth weight in pregnant women without gestational diabetes mellitus Devrim Ertunc, Ekrem Tok, Umut Dilek, Özlem Pata, Saffet Dilek

284

Effect of obstructive airway disease in patients with noncystic fibrosis bronchiectasis Mohammed Khalid, Sarfraz Saleemi, Mohammed Zeitouni, Saleh Al Dammas, Muhammad Rehan Khaliq

288

What’s Your Diagnosis?

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Brief Reports Discoid lupus erythematosus in Iraqi patients: a clinical and histopathological study Mohammed Kadhim Al-Hattab, Makram Al-Waiz Histological changes in the lung of Wistar albino rats (Rattus norvegicus) after exposure to Arabian incense (Genus Boswellia) Majed S. Alokail, Saud A. Alarifi

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Case Reports Gastric duplication cyst Ruhul Amin Hassan

299

Rhinosporidiosis of the male urethra

Farukh Qureshi, Mahmoud S. Abdulmannan, Ali A. Eltayeb, Syed Qadri, Hussein Al-Qahtani, Ayman Gabr

301

Report of a rare co-incidence of congenital factor V deficiency and thalassemia intermedia in a family

Yasser Abou Mourad, Ali Shamseddine, Ayad Hamdan, Susane Koussa, Ali Taher

303

Letters

307

Answer to What’s your Diagnosis

310

Book Review

311

News

315

Announcements

316

Links for Authors

317

Arabic Abstracts



ORIGINAL ARTICLES IN THIS ISSUE

CARDIOLOGY Three years of experience with a mobile angiograph in a center without on-site surgical back-up In a retrospective review of 1485 coronary angiograms and 172 percutaneous coronary interventions using a mobile angiograph, Akdemir et al found that efficacy and safety were similar to data reported elsewhere. They conclude that diagnostic procedures and percutaneous coronary interventions can by safely performed with a mobile angiograph in centers without on-site surgical back-up. Magnesium decreases cardiac injury in patients undergoing coronary artery bypass surgery In a randomized, controlled study, Resatoglu et al found that the addition of magnesium to intermittent antegrade warm blood hyperkalemic cardioplegia in patients undergoing coronary artery bypass surgery resulted in a decrease in markers of cardiac myocardial injury. The data indicate that magnesium can be added to cardioplegic solutions to attenuate myocardial injury in patients undergoing cardiopulmonary bypass. INFECTIOUS DISEASE Antenatal screening for syphilis at a tertiary care hospital in Riyadh Of 3270 pregnant women tested by the rapid plasma reagin test at King Khalid University Hospital, only one was found to have syphilis. Shakoor questions the need to continue routine antenatal syphilis screening in Saudi Arabia. Screening of pregnant Saudi women for hepatitis B surface antigen In a cross-sectional survey of 2664 pregnant Saudi women, AlMazrou et al found that the prevalence rate for HbsAg, the most important factor contributing to the high carrier rate in Saudi Arabia, was lower than in previously published data, but regional variation was prominent. The MOH strategy of giving the first dose of hepatitis B vaccine at birth should continue. Emerging nalidixic acid and ciprofloxacin resistance in nontyphoidal Salmonella isolated from patients having acute diarrhoeal disease Panhotra et al found that resistance to nalidixic acid and ciprofloxacin increased significantly from 1999 to 2002 in strains of non-typhoidal Salmonella isolated from fecal samples at King Fahad Hospital in Al-Hofuf. Their findings support the concern that use of quinolones in animal feed may lead to an increase in resistance and should be restricted.

NEUROSURGERY Correlation of clinical presentation with intraoperative level diagnosis in lower lumbar disk herniation In a prospective study, Reihani-Kermani found greater diagnostic value in the clinical features of fifth lumbar disc herniation than fourth lumbar disc herniation in the level diagnosis of lower lumbar disc herniation. Clinical presentation was highly specific but insensitive. OBSTETRICS AND GYNECOLOGY Vaginal birth following two cesarean deliveries—are the risks exaggerated? Garg et al report a lower rate of maternal complications and shorter hospital stay in women who had a normal vaginal delivery compared with women who had a cesarean delivery. Both groups had had two previous lower segment cesarean deliveries. The women who delivered vaginally were offered a trial of labor that was not induced or augmented at any stage. ENDOCRINOLOGY AND METABOLISM The effect of carbohydrate intolerance on neonatal birth weight in pregnant women without gestational diabetes mellitus Ertunc et al found an increased incidence of neonatal hypoglycemia and hyperbilirubinemia and a lower mean birth weight in babies of women without gestational diabetes who had a positive 50-g glucose challenge test, but a negative 100-g oral glucose tolerance test, compared with women who had a negative 50-g test. In this prospective study, all women had uncomplicated pregnancies and no risk factors for gestational diabetes mellitus according to ACOG criteria. These differences may reflect the effect of mild gestational glucose intolerance. PULMONOLOGY Effect of obstructive airway disease in patients with noncystic fibrosis bronchiectasis In a retrospective comparison of non-cystic fibrosis bronchiectasis patients with obstructive or non-obstructive airway disease, Khalid et al found that patients with obstructive airway disease had significantly greater Pseudomonas colonization, hypercapnic respiratory failure, and mean number of admissions due to exacerbation. Mortality was also higher in the patients with obstructive airway disease, but the difference was not statistically significant.

ARTICLEEDITORIAL TYPE GOES HERE

The mobile angiograph in a center without on-site surgical back-up: the de facto standard? Walid Hassan, MD, FCCP, FACP, FACC, FSCA&I; Suleiman Kharabsheh, MD

I

n 1976 Dr. Andreas Gruentzig started the era of percutaneous coronary intervention (PCI) with the first coronary artery balloon dilation. Since the introduction of percutaneous transluminal coronary angioplasty (PTCA) into clinical practice, authorities have recommended a surgical standby, i.e., prompt access to emergency surgery with cardiopulmonary bypass and a full operational team of anaesthesiologists, perfusionists and surgeons.1 However, major advances in recent years in devices and pharmaceutical therapy have dramatically reduced the incidence of urgent coronary artery bypass graft (CABG) surgery performed due to PTCA complications from 10% to 25% at the time of technique introduction to 2% to 5% in the late ‘80s, and 1% to 2% today.2,3 The main cause of death in patients undergoing PTCA is an abrupt arterial closure during or immediately after PTCA. This complication occurs in 3% to 8% of all procedures and may result from arterial wall dissection, clot formation blocking the blood flow in the vessel, arterial spasm and a sudden fall in blood pressure. Immediate restoration of blood flow is imperative for a patient’s survival. Initially, abrupt arterial closure was treated with urgent CABG. However in the ‘80s, prolonged perfusion balloon inflation became a common practice. With the introduction of the intracoronary stents in the ‘90s, most cases of abrupt vessel closure due to dissection can be successfully treated with cover stents for perforation.2 The optimization of antithrombotic treatment permits more effective prevention and treatment of platelet thrombi. The introduction of the high-pressure stent implantation technique and combined use of aspirin and Plavix (clopidogrel) or ticlopidine reduced the risk of acute and subacute thrombosis from 15% to less than 1%.4 The use of platelet glycoprotein IIb/IIIa receptor inhibitors permitted a further reduction in periprocedure complications and the need for urgent CABG.5 In patients with diminished left ventricular contractility or a large area of the myocardium supplied by the artery being dilated, acute vessel closure may lead to severe hemodynamic instability and cardiogenic shock. Intra-aortic balloon pump (IABP) support can stabilize the patient and improve myocardial blood supply, which increases angioplasty success or serves as a bridge to urgent surgical intervention. Several randomized trials and meta-analyses have proved the superiority of PCI over thrombolytic therapy for acute myocardial infarction (AMI), and recent trials also favor an early initial invasive strategy for the treatment of high-risk acute coronary syndrome (ACS) patients. However, on average

