School of Pharmaceutical Sciences, Jaipur National University, Jaipur (Raj.), India
Background: The nonsurgical treatment of arteries narrowed by atherosclerosis was introduced in 1964, when Dotter and Judkin performed transluminal angioplasty of femoral artery stenoses. In 1970, Gruntzig modified the dilation catheter to allow its use in coronary arteries dilation. Subsequently, In 1977 he performed the first Percutaneous Transluminal Coronary Angioplasty (PTCA) in a patient. Since onward, PTCA has been used in many patients with stable angina, unstable angina or acute myocardial infarction. Its use was initially limited to the treatment of discrete stenoses in proximal segment of a coronary artery, but improvements in equipments and techniques have lead its use in patients with stenoses, that are more complex or located in distal arterial segments and in patients relatively at high risk for complications. Despite the wider application of PTCA, the success rate remained high. Over the past decade, the number of procedure performed has steadily increased, with over 300,000 performed in united state in 1990.
Short- Term Complications:
Although PTCA is genrerally safer, complication occasionally occurs
including myocardial infarction in 3 to 5 percent[5,6], Yet
it is need for emergency bypass surgery in 3 to 7 percents[7,8]
and death in 0 to 2 percent[9,10]. These event usually caused by
extensive coronary arterial dissection, intracoronary thrombosis,
or both, with resultant vessel occlusion. Coronary arterial perforation,
rupture, or remobilization is rare. The last is more likely in a
sphenous- vein graft than in a native vessel.
Acute or abrupt closure occurs in 2 to 8 percent of patients undergoing PTCA[11,12], and accounts for most of the short – term morbidity and mortality associated with the procedure. In about 75% of patients with abrupt closure, it occurs within minutes after PTCA, when they are still in the catheterization laboratory; in the other 25 percent it usually occurs within 24 hours after the procedure .
Mechanism of Abrupt Closure:
Three pathophysiologic processes may contribute to the occurrence
of abrupt closure after PTCA: extensive dissection, thrombosis,
and coronary vasospasm. Some degree of intimal dissection-
characterized angiographically as a linear interaluminal
filling defect or flap associated with a hazy, ground glass appearance-
is frequently observed after successful PTCA. When the dissection
is limited, its angiographic characteristics may be subtle
and evident only on selected views. However, when it is extensive,
the radiographic features are readily apparent, and the vessel lumen
may be compromised. 10 % of patients with coronary arterial
dissection after PTCA require emergency bypass surgery, sustain a
myocardial infarction, or die. In contrast, less than 2 % of patients
without extensive dissection have a serious complication.
Acute thrombus formation after PTCA is characterized angiographically as an intraluminal filling defect or an area stained with radiographic contrast material. Thrombus formation is most likely to occur in patients with extensive dissection, those with a severe residual stenosis after PTCA, those with pre-existing intracoronary thrombus, and those not receiving an antiplatelet agent. In One study, 22% of the patients undergoing PTCA without antiplatelet therapy had thrombi, demonstrable by angiography after dilation. In half of these patients, the thrombi caused occlusion, requiring repeated PTCA, bypass surgery, or thrombolysis. Conversely, those who received aspirin before PTCA were much less likely to have demonstrable thrombi afterward. Since; most patients receive nitrates, calcium-channel blockers, or both before, and after PTCA, coronary vasospasm is an uncommon cause of abrupt closure.
Risk Factors for Abrupt Closure:
Several clinical, anatomical, and procedural variables are associated with an increased incidence of abrupt closure after PTCA. The influence of these variables is cumulative: the more variables that are present in a particular case, the greater the likelihood of abrupt closure
Consequences of Abrupt Closure:
The consequences of abrupt closure vary widely. Patients with adequate
collateral perfusion of the occluded vessel may have abrupt
chest pain, electrocardiographic abnormalities, or hemodynamic
compromise. More commonly, abrupt closure is accompanied by
chest discomfort and electrocardiographic evidence of ischemia
and requires immediate revascularization of the occluded vessel to
prevent or limit myocardial injury.
The common Variables associated with an increased risk of abrupt closure of the artery in patients undergoing PTCA may be clinical, such as; female sex, unstable angina, MVD or Anatomical such as; angiographically demonstrable intracoronary thrombus, eccentric stenosis, stenosis located at or near a bend or branch, severe pre PTCA stenosis, stenosis or 2 luminal diameter in length, sequential stenosis, diffusely diseased artery, procedural variables, extensive coronary arterial dissection and use of oversized balloon.
