NEWS & VIEWS

Progress in Interventional Cardiology

This issue of News & Views highlights progress reported at the 14th Congress of the European Society of Cardiology (Barcelona, Spain, August 30-September 3, 1992). Additionally, recent in- sights from the literature will be reviewed.

At the European Society of Cardiology particu- lar noteworthy presentations were made on acute myocardial infarction (MI), restenosis after elec- tive percutaneous transluminal coronary angio- plasty (PTCA), and the use of new devices in evaluation and treatment of coronary artery disease.

Acute Myocardial Infarction

The latest results of several clinical trials were reported at the European Congress. The Gram- pian Region Early Anistreplase Trial (GREAT) study evaluated domiciliary thrombolysis by gen- eral practitioners in the Grampian region (Aber- deen, Scotland) using anistreplase (APSAC) in patients with acute MI. APSAC was administered at home within 1 hour and 45 minutes and at the hospital within 4 hours of acute MI. In 3 months, 8% of home-treated patients had died and Q wave MI evolved in 50%. By contrast, 16% of hospital- treated patients died and 70% developed a Q wave MI in the same interval. Left ventricular function was improved in patients treated within 2 hours, as compared to those who received treat- ment later.

This study confirms the findings of the Myocar- dial Infarction Triage and Intervention (MITI) Trial and the European Myocardial Infarction Project (EMIP) reported at the recent American College of Cardiology meetings (41st Annual Sci- entific Session, Dallas, Texas).'-' These trials evaluated the use of prehospital administration of thrombolytic agents in patients with acute MI. In MITI and EMIP, early administration of lytic

Address for reprints: J . David Talley, M.D., University of Louisville, Department of Medicine, Ambulatory Care Build- ing, Louisville, KY 40292. Fax: (502) 588-7147.

therapy improved indices of cardiac performance including infarct size, left ventricular function, and survival. These studies support the concept of early diagnosis and thrombolysis, regardless of location of administration, for improvement in long-term outcome.

The results of the Late Assessment of Throm- bolytic Efficacy (LATE) trial were reported in Barcelona. This trial enrolled patients who pre- sented more than 6 hours after acute MI and who had either clinical or electrocardiographic evi- dence of ongoing myocardial injury. Mortality at 35 days and 1 year were primary outcomes for analysis. There were 5,709 patients randomized to receive either placebo or plasminogen activa- tor (rt-PA; 100 mg/3 hours). All patients received aspirin, and adjunctive intravenous heparin was recommended. The outcome and complications of the study are summarized in Tables 1 and 2. At 35 days, a fatal outcome occurred in 8.8% of the rt-PA group and 10.3% in the placebo cohort (P = NS). When the 35-day mortality was ana- lyzed by time to treatment, patients who were treated between 6-12 hours after the onset of symptoms were more likely to survive. In the rt- PA group, the mortality was 8.7% and in the pla- cebo group, 11.9%, a 27% risk reduction (P = 0.033). There was a price to pay, however, for this benefit, stroke occurred in 2.25% of the rt- PA group and only 1.1% in those randomized to placebo.

The implications of the LATE study, while sig- nificant, require further analysis. It is estimated that approximately 30% of patients with acute MI present to the hospital after 6 hours of symptom onset (nearly 35,000 patients in the United States, alone). This group would appear to benefit from treatment with thrombolytic agents, but the risk of stroke is frightening. Subgroup analysis, with all its limitations, will be important in LATE. What were the clinical and electrocardiographic predictors of improved survival and what vari- ables were associated with the development of a stroke? Hopefully, this data will be part of the published manuscript.

Vol. 5, No. 4, 1992 Journal of Interventional Cardiology 337

TALLEY

Table 1. 35 Day Mortality in the LATE Trial

Time to

(hours) rt-PA Placebo Reduction P Value

6-12 8.7% 11.9% 27% 0.033 12-24 8.7% 9.2% 5% NS 6-24 8.8% 10.3% 14.6% N S

LATE = Late Assessment of Thrombolytic Eficacy: rt-PA = recombinant tissue plasminogen activator.