Ann Saudi Med 24(4) July-August 2004 www.kfshrc.edu.sa/annals

From the Department of Cardiovascular Diseases King Faisal Specialist Hospital & Research Centre Riyadh, Saudi Arabia Correspondence to: Dr. Walid Hassan Department of Cardiovascular Diseases - MBC 16 King Faisal Specialist Hospital & Research Centre P.O. Box 3354 Riyadh 11211 Saudi Arabia E-mail: [email protected] Accepted for publication: May 2004

two-thirds of AMI and ACS patients present to community hospitals that have no cardiac catheterization laboratory or no on-site cardiothoracic surgery backup available, which precludes doing PCI in most parts of the world at the present time because of the fear of procedural complications that would require immediate surgical bail out. The Atlantic Cardiovascular Patient Outcomes Research Team (C-PORT) trial,6 a prospective, randomized trial was conducted from July 1996 through December 1999 to determine whether treatment of acute MI with primary PCI is superior to thrombolytic therapy at hospitals without onsite cardiac surgery and, if so, whether superiority is durable. The study included 451 thrombolytic-eligible patients with an acute MI of less than 12 hours duration associated with ST-segment elevation on electrocardiogram. Patients were randomly assigned to receive primary PCI (n=225) or accelerated tissue plasminogen activator (bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5 mg/kg for 60 minutes; n=226). The primary end point was median hospital length of stay and the 6-month composite incidence of death, recurrent MI, and stroke. The incidence of the composite end point was reduced in the primary PCI group at 6 weeks (10.7% vs. 17.7%; P=.03) and 6 months (12.4% vs. 19.9%; P=.03) after index MI. Six-month rates for individual outcomes were 6.2% vs. 7.1% for death (P=.72), 5.3% vs. 10.6% for recurrent MI (P=.04), and 2.2% vs. 4.0% for stroke (P=.28) for primary PCI vs. thrombolytic therapy, respectively. Median length of stay was also reduced in the primary PCI group (4.5 vs. 6.0 days; P=.02). No patient in the primary PCI group was sent for emergen-

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MOBILE ANGIOGRAPH

Table 1. Rates of emergency bypass surgery and mortality for 54 379 patients undergoing percutaneous coronary intervention at hospitals with and without on-site cardiac surgery in France (62% of centers did not have cardiac surgery). 7 Centers with surgery

Centers without surgery

Emergency bypass surgery

0.44%

0.25%

Mortality

0.72%

0.41%

cy CABG surgery for a catheterization-related or PCI-related complication, including abrupt closure, dissection, or coronary perforation due to a complication at the index hospital. Sixtynine percent of the thrombolytic therapy group was transferred to a tertiary hospital for additional care, whereas 31% of the primary PCI treatment group was transferred (P=.002). No patient was transferred to a tertiary facility because of a complication of primary PCI. The mean door-to-balloon time was 105.2 minutes, which represents a treatment time at least as good as the average of 120 minutes reported at the lowest-mortality (highest-volume) institutions in the NRMI registry. Due to recent improvements in the safety of PTCA procedures, the indications for the procedure have been extended. At present PCI is performed in complex type C lesions, multivessel disease, LV dysfunction, and ACS. Despite the increased frequency of PTCA, the need for emergency CABG has been reduced to less than 1% at experienced centers with a high volume of procedures.2 For this reason, the number of centers worldwide that perform the PTCA without on-site surgical cover is increasing (in the USA alone, the range is 200-300 centers). The same applies to the Middle East, where the rising demand for interventional cardiac procedures has also caused an increase in the number of laboratories that perform PTCA without on-site surgical cover. Germany, France, and Italy have a long history of not requiring bypass surgery at centers that perform PCI. A large registry of over 50,000 patients undergoing intervention in France recently reported no differences in outcomes at centers with and without cardiac surgery, with less than 0.4% of patients References

1. Angelini P. Guidelines for surgical standby for coronary angioplasty: should they be changed? J Am Coll Cardiol. 1999; 33:1266-1268. 2. Seclwer J, Butte A, Harrell L, et al. Acute occlusion during coronary interventions: the changing pattern in era of stents. J Invas Cardiol. 1998; 10:208-212. 3. Topol EJ, Serruys PW. Frontiers in interventional cardiology. Circulation. 1998; 98: 1802-1820. 4. Schmig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996; 334:1084-1089. 5. EPISTENT Investigators. Randomized placebocontrolled and balloon angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Lancet. 352: 87-92. 6. Aversano T, Aversano LT, Passamani E, et al. Thrombolytic Therapy vs. Primary Percutaneous

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requiring emergency surgery; 0.44% of patients at surgical hospitals and 0.25% of patients at non-surgical hospitals were sent for emergency bypass.7 Two-thirds of the hospitals in this registry had no on-site surgical facilities. The mortality at surgical hospitals was 0.7%; at non-surgical hospitals it was only 0.4%. Thus the non-surgical hospitals in this very large registry sent fewer patients to emergency surgery and had fewer deaths! (Table 1). There are at least eight other registries of PCI without on-site surgery, located in Canada, the United Kingdom, Germany, and Italy.8-14 These report outcomes of an aggregate of over 70,000 patients undergoing non-emergent angioplasty at hospitals without in-house surgery. The overall mortality, pooling data from all of these series, was 0.48%. The article by Akdemir and colleagues in this issue of the Annals (page 265) provides some important insights and validation of the abovementioned approach. There were no major adverse cardiac events (MACE) during their diagnostic cardiac procedures. They performed advanced PCI using a mobile angiograph without on-site surgical cover in patients with a different spectrum of CAD, ranging from stable angina (20.9%), unstable angina (46.5%), acute MI (32.5%) to cardiogenic shock (6%), and despite their relatively small volume, they achieved a 96% success rate (using predilation technique) with no acute or subacute thrombosis and comparable MACE (mortality 1.2%, urgent CABG 1.8%, MI 1.2%). Six months of follow-up revealed a comparable binary restenosis and target vessel revascularization (18.1%). Dr. Akdemir and colleagues must be congratulated for their effort to validate this approach in our region. I hope it will be studied further in future large-scale trials with longer followup. Important prerequisites for successful implementation of this approach include proper training with appropriate patient and lesion risk characterization, a high volume of procedures, prompt access to equipment including different types of coronary stents, IABP, and a close liaison with the nearest cardiac surgical center, with effective transfer that would enable patients to be on cardiopulmonary bypass within 90 minutes.

Coronary Intervention for Myocardial Infarction in Patients Presenting to Hospitals Without On-site Cardiac Surgery: A Randomized Controlled Trial. JAMA. 2002;287:1943-1951. 7. Loubeyre C, Morice MC, Berzin B, et al. Emergency coronary artery bypass surgery following coronary angioplasty and stenting: results of a French multicenter registry. Cathet Cardiovasc Intervent. 1999; 48:441-448. 8. Klinke WP, Hui W. Percutaneous transluminal coronary angioplasty without on-site surgical facilities. Am J Cardiol. 1992; 770:1520-1525. 9. Reifart W, Schwarz F, Preusler W, Stoerger H, Hofmann M. Results of PTCA in more than 5,000 patients without surgical standby in the same center [abstract]. J Am Coll Cardiol. 1992; 19:229A. 10. Ribichini F, Uslenghi E, Picco L, et al. Electivecoronary angioplasty in total absence of heart surgery.