Management of Abrupt Closure:
Since the most effective treatment of abrupt closure is prevention,
strategies aimed at precluding its possible causes (dissection,
thrombosis, and vasospasm) are routinely instituted. Calciumchannel
blockers, nitrates, or both are usually administered before,
during, and after PTCA, even though no controlled study has
shown that they reduce the incidence of abrupt closure. All patients
receive aspirin before and after PTCA, and all are given heparin
during the procedure, with the adequacy of anticoagulation monitored.
In many centres, patients at high risk of abrupt closure are
given infusion of heparin for 12 to 24 hours after PTCA, although
the efficacy of this approach has not been proved. Only aspirin has
been shown to reduce the incidence of abrupt closure.
When abrupt closure occurs, redilation with a standard balloon catheter is usually attempted, which is successful in about 50 percent of patients[ 24]. When this strategy fails, a special balloon catheter may be used, if the coronary anatomy is suitable. Holes in the catheter proximal and distal to the balloon allow blood to flow through the catheter during inflation of the balloon, thus maintaining perfusion of the distal artery during prolonged inflation. In the majority of patients in whom a standard balloon catheter fails to restore sustained anterograde perfusion, a perfusion catheter is effective.
Peripheral vascular complications, such as arterial pseudoaneursym, laceration, anteriovenous fistula, embolism, arterial occlusion and hematoma formation, occur in about 3 %t of patients undergoing PTCA. The use of large arterial sheaths, the concomitant use of anticoagulant or thrombolytic therapy, an advanced age, and the presence of peripheral vascular disease increase the risk of these vascular complications. Other less common acute complications of PTCA are similar to those of diagnostic coronary angiography, including arterial or ventricular arrhythmias, conduction abnormalities, coronary arterial embolization, cardiac tamponade, allergic reactions to contrast material or one of the medications given during PTCA, vasovagal episodes, and cerebrovascular embolization resulting in anuerologic deficit[25, 26].
Long Term- Complications:
In patients who have undergone successful PTCA, the chief limitation on long term, event- free survival is recurrence of the stenosis, or restenosis. Although improved medical therapy and technical advances over the past decade have reduced the incidence of abrupt closure, the incidence of restenosis has not changed. Several definitions of restenosis have been suggested, but it is most commonly defined as more than 50 % narrowing of the diameter lumen at the site previously successful PTCA. Restenosis occurs in about 60% of those whom a chronically occluded artery has been dialated[27, 28, 29, 30] . Restnosis occurs in one to three month’s afterPTCA, and in 95 percent of patients, it occurs within six months after the procedure. Restenosis is uncommon less than one month or more than six months after PTCA.
Mechanism of Restenosis:
The process of restenosis is initiated by injury of the vessel, with the subsequent release of thrombigenic, vasoactive, and mitogenic factors. Endothelial and deep vessel injury leads platelet aggregation, thrombus formation, inflammation, and activation of macrophages. These events induce production and release of growth factors and cytokines, which in turn may promote their own synthesis and release from target cells. Thus, a perpetuating process is initiated, which results the migration of smooth muscle cells from their usual location in the arterial media to the intima, where they change to a synthetic phenotype, produce extracellular matrix, and proliferate, thereby resulting in a stenosis within the vessel lumen. In addition, scar contraction may occur, further reducing the size of the lumen. These processes make up the wound healing response that occurs in all patients undergoing PTCA. In patients with the most pronounced reparative response to the intimal and medial damage induced by balloon inflation, luminal encroachment is particularly marked, and such patients are said to have restenosis. Contraction of the dialated and stretched medial and adventitial layers- so called elastic recoil- may contribute to restenosis, but such contraction is usually apperent within hours to days after PTCA.
Risk Factors for Restenosis:
Numerous clinical, anatomical, and procedural variables have been associated with an increased incidence of restenosis after successful PTCA. The common clinical variables are male sex , cigarette smoking, diabetes mellitus, hypertension , hypercholestromia, renal disease, vasospatic angina and unstable angina[40, 41]. Among the clinical variables, diabetes mellitus and unstable angina are reported most frequently. The anatomical variables such as; proximal stenosis, saphenous- vein graft involvement of the left anterior descending artery, chronically occluded artery, stenosis more 5 to 10 mm in length, severe pre PTCA stenosis[42,43,44], and procedural variable such as residual stenosis, small residual lumen, and used undersized balloon may increase incidences of restenosis after PTCA.