Treatment Risk

Restenosis After Elective Percutaneous Transluminal Coronary Angioplasty

The cellular mechanism( s) of restenosis after PTCA was discussed at the European Congress. Smooth muscle cells, cultured from primary and restenotic coronary lesions obtained by direc- tional coronary atherectomy (DCA), demon- strated diminished proliferation as compared to cells from a control artery. However, an in- creased extracellular matrix protein synthesis was found. Restenosis after DCA cannot be pre- dicted by clinical, procedural, or angiographic profiles; however, an increased cellular content and an echolucent appearance of the plaque be- fore resection identified by intracoronary ultra- sound predicted a higher restenosis

Pharmacological and mechanical methods to prevent restenosis were extensively discussed. Trapidil acts on arachidonic acid to inhibit plate- let growth factor and also produces vasodilata- tion and inhibits thromboxane. It was shown to decrease restenosis compared to aspirin in a rab- bit model .8 Dexamethasone significantly reduced restenosis by decreasing the number of proliferat- ing smooth muscle cells at an early stage after intervention. Although the influence of inflation duration on the outcome after PTCA is still con-

Table 2. 35 Day Stroke Incidence in the LATE Trial

Type of Stroke rl-PA Placebo

Fatal 0.95% 0.42% Non-fatal 1.3% 0.68% Total 2.25% 1 . 1 %

LATE = Late Assessment of Thrombolytic Efficacy; rt-PA = recombinant tissue plasminogen activator.

troversial, it was reported that progressive and prolonged balloon inflation yields optimal angio- graphic results with less residual stenosis (per- haps due to reduced elastic recoil) than standard balloon inflation protocols. It was also noted that the achievement of a larger lumen as with stent implantation or DCA does not necessarily predict an improved long-term outcome. These interven- tions are associated with a large late loss of lumen caliber. For an extensive discussion of this para- doxical association, please see a prior News & Views.'

New Devices in the Treatment of Coronary Artery Disease

Intracoronary Stents. The 5-year follow-up of patients in whom a Wallstent (Medivent, Plym- outh, MN, USA) was implanted was reported. Despite early thrombus formation and smooth muscle cell proliferation at 42 days after implanta- tion, long-term patency is favorable. If a patient is free of complications and has a patent stent 6 months after the procedure, late restenosis is rare even 5 years after implantation.'**"

Acute thrombosis continues to plague stenting. The 7% rate of acute thrombosis is even greater when the stent is placed as a "bail out proce- dure," after multiple stent implantations, or when the final stent diameter is 5 3.25 mm. Thrombus formation may be treated with recom- binant hirudin and aspirin. The high rate of com- plications observed with conventional stents has focused research on other less thrombogenic ma- terials. A mesh stent constructed of polyethylene terephthalate showed a favorable patency profile without need for antithrombotic therapy. Neoin- timal proliferation in an animal model appeared to be

Laser Percutaneous Transluminal Coronary An- gioplasty. Insufficient ablation energy at the cath- eter tip, perhaps improved by increasing optical fiber density, was noted by Mehta and the Euro- pean Study G r o ~ p , ' ~ - ' ~ for excimer laser coro- nary angioplasty (ELCA). The European study group reported quantitative angiographic data of 438 lesions subject to ELCA. There was a mean 20% decrease in lesion severity after ELCA with a mean residual stenosis of 60%. Thus, in the ma-

338 Journal of lnterventional Cardiology Vol. 5, No. 4, 1992

NEWS & VIEWS

Vol. 5 , No. 4, 1992 Journal of Interventional Cardiology 339

jority of cases, additional balloon dilatation was required.

Several presentations focused on acute compli- cations associated with ELCA including: tissue damage inflicted to the surrounding arterial wall, vessel wall dissection and perforation. The latter was noted more frequently in diabetic patients or in those with ELCA performed on small vessels or bifurcation It appears that ELCA can be performed with rates of success and com- plications similar to that of balloon PTCA. ELCA is suitable for ostial, long, and calcified lesions, as well as for total occlusions.

