Prevention of restenosis future directions.

Restenosis remains the major limitation of percutaneous transluminal coronary angioplasty. Restenosis after balloon angioplasty is due to vascular remodeling and neointimal hyperplasia. In spite of encouraging results in animal models, most of the pharmacological trials of prevention of restenosis in humans have produced negative results. This has prompted interest in the potential role of locally delivered drugs and various balloon catheter systems that are now available to achieve local delivery of therapeutic agents at the site of arterial injury. In 1997, implantation of a coronary stent in conjunction with balloon angioplasty is performed in an increasing number of patients. Randomized studies have shown that coronary stenting may reduce the risk of restenosis. In addition, restenosis after coronary stenting is mainly due to neointimal hyperplasia. Restenosis within coronary stents might thus be much more sensitive to therapies designed to inhibit neointimal hyperplasia than restenosis after balloon angioplasty. Thus, the future prevention of restenosis might well be the combination of a mechanical device that produces the widest possible lumen and prevents vessel constriction with a pharmacologic approach to inhibit the proliferative process. (Trends Cardiovasc Med 1997;7:90-94). © 1997, Elsevier Science Inc.

Cardiac resynchronisation therapy reduces functional mitral regurgitation during dynamic exercise in patients with chronic heart failure: an acute echocardiographic study.

OBJECTIVES: To assess non-invasively the acute effects of cardiac resynchronisation therapy (CRT) on functional mitral regurgitation (MR) at rest and during dynamic exercise. METHODS: 21 patients with left ventricular (LV) systolic dysfunction and functional MR at rest, treated with CRT, were studied. Each patient performed a symptom-limited maximal exercise with continuous two dimensional Doppler echocardiography twice. The first exercise was performed with CRT; the second exercise was performed without CRT. Mitral regurgitant flow volume (RV), effective regurgitant orifice area (ERO) and LV dP/dt were measured at rest and at peak exercise. RESULTS: CRT mildly reduced resting mitral ERO (mean 8 (SEM 2) v 11 (2) mm(2) without CRT, p = 0.02) and RV (13 (3) v 18 (3) ml without CRT, p = 0.03). CRT attenuated the spontaneous increase in mitral ERO and RV during exercise (1 (1) v 9 (2) mm(2), p = 0.004 and 1 (1) v 8 (2) ml, p = 0.004, respectively). CRT also significantly increased exercise-induced changes in LV dP/dt (140 (46) v 479 (112) mm Hg/s, p < 0.001). CONCLUSION: Attenuation of functional MR, induced by an increase in LV contractility during dynamic exercise, may contribute to the beneficial clinical outcome of CRT in patients with chronic heart failure and LV asynchrony.

Prospective evaluation of high-dose or low-dose isoproterenol upright tilt protocol for unexplained syncope in young adults.

The sensitivity of the passive head-up tilt test (HUT) in the evaluation of unexplained short-lasting syncope in young adults remains insufficient. The infusion of isoproterenol was proposed to improve the benefit. To evaluate the sensitivity-specificity relationship during isoproterenol dosing, we studied 76 young adults (aged 20.9 +/- 1.7 years) (group S) with recurrent (mean 3.8 +/- 1.6) losses of consciousness that remained unexplained after clinical and noninvasive assessment and 35 young healthy volunteers (aged 22.6 +/- 2.7 years) (group V). Subjects underwent either passive HUT (45 min, 60 degrees without drug dosing for 48 subjects in group S (S1) and 17 in group V (V1), or HUT with isoproterenol infusion at progressive doses (2 then 5 micrograms/min) after 30 minutes of passive tilting for 28 patients in group S (S2) and 18 in group V (V2). During passive HUT, the test was positive (asystole, bradycardia, or fall in systolic blood pressure) in 2 of 17 (11.8%) patients in group V1 and in 7 of 48 (14.6%) in group S1 before 30 minutes, and in 3 of 17 (17.6%) in group V1 compared with 10 of 48 (20.8%) in group S1 at the end of the 45-minute infusion, with no difference in delay before the appearance of a positive result. During HUT with isoproterenol dosing, the test was positive in 2 of 18 (11.1%) patients in group V2 and in 18 of 28 (64.2%) in group S2 before 45 minutes (2 micrograms/min; p < 0.01) in 7 of 18 (38.8%) in group V2 compared with 24 of 28 (85.7%) in group S2 before 60 min (5 micrograms/min; p < 0.01). In both cases the mean delay in evoking a positive response was significantly shorter. No asystolic response was observed in the volunteers regardless of the protocol used. The most characteristic response to isoproterenol injection was the appearance of a junctional escape rate with a fall in systolic blood pressure (61.5% of subjects in group S2). The infusion of isoproterenol considerably improves the sensitivity of the HUT with satisfactory specificity if low doses are used (< 3 micrograms/min). These results support the use of HUT with isoproterenol in the evaluation of unexplained syncope in young adults.