Consequences of Restenosis:
Most patients with restenosis after successful PTCA have recurrent angina, but some of those with angiographic evidence of restenosis are asymptomatic. Since such patients have a good prognosis, a second angioplasty should be reserved for those recurrent symptoms . Myocardial infarction is rarely the initial manifestation of restenosis. The severity of narrowing at the site of restenosis is usually similar to that PTCA. However, when PTCA is performed in a minimally narrowed coronary artery, the restenosis may be more severe than initial stenosis.
Management of Restenosis:
Restenosis is often treated successfully with a second PTCA. The second procedure is more likely to be successful than the first and less likely to be associated with an acute complication. Probably a second procedure is performed only in patients in whom first was successful, and because the restenosis consist primarily of fibro proliferative tissue rather than atherosclerotic plaque. Numerous pharmacological approaches and devices have been evaluated in an attempt to prevent restenosis. Fish oil, and trapidil (growth inhibitor) have shown promise in some trials[48, 49]. Some trials that failed to demonstrate the benefit of a particular pharmacologic agent may have too few patients and uses adequate doses. The incidence of restenosis after elective placement of an intracoronary stent appears to be low[50, 51], but the result of randomized trials comparing the use of a stent with PTCA alone are not yet available.
Since the introduction of PTCA is more than 15 years ago, there have been notable advances in technique and equipment. Many stenosis; regardless of their location, severity, or morphologic characteristics, can now be dilated successfully. The development of devices should make it possible to expand the use of PTCA even further. Moreover, new antiplatelet and antithrombin agents may reduce the incidence of acute thrombotic complications. Restenosis remains challenge unfortunately; there has been little progress in reducing its incidence. The physiology of restenosis is multifactorial and poorly understood. In all probability, therapeutic approach that several pharmacologic and procedural innovations will be required to decrease the incidence of restenosis.
- Dotter CT and Judkins MP. Transluminal treatment of arteriosclerotic obstruction: description of new technique and a preliminary report of its application, Circulation. (1964); 30: 654 -670.
- Gruntzig A. Transluminal dilation of coronary- artery stenosis. Lancet (1978); 1: 263.
- Deter K, Holubkov R, Kelsey S. Percutaneous Transluminal Coronary Angioplasty in 1985- 1986 and 1977- 1981. The National Heart, Lung and blood institute registry. N Engl J Med (1988); 318:265-370.
- Topol EJ, Ellis SG, Cosgrove DM. Analysis of coronary angioplasty practice in United States with insurance –claim data base. Circulation. (1993); 87: 1489-1497.
- Parisi AF, Folland ED, Hartigan P. A comparison of angioplasty with medical therapy in the treatment of single vessel coronary artery disease. N Engl J Med (1992); 326 (1):10-16.
- Myler RK, Shaw RE, Stertzer SH, Bashour TT, Ryan C, Hecht HS. Unstable angina and coronary angioplasty. Circulation (1990); 82: 88-95.
- Williams DO, Braunwald E, Knatterud G. One year result of the thrombolysis in myocardial infarction investigation (TIMI) phase 2 trail. Circulation (1992); 85:533-542.
- Talley JD, Weintraub WS, Roubin GS. Failed elective percutaneous transluminal coronary angioplasty requiring coronary artery bypass surgery: in hospital and late clinical outcome at 5 years. Circulation (1990); 82:1203-1213.
- Hartz AJ, Kuhn EM, Pryor DB, Krakauer H, Young M, Heudebert G, Rimm AA. Mortality after coronary angioplasty and coronary artery bypass surgery (The national Medicare experience). Am J Cardiol (1992); 70: 179-185.
- Myler RK, Stertzer SH, Ryan C, Cumberland DC, Hansell HN. Lesion morphology and coronary angioplasty: Current experience and analysis. J Am Coll Cardiol (1992); 19 (7):1641-1652.
- Ellis SG, Rubin GS, King SB. Angiography and clinical predictors of acute closure after native vessel coronary angiography. Circulation (1988); 77:372-379.