G Ital Cardiol. 1994;24:949-956. 11. Baduini G, Belli KR, de Benedicdtis M, et al. Coronary angioplasty in an Italian hospital without on-site cardiac surgery: the results and outlook [in Italian]. G Ital Cardiol. 1994;24:1529-1536. 12. Reifart N, Preusler W, Schwarz F, et al. A large center experience of coronary angioplasty without on-site surgical standby. In: Topol EJ, Serruys PW, eds. Current Review of Interventional Cardiology. 2nd ed. Philadelphia: Current Medicine;1995:296-303. 13. Dellavalle A, Steffenino G, Ribichini F, et al. Elective coronary angioplasty with and without surgical standby: clinical and angiography for the selection of patients. Coronary Artery Disease 1995;6: 513-520. 14. Vogt A, Bonzel T, Harmjanz D. PTCA registry of German community hospitals. Eur Ht J 1997; 18: 1110-1114.


SPECIAL COMMUNICATION

DIAGNOSIS AND MANAGEMENT OF OSTEOPOROSIS

Recommendations for The Diagnosis and Management of Osteoporosis: A Local Perspective The Osteoporosis Working Group, King Faisal Specialist Hospital and Research Center Hussein Raef, MD, FACP, FACE*; Husn H. Frayha, MD, FRCPC†; Mohamed El-Shaker, MD‡; Abdulla Al-Humaidan, PharmD**; Walter Conca,MD*; Ulla Sieck, MD¶; Janine Okane, MD‡

T

he subject of postmenopausal osteoporosis continues to be an important one for clinicians and epidemiologists, as the incidence of osteoporotic fracture continues to increase and the burden of such fractures on the health economy is expected to rise to astonishing figures. In the United States alone, 1.5 million osteoporotic fractures occur annually, with estimated direct expenditures of over $14 billion (American Association Of Clinical Endocrinologists guidelines). In the United Kingdom, 200 000 fractures per year are attributed to osteoporosis at an annual cost of over £940 million (Royal College Of Physicians guidelines). In Asia, the projected number of hip fractures is 3 million in the year 2050.1 Although these costs are considerable, the price of prevention and treatment for osteoporosis could be as high. Therefore, recommendations and guidelines for detection, screening, prevention and management of osteoporosis are obviously needed. A recent report by The US Preventive Services Task Force based on a review of evidence found that there is good reason for screening women for osteoporosis at age 65 and above, or between age 60 to 64 in the presence of significant fracture risk factors. This recommendation is in contrast to a previous recommendation made by the same task force against routine screening in 1997. Still there are no recommendations by the task force on screening younger postmenopausal women.2 A year 2000 consensus conference by NIH noted that the value of universal screening was not yet established. The National Osteoporosis Foundation and the American Association of Clinical Endocrinologists have made more liberal recommendations. Guidelines for prevention and treatment can also be controversial, especially when it comes to the level of bone mineral density (BMD) at which one would initiate prevention or treatment measures with pharmacological agents. Recent studies3,4 have shown an unexpected increased risk of cardiovascular events in postmenopausal women with the use of hormone replacement therapy (HRT). In addition, there was an increase in the risk of breast cancer and venous thrombosis. HRT has been regarded as a cornerstone, and often a first-line therapy, together with calcium, in the prevention and treatment of postmenopausal osteoporosis. Many women used this agent with the idea that it would also decrease cardiovascular risks. But the above


From the Departments of *Medicine, †Pediatrics, ‡Family Medicine and Polyclinics, **Pharmacy, and ¶Obstetrics and Gynecology, King Faisal Specialist Hospital & Research Center Riyadh, Saudi Arabia Correspondence to: Dr. Hussein Raef Department of Medicine, MBC 46 King Faisal Specialist Hospital & Research Centre P.O. Box 3354 Riyadh 11211 Kingdom of Saudi Arabia Email: [email protected] Accepted for publication: April 2004

findings have made it difficult to use HRT without accepting the risks involved. The value of newer pharmacological agents like bisphosphonates and selective estrogen receptor modulators (SERMs) have been established in treating postmenopausal osteoporosis, but their role in fracture prevention for subjects who are not osteoporotic has not been proven, although such therapy may prevent bone loss and improve BMD.5 It is clear therefore that practitioners need guidelines and recommendations for a rational and evidence-based approach to this problem. Such guidelines or recommendations should ideally be based on studies and projections made in the same population where these recommendation would be applied. Some of the factors that would influence these guidelines in a certain population are: 1) the incidence and the medical and financial impact of osteoporotic fractures in this population, 2) the prevalence of osteoporosis, especially among postmenopausal women, 3) the priority of osteoporosis compared to other public health issues in that society, 4) the cost-effectiveness of diagnostic, preventive and treatment measures, and 5) lifestyle factors and conditions that might impact the quality of bone or the risk of fracture in the young, postmenopausal women, and in the elderly (e.g., sun exposure, exercise, level of physical activity, chance of falling). Data on the prevalence of osteoporosis, rates of verte-

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bral and hip fractures, and the correlation of BMD and other fracture risk factors with fracture rates is generally sparse or lacking for Saudi Arabia, Gulf countries, and other Middle Eastern Arab countries. Nevertheless, certain deductions can be made from the available studies and personal observations: 1) BMDs are generally lower in the population of this region compared with the western population, with a higher percentage of young subjects and premenopausal women with osteopenia.6 However, a correlation between BMD and fracture rates has not been established in this region. 2) Fracture rates are lower than those reported in the west, but more than those reported in the Far East.7,8 Thus, using BMD parameters alone will likely result in unnecessary treatment and might not be cost effective. 3) Vitamin D deficiency is still a common problem in this region. There is an obvious need for local guidelines based on local data and experience. Local guidelines are not intended to replace the individual judgment needed for best use of the evidence while taking in account local and cultural factors. The recommendations in this document are based on a vast amount of published literature and consensus guidelines on the diagnosis, prevention, and management of osteoporosis. Also, it took into account local considerations. These recommendations are subject to change pursuant to the following: 1) medical judgment relative to individual patient needs, 2) availability of data on the epidemiology of osteoporosis and osteoporosis-related fractures, and appropriate reference ranges of bone mineral density in Saudi Arabia; 3) availability of new diagnostic strategies and therapies for prevention and treatment of osteoporosis, as well as cost-effectiveness studies, and 4) a definition of the priority of osteoporosis compared to other public health conditions in this country.

3.2% for the 31- to 40-year age group, 5.9% for the 41- to 50-year age group, and 28% for the >50-year age group. The prevalence of osteopenia in the respective age groups was 38%, 38%, and 66%. Severe vitamin D deficiency was present in 52% of the subjects.11 BMD in healthy Saudi females is significantly lower than in their western counterparts. This may be due in part to the prevalent vitamin D deficiency. Vitamin D deficiency may cause osteomalacia and affect the BMD measurement. Correction of the deficiency can result in improvement of BMD. There are also limited data on fracture rates in the region. In a study from Lebanon, Baddourah et al found the lifetime risk for all fractures to be 9.3% in males, and 16.7% in females.7 This rate is higher than other Asian countries, but less than Europe. In Kuwait, Memon et al found hip fracture age-standardized annual rates of 29.5/100 000 in females, and 20/100 000 in males.12 These rates are also higher than what has been reported form other Asian countries. Al-Nuaim et al estimated the incidence of proximal femur fractures for women per 100,000 population to be 4.5 in the 40- to 49-year age group, 14.6 for the 50- to 59-year age group, 79 for the 60- to 69-year age group, and 394 for the >70-year age group. The respective rates for men were 7, 22, 36 and 251.8 The higher incidence of fractures in males compared to females in the age group 40- to 59-year age group is believed to be due to lifestyle factors and involvement in activities that may lead to fractures. It is generally believed that fracture rates in the Saudi population are less than what has been reported from the West. This might be related to genetic factors that may influence bone quality, or cultural and lifestyle differences. Clinical manifestations and complications