Intracoronary Doppler Guidewire. Currently, a 0.018-in Doppler-tipped guidewire is available to determine intracoronary blood velocity. This technique showed that PTCA does not normalize flow reserve although the baseline and the hyper- emic peak velocity increase after successful PTCA.” This technology potentially provides an “online” assessment of the success of the proce- dure and points to the relationship of anatomical and physiological determinants of successful res- toration of coronary artery patency.

Lessons from the Literature

The 18-year follow-up from the Veterans Af- fairs (VA) Cooperative Study of Coronary Artery Bypass Surgery was recently reported in the July issue of Circulation.” This report describes the 18-year experience of 686 patients randomized to medical management versus coronary artery by- pass graft (CABG) surgery between 1972-1974. In virtually all patients without left main coronary artery disease, the improved symptomatic status and survival benefit noted earlier in the surgical subgroup disappeared. One intriguing finding was that CABG surgery did not improve survival by preventing acute MI but did improve survival after the occurrence of acute MI. The authors suggested that this surgical benefit was gained from patent grafts functioning as collaterals. On the other hand, when bypass grafts closed symp- tomatic improvement, freedom from myocardial infarction, and survival benefit declined dramati- cally.

Methods of infection control are the subject of

the two recent reviews. Transparent polyure- thane film catheter dressing was the subject of a recent meta-analysis of nosocomial blood infec- tions in hospitalized patients who had central or peripheral venous cannula. It was concluded that the risk for catheter tip infections for patients with either central or peripheral venous catheters was greater with the use of transparent film as compared to conventional gauze dressing^.'^ While this study addressed only venous cathe- ters, the findings have implications for the use of transparent film covering large bore arterial catheters such as those used with PTCA or in- traaortic balloon pump insertion. Finally, a pro- spective, randomized trial of routine or scheduled replacement of central venous and pulmonary-ar- tery catheters in 160 patients showed that routine replacement did not prevent infection. Replace- ment over a guidewire increased the risk of bac- teremia while replacement at a new site increased the likelihood of a mechanical c~mplication.’~

The next News & Views will highlight the re- sults from the 65th Scientific Sessions of the American Heart Association (New Orleans, Lou- isiana, November 16-19, 1992).

Herbert J . Geschwind, M.D. Professor

HGpital Henri Mondor Creteil, France

and J . David Talley, M.D.

Interventional Cardiology University of Louisville

Louisville, Kentucky

References

1. Hallstom A. Myocardial infarction triage and interven- tion (MITI) trial of pre-hospital initiated thrombolysis- design, endpoints, and baseline characteristic. Pre- sented at the Clinical Trials Symposium of the American College of Cardiology, 41st Scientific Session. Dallas, TX, April 14, 1992. Weaver WD. Myocardial infarction triage and interven- tion (MITI) trial of pre-hospital initiated thrombolysis- results. Presented at the Clinical Trials Symposium of the American College of Cardiology, 41st Annual Scien- tific Session. Dallas, TX, April 14, 1992.

3. Leizorovicz A. Design and study population [of EMIP]. Presented at the European Myocardial Infarction Project (EMIP) Symposium of the American College of