- Sinclair IN, McCabe CH, Sipperly ME, Bairn DS. Predictors, therapeutic options and long term outcome of abrupt closure. Coronary angioplasty. AM. J.Cardiol (1988); 61:61C-66C.
- Lincoff AM, Popma JJ, Ellis SG, Hacker JA, Topol EJ. Abrupt vessel closure complicating coronary angioplasty: clinical angiographic and therapeutic profile. J am Coll Cardiol (1992); 19 (5): 926-935.
- Mabin TA, Smith HC, Bove AA, Chesebro JH, Orszulak TA. Intracoronary thrombus: Role in coronary occlusion complicating percutanous coronary angioplasty. J Am Cool Cardiol (1985); 5 (2):198-202.
- Bredlau CE, Roubin GS, Leimgruber PP, Douglas JS, King SB, Gruentzig AR. In –hospital morbidity and mortality in patients undergoing elective coronary angioplasty. Circulation (1985); 72 (5):1044-1052.
- Baranathan ES, Schwartz JS, Taylor L, Laskey WK, Kleaveland JP, Kussmaul WG, Hirshfeld JWJ. Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty. Circulation (1987);76(1):125-134.
- Deter KM, Holmes DR, Holubkov R. Incidence and consequences of periprocedural occlusion: The 1985-1986 National Heart, Lung and Blood institute Percutaneous Transluminal coronary Angioplasty registry. Circulation (1990); 82: 739-750.
- De Feyter PJ, Van den Brand M, Laarman GJ. Acute coronary artery occlusion: during and after percutaneous transluminal coronary: Frequency, prediction, clinical course, management, and follow- up. Circulation (1991); 83: 927-936.
- Elis SG and Eric JT. Results of percutaneous transluminal coronary angioplasty of high- risk angulated stenoses. Am J Cardiol (1990); 66: 932-937.
- Simpfendorfer C, Belardi J, Bellamy G. Frequency, management and follow up of patients with acute coronary occlusions after percutanous transluminal coronary angioplasty. Am J Cardiol (1987); 59:267-269.
- Savage MP, Goldberg S, Hirshfeld JW. Clinical and angiographic determinants of primary coronary angioplasty success. J Am Coll Cardiol (1991); 17:22-28.
- Roubin GS. Douglas JS, King SB, Lin S, Hutchison N, Thomas RG, Gruentzig AR. Influence of balloon size on initial success, acute complications, and restenosis after percutaneous transluminal coronary angioplasty: a prospective randomized study. Circulation (1988); 78:557-565.
- Schwartz L, Bourassa MG, Lespérance J, Aldridge HE, Kazim F, Salvatori VA, Henderson M, Bonan R, David PR. Aspirin and dipyridamole in the prevention of Re-stenosis after percutaneous transluminal coronary angioplasty. N Engl J Med (1988);318:1714-1719
- Leitschuh ML, Miffs RM, Jacobs AK. Outcome after major dissection during coronary angioplasty using the balloon catheter. Am J Cardiol (1991); 67: 1056-60.
- Muller DWM. Peripheral vascular complications after conventional and complex percutaneous coronary interventionational procedures. Am J Coll Cardiol (1992); 69:63-68.
- Oweida SW, Roubin GS, Smith RB, Salam AA. Postcatheterization vascular complications associated with percutaneous transluminal coronary angioplasty. J. Vasc surg (1990); 12:1400-1405.
- Gruentzing AR, King SBIII, Schlumpf M, Siegenthaler W. Long-term follow-up after percutaneous transluminal coronary angioplasty: The early experience. N Engl J Med (1987), 316: 1127–1132.
- Leimgruber PD, Roubin GS, Hollman J. Restenosis after successful coronary angioplasty in patients with single-vessel disease. Circulation (1986); 73:710-717.
- Meracator study group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis afterPTCA? Results of the meracator study: a multicenter, randomized, double blind placebo- controlled trail. Circulation. (1992); 86:100-110.
- Hirshfeld JW, Schwartz S, Jugo R, Macdonald RG, Goldberg S, Savage MP et al. Re-stenosis after coronary angioplasty: a multivariate stastical model to relate lesion and procedure variable to resenosis. J Am Coll Cardiol (1991); 18:647-656.