Definition of osteoporosis

Osteoporosis is a progressive systemic skeletal disorder characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (NIH Consensus Statement). A fragility fracture is one that occurs as a result of either an injury that is insufficient to fracture normal bone, or as a result of no identifiable trauma (Canadian guidelines). Osteoporosis is a function of bone mass achieved at maturity and subsequent bone loss that is accentuated in the early postmenopausal period, and is influenced by certain risk factors. Osteopenia/osteoporosis and fractures in the region

Local and regional information about osteoporosis and fracture rates is sparse. In a study of 483 postmenopausal Saudi women 52 to 62 years of age, Al Desouki found the rate of osteopenia and osteoporosis to be 34% and 24%, respectively.10 In another study by Al Ghannam et al of 321 healthy Saudi women, the prevalence of osteoporosis was

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Osteoporosis is a silent disease, as bone loss occurs without symptoms. Most of the time there are no warning signs until a fragility fracture occurs. Osteoporosis-related fractures may occur in any bone but are most likely to occur at sites of low bone mass. The most typical sites of osteoporosis related fractures are the vertebrae, distal radius, proximal femur, and ribs. The morbidity of osteoporosis comes mainly from fractures and their potential complications. Vertebral compression fractures are associated with pain, deformity, disability, and increased mortality.13 The most serious consequences, however, are those associated with hip fractures. In one study on elderly subjects who sustained hip fractures, the life expectancy was reduced by 1.8 years or 25% compared to a matched population. There was also a significant increase in morbidity and health costs in those who had hip fracture.14 Evaluation/diagnosis

Optimal evaluation consists of establishing the diagnosis of osteoporosis on the basis of bone mass assessment, es-



Table 1. World Health Organization operational definition of osteoporosis ( WHO Technical Report Series 843, 1994). Definition

Criteria

Normal

BMD within –1 SD of reference mean for young adults

Low bone mass (osteopenia)

BMD within –1.0 and –2.5 SD from reference mean for young adults

Osteoporosis

BMD less than –2.5 SD from reference mean for young adults

Severe

Osteoporosis as defined above with one or more fragility fractures

BMD = bone mineral density, SD = standard deviation.

Table 2. Variables and risk factors of the FRACTURE INDEX and associated score.

Variable/Risk Factor

Score

Age Group (years) Less than 65 65-69 70-74 75-79 80-84 More than 85

0 1 2 3 4 5

Fracture after age 50 years

1

Maternal hip fracture after age 50 years

1

Weight less than 57 kg

1

Current smoker

1

Uses arms to stand from chair

2

Hip BMD (T- score) if done More than –1 –1 to –2 –2 to –2.5 Less than –2.5

0 2 3 4

Adapted from Black D, Steinbuch M, Palermo L, et al, An Assessment Tool for Predicting Risk in Postmenopausal Women, Osteoporosis International 2001; 12:519-528.

tablishing the fracture risk, and determining the need for instituting therapy. Bone strength is related to the density and quality of bone. There is at present no accurate measure for bone quality. BMD is considered a surrogate measure of bone strength. Dual-energy x-ray absorptiometry (DXA) is the preferred technique to measure BMD, and is the technique used at most centers. Quantitative ultrasound is useful for screening for osteoporosis. The hip is the preferred site for BMD measurement due to the high predictive value of hip BMD for fracture risk, particularly in the elderly.15 BMD measurement at the spine predicts spine fracture better than measurements at other sites. However, spine changes may affect BMD measurement. The World Health Organization (WHO) has established an operational definition for osteoporosis based on BMD as measured by DXA, commonly expressed as a T-score (Table 1). A history and a physical examination to evaluate fracture


risks should include assessment for loss of height and change in posture. Laboratory evaluation for secondary causes of osteoporosis should be considered when osteoporosis is diagnosed. Serum calcium, phosphorus, creatinine, vitamin D, a complete blood count and thyroid stimulating hormone (TSH) levels are usually sufficient baseline tests. Further laboratory tests can be done as clinically appropriate, such as parathyroid hormone level, urine free cortisol, liver function tests, or serum immune electrophoresis. Biochemical indices of skeletal turnover could potentially be helpful in the diagnosis and monitoring of therapy. However, as their role has not been fully elucidated, they are not yet recommended in routine clinical management. The decline in bone resorption markers in response to antiresorptive therapy occurs before a significant change in BMD, which may explain the decrease in fracture rates seen early with such therapy, before changes in BMD.16

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Fracture risk factors and fracture index

The FRACTURE Index is a simple clinical tool that was found to be helpful in assessing the risk of hip, vertebral and non-vertebral osteoporotic fractures in elderly postmenopausal women with and without BMD T-scores.9 The FRACTURE Index comprises several variables/risk factors. These variables and the score associated with each variable are summarized in Table 2. Subjects with a score of ≥4 without BMD, or ≥6 with BMD are candidates for screening, prevention or treatment as appropriate. These risk factors could also be useful in assessing the risk of osteoporotic fractures in elderly men.17 This scoring system has however not been evaluated in secondary osteoporosis or steroid-induced osteoporosis.

osteoporosis to determine the need for diagnostic tests and prevention /treatment • Early treatment of secondary causes of osteoporosis (e.g., thyrotoxicosis, smoking, primary hyperparathyroidism, other secondary causes) • Prevention and early treatment of osteoporosis in patients who are receiving high-dose steroid therapy, or other drugs that may contribute to osteoporosis The value of antiresorptive agents for fracture prevention has not been proven for those with no prior fractures, or with BMD greater than -2.5 standard deviations from the reference mean, although such agents might improve or stabilize BMD.5 Therefore, their use should be limited to those with history of fractures or with multiple risk factors for fractures.

Indications for BMD measurement

Some international guidelines for osteoporosis screening recommend BMD testing for all women age 65 years or older, and for postmenopausal women under the age of 65 years (especially, 60-64 years) who have one or more additional high risk factors for osteoporosis.2 However, as the BMD is generally lower in Saudi women compared to their western counterparts, they may develop osteoporosis and fractures at an earlier age. It is also relevant that physical activity, and therefore the risk of falling, may be less in elderly females older than 65 years, according to local cultural habits. Thus, it is reasonable to start screening postmenopausal Saudi women at an earlier age than that recommended for western women. We stress that BMD measurement should only be done if it will influence management decisions. We recommend BMD measurement in the situations described in Table 3.

Management

Important goals in the management of osteoporosis are to prevent fractures, treat pain and discomfort caused by osteoporosis complications, and improve bone density/quality, if possible. Non-pharmacological measures to manage osteoporosis include changing adjustable lifestyle risk factors, preventing falls, maintaining or improving mobility, and increasing weightbearing exercises. Pharmacological measures include treating secondary causes of osteoporosis, and associated disorders, treating pain, discomfort and other associated morbidity, and increasing bone mass. Drugs for osteoporosis primarily reduce bone turnover by inhibiting osteoclast activity. Although they may lead to an early increase in bone mass, the drugs mainly prevent further loss of bone. Agents that primarily increase bone formation (e.g. parathyroid hormone) have only recently become available.