2.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

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Cardiology, 41st Annual Scierrtific Session. Dallas. TX. April IS, 1992. Julian D. Safety aspects and delays for in-hospital thrombolysis: The EMIP findings. Presented at the Eu- ropean Myocardial Infarction Project (EMIP) Sympo- sium of the American College of Cardiology, 41st An- nual Scientific Sessions. Dallas, TX, April 14, 1992. Boissel J-P. EMIP: Short term mortality and non-fatal outcomes. Presented at the European Myocardial In- farction Project (EMIP) Symposium of the American College of Cardiology, 41 st Annual Scientific Session. Dallas, TX, April IS, 1992. MacLeod DC, de Jong M, Strauss BH, et al. Attenuated proliferation but enhanced extracellular matrix protein synthesis of coronary smooth muscle cells cultured after directional atherectomy in man. (abstract) Eur Heart J 1992; 13:310. Zeiher AM, Hohnloser S. Fassbender S, et al. Intracoro- nary ultrasound morphology following interventional therapy in coronary artery disease. Eur Heart J 1992: 13:308. Maresta A, Balducelli M, Cantini L, et al. Trapidil (platelet derived growth factor antagonist) in the preven- tion of restenosis after PTCA: A double blind random- ized multicenter study. (abstract) Eur Heart J 1992: 13: 82. Talley JD. News & Views: Progress in interventional cardiology. J Interven Cardiol 1992; 5:245-251. Hanke H, Hassenstein S. Kamenz J. et al. Time course of smooth muscle cell proliferation following intravascu- lar stenting and balloon angioplasty. (abstract) Eur Heart J 1992; 13:6. Puel J , Marco F, Debbas N , et al. Five years follow-up of the first intracoronary stents implanted in humans. (abstract) Eur Heart J 1992; 1 3 5 . Kiemeneij F. De Jaegere P, Morel MA, et al. The Bene- tent Study: Procedural results and clinical events during hospital stay. Lessons of the pilot phase. (abstract) Eur Heart J 1992: 1 3 5 . De Jagere P, Sermys PW, Bertrand M, et al. Angio- graphic predictors for restenosis following Wiktor stent implantation. Results of the European Registry and of

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

the Core lab for quantitative coronary angiography. (ab- stract) Eur Heart J 1992; 13:6. Mehta S, Margolis JR, Trautwein R, et al. Excimer laser coronary angioplasty is superior to PTCA for treating calcified lesions. (abstract) Eur Heart J 1992; 13:35. Kvasnicka J , Geschwind HJ, Nakamura F. Assessment of ablation efficiency and tissue damage induced by var- ious multiple fibre catheters. (abstract) Eur Heart J 1992; 1 3 5 3 . Mehta S, Margolis JR, Trautwein R, et al. Excimer laser coronary angioplasty: Single institution experience with 500 lesions. (abstract) Eur Heart J 1992; 13:380. The European Study Group for coronary excimer laser angioplasty. First quantitative results of the European coronary excimer laser angioplasty registry. (abstract) Eur Heart J 1992; 13:380. Keany JF, Bittl JA, Ryan TJ, et al. Risk of coronary artery perforation during excimer laser coronary angio- plasty: Multivariate analysis. (abstract) Eur Heart J 1992; 13:381. Kvasnicka J, Geschwind HJ, Duport G, et al. Influence of catheter size on the efficiency of excimer laser coro- nary angioplasty: Results from the French Registry. (ab- stract) Eur Heart J 1992; 13:381. Preisack MB, Baumbach A, Riessen R, et al. Predictors of acute closure following coronary excimer laser angio- plasty. (abstract) Eur Heart J 1992; 13:253. Di Mario C, de Jaegere P, Strikwerda S, et al. The use of steerable Doppler guidewire for coronary balloon an- gioplasty allows continuous monitoring of the procedure and immediate evaluation of the results. (abstract) Eur Heart J 1992; 13:35. The VA Coronary Artery Bypass Surgery Cooperative Study Group. Eighteen-year follow-up in the Veterans Affairs Cooperative study of Coronary Artery Bypass Surgery for Stable Angina. Circulation 1992; 86:

Hoffmann KK, Weber DJ, Samsa GP, et al. Transparent polyurethane film as an intravenous catheter dressing.

12 I - 130.

A meta-analysis of infection rates. J Am Med Assoc 1992 ; 267:2072-2076. Cobb DK, High KP, Sawyer RG, et al. A controlled trial of scheduled replacement of central and pulmonary- artery catheters. N Engl J Med 1992; 327;1062-1068.

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