Fiore Manganelli

Acetylcysteine and contrast agent-associated nephrotoxicity

OBJECTIVESnProphylactic acetylcysteine along with hydration seems to be better than hydration alone in preventing the reduction in renal function induced by a contrast dye.nnnBACKGROUNDnContrast media can lead to acute renal failure that may occasionally require hemodialysis.nnnMETHODSnOne hundred eighty-three consecutive patients with impairment of renal function, undergoing coronary and/or peripheral angiography and/or angioplasty, were randomly assigned to receive 0.45% saline intravenously and acetylcysteine (600 mg orally twice daily; group A, n = 92) or 0.45% saline intravenously alone (group B, n = 91) before and after nonionic, low-osmolality contrast dye administration.nnnRESULTSnThe baseline serum creatinine concentrations were similar (1.5 +/- 0.4 mg/dl in group A vs. 1.5 +/- 0.4 mg/dl in group B; p = 0.37). An increase of > or =25% in the baseline creatinine level 48 h after the procedure occurred in 6 (6.5%) of 92 patients in group A and in 10 (11%) of 91 patients in group B (p = 0.22). In the subgroup with a low (<140 ml) contrast dose, renal function deterioration occurred in 5 (8.5%) of 60 patients in group B and in 0 of 60 patients in group A (p = 0.02; odds ratio [OR] 0.44, 95% confidence interval [CI] 0.35 to 0.54). In the subgroup with a high contrast dose, no difference was found (5/31 vs. 6/32 patients, p = 0.78). By multivariate analysis, the amount of contrast agent, but not the treatment strategy, was a predictor of the occurrence of contrast dye-associated nephrotoxicity (OR 2.58, 95% CI 1.1 to 4.9; p = 0.035).nnnCONCLUSIONSnIn patients with reduced renal function undergoing angiography and/or angioplasty, the amount of contrast agent, but not the administration of prophylactic acetylcysteine, was a predictor of renal function deterioration. Prophylactic acetylcysteine might provide better protection than hydration alone, only when a small volume of contrast agent is used.

Benefits of drug-eluting stents as compared to bare metal stent in ST-segment elevation myocardial infarction: Four year results of the PaclitAxel or Sirolimus-Eluting stent vs bare metal stent in primary angiOplasty (PASEO) randomized trial

BACKGROUNDnDrug-eluting stent (DES) may offer benefits in terms of repeat revascularization, which may be counterbalanced by a potential higher risk of stent thrombosis, especially among patients with STEMI. No data have been reported so far on the long-term benefits and safety of DES in STEMI. The aim of the current study was to evaluate the short- and long-term benefits of sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) as compared to bare-metal stent (BMS) in patients undergoing primary angioplasty.nnnMETHODSnConsecutive patients with STEMI admitted within 12 hours of symptom onset and undergoing primary angioplasty and stent implantation at a tertiary center with 24-hour primary percutaneous coronary intervention capability were randomly assigned to BMS, PES, and SES. All patients received upstream glycoprotein IIb-IIIa inhibitors. Primary end point was target-lesion revascularization at 1-year follow-up. Secondary end points were (1) cumulative combined incidence of death and/or reinfarction; (2) cumulative incidence of in-stent thrombosis; and (3) major adverse cardiac events (MACE) (combined death and/or reinfarction and/or target lesion revascularization [TLR]) at long-term follow-up (up to 4 years). No patient was lost to follow-up.nnnRESULTSnFrom October 1, 2003, to December 2005, 270 patients with STEMI were randomized to BMS (n = 90), PES (n = 90), or SES (n = 90). Procedural success was obtained in 93% to 95% of patients. Follow-up data were available for all patients. As compared to BMS (14.4%), both PES (4.4%, hazard ratio [HR] 0.29, 95% CI 0.095-0.89, P = .023) and SES (3.3%, HR 0.21, 95% CI 0.06-0.75, P = .016) were associated with a significant reduction in TLR at 1-year follow-up (primary study end point). At long-term follow-up (1,233 +/- 215 days), no difference was observed in terms of death, reinfarction, and combined death and/or reinfarction, but as compared to BMS (21.1%), both PES (6.7%, HR 0.29, 95% CI 0.12-0.73, P = .008) and SES (5.6%, HR 0.24, 95% CI 0.09-0.63, P = .002), respectively, were associated with a significant reduction in TLR.nnnCONCLUSIONSnThis study shows that among patients with STEMI undergoing primary angioplasty, both SES and PES are safe and associated with significant benefits in terms of TLR up to 4 years follow-up, as compared to BMS. Thus, until the results of further large randomized trials with long-term follow-up become available, DES may be considered among patients with STEMI undergoing primary angioplasty.