Prevention

Prevention is the most important measure in addressing low BMDs in the youth and in women during reproductive age. Frequent pregnancies and lactation may predispose women in our society to lower BMDs. Thus, proper nutritional and family planning advices are warranted for this group of women. Another important target for prevention is postmenopausal women and those with conditions predisposing to osteoporosis. Initiatives to prevent osteoporosis should include the following measures: • Optimal nutrition in youth to achieve high peak bone mass, including adequate intake of calcium and Vitamin D • Regular weight bearing exercise • Identification and treatment of subjects with Vitamin D deficiency, especially in children, females in the reproductive age group, and the elderly • Avoidance of tobacco smoking and excessive alcohol intake • Assessment of every postmenopausal woman for risk of

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Classes of drugs available for prevention and treatment of osteoporosis (See APPENDIX I and II)

Calcium and Vitamin D supplementation These agents are not sufficient as a sole treatment of osteoporosis, but rather as adjuncts to therapy. They are however essential in any prevention or treatment plans. Calcium and vitamin D decrease bone loss in postmenopausal women, and may reduce the risk of vertebral fractures and possibly non-vertebral fractures, especially in the elderly and in subjects with low calcium and vitamin D. A recent meta-analysis of the effect of calcium and vitamin D showed only an effect of vitamin D in decreasing vertebral fractures.18-20 The recommendation for adequate daily calcium intake, and available products are summarized in Appendix I. For most patients with osteoporosis, diet alone does not provide adequate calcium intake and, therefore, calcium supplementation is necessary. Calcium supplements are better taken with meals. No more than 500 mg of elemental calcium should be taken at a time since excess calcium may not be absorbed as effi-



Table 3. Recommendations for bone mineral density measurement. BMD should be measured in postmenopausal women, particularly those over 60 years, or males over 65 years in the presence of one or more of the following risk factors, or with a FRACTURE index of ≥ 4 without a BMD measurement: - History of early estrogen deficiency Premature menopause (1 year) - Primary or secondary hypogonadism in males - Corticosteroid therapy (>5 mg/day for 3 months or more) - Maternal history of hip fracture - Low body mass index ( 65 years

1000 1500

Table B. Calcium supplements available at King Faisal Specialist Hospital and Research Centre, and on the Saudi National Formulary. Type of Calcium salt

Amount of Calcium salt per tablet (mg)

Elemental Calcium per tablet (mg)

Ca Carbonate [Generic]

Carbonate

650

260

Ca Carbonate +Mg Hydroxide + Na bicarbonate

Carbonate

521

208

Ca Sandoz +Vitamin C Effervescent

Carbonate Lactate-gluconate

327 1000

130 93 + 1000 mg Na bicarbonate + 1000 mg vitamin C

Ca Sandoz Forte Effervescent

Carbonate Lactate-gluconate

300 2940

120 273 + 1000 mg Na bicarbonate

Caltrate 600

Carbonate

1500

600

Caltrate 600 + Vitamin D

Carbonate

1500

600 + 400 IU vitamin D

C-Vimin Ca Effervescent

Carbonate

250

100 + 1000 mg vitamin C

Cebion Ca Effervescent

Carbonate

600

240 + 400 IU vitamin D3 + 1000 mg vitamin C

Kalcipos

Carbonate

500

200

Kalcipos- D

Carbonate

500

200 + 400 IU vitamin D3

Os-Cal 250 mg

Carbonate

625

250

Os-Cal 500 mg

Carbonate

1250

500

Carbonate

420

168

Glycerophosphate

578

225 +1000 mg vitamin C

Amount of Ca per 5 ml (mg)

Elemental Ca per 5 ml (mg)

Name

Titralac Tablets Calcefor effervescent

Calciquid, Neo-Calglucon

Glubionate

1,800

115

Ca gluconate

Gluconate

650

58.5

Glubionate Lactobionate

1,090 723

108

Ca Sandoz syrup


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APPENDIX II Table C. Drugs available at King Faisal Specialist Hospital and Research Centre for prevention or treatment of osteoporosis: Dosage recommendations, and cost relative to the least expensive drug [Expressed as X].

Drugs Hormone Replacement Therapy Conjugated equine estrogen (Premarin®)

Dosage Form

Recommended Dose

Approximate Relative Monthly Cost X

Tablet: 0.3 mg, 0.625 mg, 1.25 mg

0.625 mg OD

+ Medroxyprogesterone acetate (Provera®) for women with intact uterus

Tablet: 2.5 mg, 10 mg, 100 mg

2.5 mg OD

1.5 X

Estradiol valerate (Progynova®)

Tablet: 1 mg, 2 mg

1-2 mg QD

4 X-5 X

Cyclo-Progynova 2 mg (Progyluton®)

11 tablets of 2 mg estradiol valerate [E], and 10 tablets of 2 mg estradiol valerate [E] + 0.5 mg norgestrel [N]

Alendronate (Fosamax)

Tablet: 10 mg Tablet: 70 mg

1 tablet E for 11 days, followed by 1 tablet E+N for 10 days. Leave a tablet free interval of 7 days, then repeat cycle. 10 mg OD 70 mg once weekly

17 X 19 X

Calcitonin (Calcimar®; Miacalcic®)

Intranasal spray 100 IU/ metered dose Tablet: 60 mg

200 IU OD

83 X

60 mg OD

20 X

Raloxifene (Evista®)

251

1.5 X



Table D. Drugs available at King Faisal Specialist Hospital and Research Centre for prevention and treatment of osteoporosis. Drugs

Adverse Reactions

Drug interactions

Contra-indications

Precautions/Comments

Hormone Replacement Therapy

Serious: Venous thromboembolism, stroke, coronary artery disease, breast carcinoma, hepatic adenoma, gallbladder disease, cholestatic jaundice, pancreatitis, and hypertension. Increased risk of endometrial cancer, and possibly ovarian cancer in women taking unopposed estrogen Common: menstrual irregularities, breast tenderness, nausea, bloating, abdominal cramps, vomiting, headache, dizziness, depression, peripheral edema, weight changes, rash, intolerance to contact lenses, libido changes, increased HDL, decreased LDL and total cholesterol, increased triglycerides

Barbiturates, steroids, insulin, hypoglycemic agents, phenytoin, rifampicin, ursodiol

Hypersensitivity to drug/ class/ component; unexplained vaginal bleeding; thrombophlebitis, thromboembolic disorders or history of thromboembolic disease; coronary artery disease; liver disease; known or suspected pregnancy; carcinoma of the breast; and estrogen -dependent tumors

Use with caution in patients with asthma, diabetes, epilepsy, migraine headache, or heart, kidney, liver, or gallbladder disease. Daily combination of 0.625 mg of conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate in healthy postmenopausal women (average follow-up of 5.2 years) was associated with the following absolute excess risks per 10,000 person years: 7 heart attacks, 8 strokes, 18 blood clots, and 8 breast cancers (39).

Alendronate (Fosamax)

Serious: Esophagitis, gastritis Common: abdominal pain, myalgias, arthralgia, back pain, nausea, dyspepsia, constipation, diarrhea, flatulence, headache, acid reflux, vomiting, dysphagia, abdominal distension, chest pain, peripheral edema, flulike symptoms, esophageal ulcer

Antacids, calcium salts, and multivitamins with minerals may decrease absorption of bisphosphonates

Hypersensitivity to drug/ class/ component; hypocalcemia; abnormalities of the esophagus which delay esophageal emptying (stricture, achalasia); inability to stand or sit upright for at least 30 minutes; GI bleeding; severe renal dysfunction

Use with caution for patients with moderate renal insufficiency, ulcers, heartburn, hypoparathyroidism, pregnancy, and breast feeding. Correct hypocalcemia and disturbances of mineral metabolism before initiating alendronate

Calcitonin (Calcimar, Miacalcic)

Nasal irritation, rhinitis, back pain, arthralgias, epistaxis, headache, sinusitis, dizziness, nausea, vomiting, flushing, rash

Plicamycin may enhance hypocalcemic effect of calcitonin.

