Review of percutaneous therapy for bifurcation lesions in the era of drug-eluting stents.

Although recent advances in percutaneous coronary interventions (PCI) have led to dramatic expansions in procedural complexity, bifurcation lesions (BL) remain a serious challenge for the interventionalist. Turbulent flow dynamics and high shear stress likely predispose coronary bifurcations to development of atherosclerotic plaques. These lesions comprise 15% to 20% of the total number of coronary interventions. When compared with non-BL interventions, BL interventions demonstrate lower procedural success rates, higher procedural costs, longer hospitalizations, and higher clinical and angiographic restenosis rates. The recent introduction of drug-eluting stents (DES) has resulted in lower incidences of target lesion/ vessel revascularization and reduction of main branch restenosis in this anatomic subset, when compared to historical bare metal stent (BMS) controls. Nonetheless, DES have not resolved the bifurcation PCI problem; and several techniques employing either 1 or 2 stents have emerged. Stenting of the main vessel with provisional side branch stenting seems to be the prevailing approach. While no definitive single BL-PCI technique has been identified, the optimal approach is likely lesion-specific. This paper reviews different treatment modalities for this complex lesion subset, with particular emphasis on the use of DES, as well as new potential therapeutic approaches.

[Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy].

BACKGROUND: The results of recent studies suggest that nitric oxide (NO) synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. METHODS AND RESULTS: We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined left ventricular contractility (Emax, the slope of end-systolic pressure-volume relation), left ventricular external work (EW), myocardial oxygen consumption (MVO2), and mechanical efficiency (measured as EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4.8 +/- 0.3 micrograms.kg-1.min-1 i.v.). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 200 mumol). DOB increased Emax, EW, and MVO2 (by 77 +/- 17%, 39 +/- 5%, and 21 +/- 5%, respectively), leading to an increase in mechanical efficiency (25.4 +/- 3.1% to 29.6 +/- 4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased Emax, EW, and MVO2 (by 140 +/- 21%, 64 +/- 9%, and 35 +/- 5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3 +/- 3.3% to 29.5 +/- 4.5%) because EW and MVO2 increased in parallel. CONCLUSIONS: These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO2 through attenuation of left ventricular contractile response to beta-adrenergic stimulation while maintaining left ventricular energy-converting efficiency.

Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. METHODS AND RESULTS: We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E(max), the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MVO(2)), and mechanical efficiency (measured as EW/MVO(2)) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4. 8+/-0.3 microg. kg(-1). min(-1) IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 200 micromol). DOB increased E(max), EW, and MVO(2) (by 77+/-17%, 39+/-5%, and 21+/-5%, respectively), leading to an increase in mechanical efficiency (25.4+/-3.1% to 29.6+/-4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased E(max), EW, and MVO(2) (by 140+/-21%, 64+/-9%, and 35+/-5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3+/-3.3% to 29.5+/-4.5%) because EW and MVO(2) increased in parallel. Conclusions-These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO(2) through attenuation of LV contractile response to beta-adrenergic stimulation while maintaining LV energy-converting efficiency.

Beneficial effects of heart rate reduction on cardiac mechanics and energetics in patients with left ventricular dysfunction.

It has been shown recently that the force-frequency relationship is blunted in experimental heart failure models. Furthermore, tachycardia is thought to have adverse effects on the diseased heart for several reasons, one of which is an increase in myocardial oxygen consumption. Inversely, the oxygen-saving effects of bradycardia may be beneficial for the treatment of heart failure. The aim of this study was to elucidate how heart rate (HR) modulates cardiac mechanics and energetics in patients with left ventricular (LV) dysfunction. LV pressure-volume data and myocardial oxygen consumption (MVO2) was assessed using conductance and coronary sinus thermodilution catheters in 14 patients with moderate LV dysfunction (mean ejection fraction 34%) under 3 conditions: (a) basal, (b) HR increased by 20% using atrial pacing, and (c) HR decreased by 16% using a specific bradycardic agent, zatebradine (7.5 mg p.o.). Atrial pacing decreased external work (EW) (from 0.39 to 0.31 J beat(-1) m(-2), p<0.05) at a comparable MVO2 per beat with a marginal increase in LV contractility index (Ees) (from 2.34 to 2.76 mm Hg ml(-1) m(-2), p = 0.08), resulting in a decrease in mechanical efficiency (EW/MVO2) (from 25.9 to 22.1%, p<0.05). In contrast, zatebradine did not decrease Ees (from 2.34 to 2.24 mm Hg ml(-1) m(-2), NS), but increased EW (from 0.39 to 0.42 J beat(-1) m(-2), p<0.05 vs. basal level) without a change in MVO2 per beat, resulting in improved mechanical efficiency (from 25.9 to 29.7%, p<0.05 vs. basal level). These results suggest that mild bradycardia is energetically advantageous and does not decrease myocardial contractility and performance, whereas pacing-induced tachycardia worsens cardiac mechanics and energetics in patients with LV dysfunction. Thus, the oxygen-saving effect of bradycardia may be beneficial for the treatment of heart failure.