- Nobuyoshi M, Kimura T, Nosaka H, Mioka S, Ueno K, Yokoi H, Hamasaki N, Horiuchi H, Ohishi H. Restenosis after successful PTCA: serial angiography follows up of 229 patients. J Am Coll Cardiol (1988); 12 (3):616-623.
- Lange RA and Richard A. Restenosis; the Achilles heel of coronary angioplasty. Am J Med Sci (1993):306:265-275.
- Libby P, Schwartz D, Brogi E, Tanaka H, Clinton SK. A cascade model for restenosis: a special case of artherosclerosis progression. Circulation (1992); 86 (6):47-52.
- Haude M, Erbel R, Issa H, Meyer J. Quantitative analysis of elastic recoil after balloon angioplasty and after intracoronary implantation of balloon- expandable palmaz-schatz stents. J Am Coll Cardiol (1993); 21(1): 26-34.
- Holmes DR Jr, Vlietstra RE, Smith HC. Restenosis after PTCA: A report from PTCA registry of the National Heart, Lung and Blood institute. Am J Cardiol 1984; 53 (12) : 77-81.
- Galan KM, Deligonul U, Kern MJ. Increased frequency of restenosis in patients continuing the smoke, cigarettes after PTCA. Am J Coll Cardiol (1988); 61:260-263.
- Austin GE, Lynn, MS, Hollman, J. Laboratory test results as predictors of recurrent coronary artery stenosis following angioplasty. Am J Cardiol (1988); 111:1158-1162.
- Weintraub WS, Kosinski AS, Brown CL, King III SB. Can restenosis after PTCA be predicted from clinical variables? J Am Coll Cardiol (1993); 21:6-14.
- Reis GJ, Kuntz RE, Silverman DI, Pasternak RC. Effects of serum lipids levels on restenosis after PTCA. Am J Cardiol (1991); 68:1431-35.
- Kahn JK, Rutherford BD, McConahay DR, Johnson WL, Giorgi LV, Hartzler GO. Short- and long-term outcome of percutaneous transluminal coronary angioplasty in chronic dialysis patients. Am Heart J. 1990; 119: 484–489
- Guiteras VP, Bourassa MG, David PR. Restenosis after successful PTCA: the Montreal Heart Institute experience. Am J Cardiol (1987); 60: 50-55.
- Vandomael MG, Deligonul U, Kern MJ, Harper M, Presant S, Gibson P, Galan K, Chaitman BR. Multilesion coronary angioplasty: clinical and angiographic follow- up. J Am Coll Cardiol, (1987); 10: 246-52.
- Roubin GS. Restenosis after PTCA: The Emroy University Hospital experience. Am J Cardiol (1987); 60:39-43.
- De Feyter PJ, Suylen RJV, De Jaegere PPT, Topal EJ, Serruys pw. Balloon angioplasty for the treatment of lesions in saphenous vein bypass grafts. J Am Coll Cardiol (1993); 13: 1085-91.
- Nicholas AB, Smith R, Berke AD, Shlofmitz RA, Powers ER. Importance balloon size in coronary angioplasty. J Am Coll Cardiol (1989); 13 (5):1094-100.
- Hernandez RA, Macaya C, Iniguez A, Alfonso F, Goecolia J, Zarco P. Midterm outcome of patients with asyptomatic restenosis after coronary balloon angioplasty. J Am Coll Cardiol (1992);19:1402-9.
- Dehmer GJ, Popma JJ, van den Berg EK. Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. N Engl J Med (1988); 319: 733-740.
- Bairati I, Roy L, Meyer F. Controlled trial of fish oil supplement is suppliments in prevention of recurrence of stenosis after coronary angioplasty. Circulation, (1992); 85: 950-956.
- Sahni R, Maniet AR, Voci G. Prevention of restenosis by lovastatin after successful coronary angioplasty. Am Heart J (1919); 121:1600-1608.
- Serruys PW, Strauss BH, Beatt JK, Bertrand ME, Puel J, Rickards AF, Meier B, Goy JJ, Vogt P, Kappenberger,L, Sigwart U. Angiographic follow-up after placement of a self-expanding coronary- artery stent. N Engl J Med (1991); 324:13-17.
- Kimura T, Nosaka H,Yokoi H. Serial angiographic follow up after palmaz- schatz stent implantation: comparison with conventional balloon angioplasty. J Am Coll Cardiol (1993); 21:1557-63.