Hypersensitivity to the drug/class/ components [salmon protein or gelatine diluents]

A skin test should be performed prior to initiating therapy of calcitonin salmon; Use with caution in pregnant women

Raloxifene (Evista)

Serious: Deep vein thrombosis, pulmonary embolism, retinal vein thrombosis. Common: Hot flashes, flu-like symptoms, arthralgias, sinusitis, nausea, weight gain, pharyngitis, depression, cough, leg cramps, rash, insomnia, dyspepsia

Cholestyramine reduces the absorption of raloxifene. Raloxifene should not be used with high protein bound drugs.

Hypersensitivity to drug, class/ component; pregnancy or planned pregnancy; deep vein thrombosis, or history of deep vein thrombosis

Patients with cardiovascular disease, history of cervical/uterine carcinoma, or renal/ hepatic insufficiency; not to be used concurrently with estrogens


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ORIGINAL ARTICLE

EXPERIENCE WITH A MOBILE ANGIOGRAPH WITHOUT ON-SITE SURGICAL BACK-UP

Three years of experience with a mobile angiograph in a center without on-site surgical back-up Ramazan Akdemir, MD; Hakan Ozhan, MD; Mehmet Yazici, MD; Huseyin Gunduz, MD; Enver Erbilen, MD; Sinan Albayrak, MD; Cihangir Uyan, MD

Background: The safety of percutaneous coronary interventions (PCI) performed in centers without surgical back-up is controversial, but data from several western countries indicates that this approach can be extended to a larger number of hospitals. We assessed the safety and efficacy of performing angiography and PCI with a mobile Carm angiograph in a center without on-site surgical back-up, and compared our data with that reported in the literature. Methods: We retrospectively analyzed 1485 coronary angiograms and 172 PCI procedures performed in our center from January 2001 to May 2003 using a mobile angiograph. Half of the patients that have undergone PCI had refractory unstable angina and one-third had acute myocardial infarction (AMI). The safety of PCI was assessed by the analysis of in-hospital complications (death, urgent need for repeated revascularization, AMI with or without ST elevation and stroke).The PCI procedures were considered effective when the post-PCI residual stenosis did not exceed 50% with distal Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. Results: In patients who underwent diagnostic coronary angiography there were no deaths, anaphylatic shock, acute renal failure or major ischemic complications. In patients who underwent PCI, the mortality rate was 1.1% (2 deaths), two patients (1.1%) developed acute MI with ST segment elevation, one patient (0.5%) underwent repeated PCI and three patients (1.7%) were referred for urgent by-pass surgery. Conclusions: Diagnostic and PCI procedures can be safely performed using a mobile angiograph. The efficacy and safety requirements of PCI, performed in a center without an on-site surgical back-up facility using a mobile angiograph were similar to other data reported in the literature.

From the Department of Cardiology Abantizzet Baysal University Duzce Faculty of Medicine, Konuralp Duzce Turkey Correspondence to : Dr. Hakan Ozhan Abantizzet Baysal Universitesi Duzce Tip Fakultesi 81000 Konuralp Duzce Turkey E-mail: [email protected] Accepted for publication: May 2004 Ann Saudi Med 2004;24(4):253-258

Key words: Percutaneous coronary interventions, mobile angiography, coronary artery disease, angioplasty, Turkey

C

oronary angiography is the gold standard in diagnosing coronary artery disease (CAD), but it is expensive. Technological innovations now allow mobile angiographs to compete with conventional stationary machines. Percutaneous coronary interventions (PCI) are an important part of diagnosis in cardiovascular disorders. The need for cheap but powerful angiographs will increase in the future. A topic of debate is the safety issue of PCI performed in centers without surgical back-up. Although PCI is recommended for the management of acute myocardial infarction (AMI) and refractory unstable angina, less than 10% of European hospitals are equipped with PCI facilities. Some are equipped with mobile fluoroscopy machines and even less have on-site cardiac surgery back-up.1,2 A meta-analysis of ten multicenter randomized trials indicated that primary angioplasty in AMI lowers the

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rates of death, stroke, recurrent ischemia and re-infarction compared with fibrinolytic therapy.3 In addition, for low risk patients with AMI, the mortality of primary angioplasty can be very low (50%), contraindications to anti-platelet therapy, or >3 stents needed for one target site. In most cases we used Ephesus stents (Nemed Corporation, Turkey), a stainless-steel, laser-cut, tubular, slotted-tube multi-cellular device mounted on customized, non-compliant, polyethylene terephthalate, with a non-tapered short balloon overhang (0.5 mm). In the unexpended state, the crossing profile is 0.048”. Clopidogrel 300 mg was administered orally before the intervention. Procedures were performed using standard angioplasty technique with an 8 French (Fr) guiding catheter via the femoral artery. A bolus of 100 IU/kg of heparin was administered intra-arterially after insertion of the vascular access sheath. Target lesions were initially treated with appropriate balloon dilatation. Intracoronary stenting was carried out after a sub-optimal result following conventional balloon angioplasty. The stent sizes were determined based on a stent-to-artery ratio of 1.1: 1 to 1.2:1. The stents were deployed at 8-14 atmospheres and high-pressure balloon inflation to 14 atmospheres was then applied with a non-compliant short balloon to avoid distal dissection. Post-procedure medication protocol and follow-up. After successful stent implantation, heparin was not routinely administered unless there was a clinical indication, such as a large residual dissection. The sheaths were removed the same day. After sheath removal, experienced technicians performed manual compression of the puncture site, and then applied a pressure bandage for 6 hours. Ambulation was allowed 6 hours after sheath removal. Clopidogrel 75 mg once daily was continued for 4 weeks and aspirin 100-300 mg once daily was continued indefinitely. Electrocardiograms (ECG) were recorded immediately after the procedure, then daily before discharge. If the patient had recurrent chest pain post-procedure, a creatine kinase-myocardial band (CK-MB) level was measured and an additional ECG was recorded. The majority of patients were discharged 2 days after the procedure. Follow-up coronary angiography was performed at 6 months, or earlier if clinically indicated. Laboratory and operators. The fluoroscopy machine was a Siemens C-800 Powermobil (Erlangen, Germany) with an

Table 1. Number of diagnostic and therapeutic interventions performed in the study population. Year

Coronary angiography

Percutaneous coronary intervention

Pacers implanted

Intracardiac defibrillators

2001

350

30

5

–

2002

740

69

9

1

2003

395

82

1

–

Total

1485

172

15

1


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Table 2. Clinical and demographic characteristics of percutaneous coronary intervention patients. n (%) Male/female

134/38 (77.9/22.1)

Hypertension

35 (20.3)

Diabetes mellitus

56 (32.5)

Hyperlipidemia

42 (24.4)

Stable angina

36 (20.9)

Unstable angina

80 (46.5)

Acute MI

56 (32.5)

Cardiogenic shock

11 (6)

Table 3. Angiographic characteristics of the PCI patients and overall procedural data. Procedure

n (%)

Total number of PCI

172 (100)

Total number of dilated lesions

225 (100)

Single vessel disease

119 (69.1)

Two vessel disease PTCA alone/stent implanted IIb/IIIa receptor blocker usage

53 (30.8) 24/201 (10.6/89.3) 35 (20.3)

X-ray generator of maximum 20 kW output. The machine has a digital cine mode with a pulse rate up to 25 frame/sec at 60 Hz. The digital processor can eliminate motion-dependent noise. The C-arm can rotate 182o and angulate ±190o. An ambulance was available for urgent transport. A tertiary center (Kosuyolu Heart Center, approximately 200 kilometers away) with facilities for cardiovascular surgery for 24 hours a day was available for any urgent cases. Two experienced operators performed diagnostic coronary angiography and PCI procedures. Both had performed more than 2000 coronary angiograms and 500 PCI procedures from January 1998 until December 2000 as the primary operator before working in the department where the study was performed. The nursing and technical catheterization laboratory staffs were experienced in handling acutely ill patients and comfortable with interventional equipment. They participated in PCI procedures on a 24hour, 365-day call schedule. The catheterization laboratory was well equipped with resuscitative equipment and well stocked with a broad array of interventional equipment. The cardiac care unit nurses were trained for hemodynamic monitoring.There was an ongoing program for outcome analysis and formalized periodic case review. Definitions and angiographic analysis. Quantitative coronary angiographic analysis was performed using the quantitative coronary analysis system (AETMED S.P.a., Italy). Angiographic measurements were obtained during

255

end-diastole using the image that showed the greatest narrowing, without overlap and with the least degree of foreshortening. Intra-coronary nitroglycerin was administered at baseline and final angiography. Measurements of the reference vessel diameter, minimal lumen diameter (MLD) and percent diameter stenosis were determined by an average of two orthogonal views. The index reference diameter was the average of the proximal and distal reference vessel diameters. Lesion length was measured on the baseline angiography using the “shoulder-to-shoulder” definition. The morphology of the coronary lesions was classified as A, B1, B2 and C according to Ellis’ modification of the classification proposed by the American College of Cardiology and the American Heart Association Task Force.6 Changes in MLD were expressed as acute gain (post-procedural MLD minus pre-procedural MLD), late loss (post-procedural MLD minus 6-month follow-up MLD), and loss index (late loss/acute gain). Angiographic restenosis was defined as re-narrowing of the target lesion >50%. Q-wave myocardial infarction was defined as the development of new abnormal Q-waves not present at baseline in association with CK-MB enzyme elevation of three times the upper normal limit and non-q wave myocardial infarction was defined as CK and CK-MB elevation of three times the upper normal limit. Angiographic success was defined as (50% reduction in the diameter of the stenosis. Procedural success was defined as angiographic success without the occurrence of any major ischemic complications during hospitalization. A sub-optimal result was defined as a 30-50% residual stenosis after coronary angioplasty with a TIMI 3 flow. Restenosis was defined as the occurrence of >50% stenosis at the site of angioplasty, or clinical evidence of ischemia in the territory of the dilated vessel. Complications. Vascular complications were defined as pseudoaneurysm formation, arteriovenous fistula, thrombotic occlusion requiring intervention and major bleeding from the puncture site necessitating blood transfusion. Major ischemic complications were defined as the occurrence of myocardial infarction, death or the need for emergency coronary artery bypass grafting. Data collection and statistics. Demographic, clinical and technical data were gathered retrospectively. Follow-up coronary angiography was performed 6 months after the procedure. Statistical analysis was performed with SPSS 10.0 for Windows. Continuous variables are expressed as mean±SD. Results

There were no deaths, anaphylactic shock, acute renal failure or major ischemic complications in the diagnostic coronary angiography group. Two patients had femoral artery pseudoaneurysms and were treated with surgery, and two patients had strokes. One, a 68-year-old male, had LMCA disease and a right occipital lobe infarction of the



Table 4. Pre- and post-procedural angiographic characteristics (n=110). Characteristics Reference lumen diameter (mm) Minimum lumen diameter (mm) Percent diameter stenosis (%)

Pre-procedure

Post-procedure

2.74 ± 0.42 1.02 ± 0.46

2.85 ± 0.28 2.42 ± 0.33

82 ± 16

16 ± 4

12.7 ± 4.7

–

Binary restenosis (>50%)

–

–

Acute gain (mm)

–

1.43 ± 0.48

Late loss (mm)

–

–

Loss index

–

–

Lesion length (mm)

Table 5. Outcome for all PCI procedures. In-hospital outcome (n=172)(%) Total mortality

2 (1.1)

Death during PCI

1 (0.5)

Death during hospital follow-up

1 (0.5)

Acute MI with ST elevation

2 (1.0)

Acute MI without ST elevation

0

Need for repeat PCI

2 (1.1)

Need for urgent surgery

3 (1.7)

Stroke

0

brain. The other, a 72-year-old female had hemiplegia on the left side on the day after coronary angiography had been performed. Computerized tomography revealed a right parietal lobe infarction of the brain. Baseline clinical and angiographic data for the patients who received PCIs are summarized in Tables 2, 3 and 4. The mean age of the 172 PCI patients was 58.1±11 years (mean±SD). There were a high proportion of patients with hypertension (40%) and diabetes mellitus (32%). Approximately half of the patients had refractory unstable angina and nearly one-third of the patients had received primary PTCA. Type B and C lesions were present in 36.9% of patients according to the ACC/AHA classification. The mean reference lumen diameter was 2.74±0.42 mm and 62% of the lesions were under 3 mm in diameter. In 7 cases in 172 patients the stent could not be deployed. The device success rate was 96%. The mean pressure used for stent deployment was 11.4±2.6 atm. The acute gain was 1.43±0.48 mm. Direct stenting was feasible in 52 patients with type A lesions and predilatation of lesions was performed in the majority of patients using undersized balloons with average pressures for 60 seconds. Events such as stent lost, stent dislocation or balloon burst before optimal deployment did not occur. No acute or subacute stent thrombosis occurred. Platelet glycoprotein IIb/IIIa receptor blockers were used in 35 (20%) patients (all tirofiban) in whom PTCA was


performed in the acute phase of MI. In none of the elective procedures was the use of these agents necessary. Early clinical outcomes of the patients are shown in Table 5. In-hospital and procedural total mortality was 1.1% (2 patients). Both patients had acute MI complicated with cardiogenic shock on admission. One died during PCI from refractory ventricular fibrillation and the other died during hospital follow-up due to advanced low cardiac output upon intraaortic balloon pumping. Three patients had been sent for urgent cardiac surgery because of cardiogenic shock untreatable by PCI alone. One had acute mitral regurgitation; the second had ventricular septal rupture and the third had acute papillary muscle rupture associated with acute MI. Discussion

Although the number of invasive procedures performed in Turkey in patients with ischemic heart disease constantly increases, it is still lower than the expected number because of limited access to catheterization laboratories. A possible solution to this problem-use of mobile angiographs in hospitals without on-site cardiac surgery-has some drawbacks. ACC/AHA guidelines do not recommend elective PCI and primary PCI without on-site cardiac surgery except when there is a proven plan for rapid access to a cardiac surgery room within 1 hour. However, the guidelines stress that that

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complication rates will be subject to future revision as newer data emerge.7 The rationale behind PCI without on-site surgery is the decrease in need for emergency coronary artery bypass, which ranges between 0.4% and 2%,8 with the advent of intracoronary stenting. Not surprisingly, emergency coronary artery bypass for a patient with an occluded or dissected coronary artery is associated with a higher mortality than elective surgery.9 Emergency procedures are also associated with high rates of per operative infarction and less frequent use of arterial conduits. Complex CAD intervention, hemodynamic instability, and prolonged time to reperfusion are contributing factors to the increased risk of emergency bypass surgery. These data encouraged the authors to perform PCI in hospitals without on-site surgery. Many studies report successful angioplasty series without on-site surgical backup and with little need for off-site surgery in failed angioplasty. Nevertheless, the appropriateness of elective angioplasty in centers without on-site surgical coverage is a concern.10 PCI were performed in AMI patients by Wharton et al. and in refractory unstable angina by Michalis et al., in hospitals without on-site surgery with excellent results.11,12 Hayat et al. performed PCI in 117 consecutive patients without applying any exclusion criteria. Patients had stable angina, unstable angina and silent ischemia. Angiographic success was 91% with major complications in only four patients (1 death, 2 AMI and 1 tamponade) with no need for emergency surgery.13 The ACC/AHA guidelines recommend timely management of ischemic complications, adequate specialized post-interventional care, logistics for managing cardiac surgical or vascular complications and operator/laboratory volumes.7 Interventional cardiology procedures are associated with complications that in general are inversely related to operator and institutional volume.14 All of the procedures in our study were performed with a mobile angiograph. While the usefulness of this type of angiograph for coronary angiography has been well documented, the safety and efficacy of PTCA performed with the use of mobile angiograph has been a matter of debate in the interventional cardiologist community, mainly because of certain drawbacks with this type of equipment. The main disadvantages include a less effective cooling system, References

1. Braunwald E, Jones RH, Mark DB, et al. Diagnosing and managing unstable angina. Agency for Health Care Policy and Research. Circulation. 1994; 90: 613-622. 2. Lange RA, Hillis LD. Should trombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction. N Eng J Med. 1996; 335: 13111312. 3. Weaver WD, Simes RJ, Betriu A, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a

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which leads to the x-ray tube overheating during the longer duration of fluoroscopy, particularly during projections with the voltage close to the maximal values. There is also an increased risk of an automatic temporary switch-off due to overheating with the machine turning back on after as long as several minutes, and the inferior quality of the images in some projections and in obese patients. The advantages include low cost, feasibility of installation, ease of use, a modern digital recording system on CD ROM in the DICOM system and the mobility of the apparatus. In recent years, portable fluoroscopic imaging systems have been developed to reduce costs and bring coronary angiography services closer to patients. Vergara demonstrated the reliability of the new generation mobile systems with respect to the quality of coronary angiograms and the routine use in a multipurpose cardiac catheterization laboratory.15 Carosio et al compared a portable system with a stationary system, and found complete concordance between the systems for lesion location, stenosis quantification, morphologic characterization, TIMI flow and collateral demonstration, concluding that a portable imaging system can produce high-quality images.16 Aliabadi et al. found similar results.17 Reczuch et al. reported a mortality rate of 0.4% and a major adverse cardiac event rate of 0.9% in 687 PCI patients, including AMI patients. There was no need for urgent cardiac surgery. The major cardiac event rate in our study was 4.5% and the in-hospital mortality rate was 1.2% after PCI. Urgent cardiac surgery was need in 1.7% of patients.18 These data are compatible with a recent study published by Anderson et al. which was based on PCI data collected and analyzed by the American College of Cardiology-National Cardiovascular Data Registry from January 1, 1998, through September 30, 2000 from 100 292 PCI procedures. Anderson et al reported 77% stent utility and an overall mortality rate of 1.4%.19 We think that because of achievements in stent technology and newly available drugs, diagnostic coronary angiography can be safely performed with mobile angiographs in all patients and electively to selected patients without the need for surgical standby. However, large, prospective, randomized trials are needed to increase the evidence level for this approach.

quantitave review. JAMA. 1997; 278: 2093-2098. 4. Grines CL, Marsalese DL, Brodie B, et al. Safety and cost-effectiveness of early discharge after primary angioplasty in low risk patients with acute myocardial infarction. PAMI-II Investigators. Primary Angioplasty in Myocardial Infarction. J Am Coll Cardiol. 1998; 31: 967-972. 5. The TIMI Study Group. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-

Q-wave myocardial infarction: results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia. Circulation. 1994; 89: 1545-1556. 6. Ryan TJ, Faxon DP, Gunnar RP. The ACC/AHA Task Force. Guidelines for percutaneous transluminal coronary angioplasty. J Am Coll Cardiol. 1988; 12: 529-545. 7. Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines)-executive sum-



mary: a report of the American College of Cardiology/ American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions. Circulation. 2001; 103: 3019-3041. 8. Stauffer JC, Eeckhout E, Vogt P, Kappenberger L, Goy JJ. Stand-by versus stent-by during percutaneous transluminal coronary angioplasty. Am Heart J. 1995;130:21-26. 9. Berger PB, Stensrud PE, Daly RC, et al. Time to reperfusion and other procedural characteristics of emergency coronary artery bypass surgery after unsuccessful coronary angioplasty. Am J Cardiol. 1995; 76: 565-569. 10. Kent KM. Interventional cardiology: 1990s. Am J Cardiol. 1992;70:1607-1608. 11. Wharton TP Jr, McNamara NS, Fedele FA, Jacobs MI, Gladstone AR, Funk EJ. Primary angioplasty for the

treatment of acute myocardial infarction: experience at two community hospitals without cardiac surgery. JACC. 1999; 33: 1257-1265. 12. Michalis LK, Stroumbis CS, Pappas K, et al.Treatment of refractory unstable angina in geographically isolated areas without cardiac surgery. Invasive versus conservative strategy (TRUCS study). Eur Heart J. 2000; 21: 1954-1959. 13. Hayat NJ, Varghese K, Salman H, Elghoul S, Abraham MT. Angioplasty in the stent era: results of a consecutive series of patients undergoing coronary angioplasty without surgical backup. Int J Card. 1998; 64: 241-246. 14. Jollis JG, Peterson ED, Nelson CL, et al. Relationship between physician and hospital coronary angioplasty volume and outcome in elderly patients. Circulation. 1997;95:2485-2491. 15. Vergara G. Hemodynamics studies with the new generation portable systems: cost-benefit analysis. Ital Heart J. 2001; 2 :22-25.


16. Carosio G, Taverna G, Ballestrero G, Reale M, Molendi V. Portable fluoroscopic X-ray systems and traditional fixed angiographic systems: a comparison in the detection of coronary stenosis. G Ital Cardiol. 1998; 28: 979-983. 17. Aliabadi D, Pica MC, McCullough PA, et al. Rapid bedside coronary angiography with a portable fluoroscopic imaging system. Cathet Cardiovasc Diagn. 1997; 41: 449-455. 18. Reczuch K, Rubin W, Szajn G, et al. Safety and efficacy of percutaneous coronary revascularisation performed with the use of mobile angiograph. Kardiol Pol. 2002; 56: 307-312. 19. Anderson HV, Shaw RE, Brindis RG, et al. A contemporary overview of percutaneous coronary interventions. The American College of CardiologyNational Cardiovascular Data Registry (ACC-NCDR). J Am Coll Cardiol. 2002; 39: 1096-1103.

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ORIGINAL ARTICLE

MAGNESIUM AND CARDIAC INJURY

Magnesium decreases cardiac injury in patients undergoing coronary artery bypass surgery Adem Grbolar Resatoglu,MD; Orhan Saim Demirturk,MD; Nuran Yener,PhD; Ali Yener,MD

Background: The calcium-channel blocking effect of magnesium might have protective effects in patients undergoing cardiopulmonary bypass surgery. We assessed the effects of magnesium on hearts undergoing coronary artery bypass surgery with intermittent warm blood hyperkalemic cardioplegia in the antegrade fashion. Patients and Methods: Twenty patients undergoing coronary bypass surgery were randomly divided into two groups, a control group who received intermittent antegrade warm blood hyperkalemic cardioplegia for myocardial protection, and a study group who received the same solution with the addition of magnesium to the cardioplegia. Extracellular substrates (creatinine phosphokinase, creatinine phosphokinase-MB group, lactate dehydrogenase, c-reactive protein, and cardiac troponin I were measured preoperatively and postoperatively. Results: There were significant differences in the post-operative concentrations of creatinine phosphokinase, creatinine phosphokinase-MB group, c-reactive protein, and lactate dehydrogenase after cardiopulmonary bypass (P