The PASEO (PaclitAxel or Sirolimus-Eluting Stent Versus Bare Metal Stent in Primary Angioplasty) Randomized Trial

OBJECTIVESnThe aim of this study was to evaluate the benefits of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) as compared with bare-metal stents (BMS) in patients undergoing primary angioplasty.nnnBACKGROUNDnRecent concerns have emerged on the potential higher risk of stent thrombosis after drug-eluting stent implantation, especially among ST-segment elevation myocardial infarction (STEMI) patients.nnnMETHODSnWe randomly assigned STEMI patients admitted within 12 h of symptom onset undergoing primary angioplasty and stent implantation to BMS, PES, or SES. The primary study end point was target lesion revascularization at 1-year follow-up. All patients were reviewed at our outpatient clinic or by telephone interview at 6, 12, and 24 months.nnnRESULTSnFrom October 2003 to December 2005, 270 STEMI patients undergoing primary angioplasty were randomized to BMS (n = 90), PES (n = 90), or SES (n = 90). No patient was lost to follow-up. As compared with BMS (14.4%), both PES (4.4%, p = 0.023) and SES (3.3%, p = 0.016) were associated with a significant reduction in target lesion revascularization at 1-year follow-up. At 2-year follow-up no difference was observed in terms of death, reinfarction, and combined death and/or reinfarction, but as compared with BMS, both PES and SES were associated with significant benefits in major adverse cardiac events (PES: 16.7%, p = 0.015; SES: 15.6%, p = 0.009, respectively).nnnCONCLUSIONSnThis study shows that among STEMI patients undergoing primary angioplasty, both SES and PES are safe and associated with significant benefits in terms of target lesion revascularization up to the 2-year follow-up. Thus, until the results of further large randomized trials with long-term follow-up become available, drug-eluting stents may be considered for STEMI patients undergoing primary angioplasty. (PaclitAxel or Sirolimus-Eluting Stent versus Bare Metal Stent in Primary Angioplasty [PASEO] Randomized Trial; NCT00759850).

Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.

Hemodynamic determinants of exercise-induced abnormal blood pressure response in hypertrophic cardiomyopathy

OBJECTIVESnWe sought to assess the hemodynamics of exercise in patients with hypertrophic cardiomyopathy (HCM), with and without an exercise-induced abnormal blood pressure (BP) response, by ambulatory radionuclide monitoring of left ventricular (LV) function with the VEST device (Capintec Inc., Ramsey, New Jersey).nnnBACKGROUNDnBlood pressure fails to increase >20 mm Hg during exercise in about one-third of patients with HCM. This carries a high risk of sudden death.nnnMETHODSnForty-three patients with HCM and 14 control subjects underwent maximal symptom-limited exercise on a treadmill during VEST. The VEST data were averaged for 1 min and analyzed at baseline, 3 min and peak exercise. The LV end-diastolic, end-systolic and stroke volumes, cardiac output and systemic vascular resistance were expressed as the percentage of baseline.nnnRESULTSnEjection fraction and stroke volume fell in patients with HCM, although they increased in control subjects (p < 0.001 and p = 0.002, respectively). Cardiac output increased significantly more in control subjects than in patients with HCM (p = 0.001). In 17 patients with HCM (39%) with an abnormal BP response, ejection fraction and stroke volume fell more (p = 0.032 and p = 0.009, respectively) and cardiac output increased less (p = 0.001) than they did in patients with HCM with a normal BP response. Systemic vascular resistance decreased similarly in patients with HCM, irrespective of the BP response.nnnCONCLUSIONSnIn patients with HCM with and without an abnormal BP response, abnormal hemodynamic adaptation to exercise was qualitatively similar but quantitatively different. An abnormal BP response was associated with exercise-induced LV systolic dysfunction. This causes hemodynamic instability, associated with a high risk of sudden cardiac death.

Noninvasive Evaluation of Left Ventricular Diastolic Function in Hypertrophic Cardiomyopathy

Diastolic dysfunction is common in hypertrophic cardiomyopathy (HC). Previous studies suggest that Doppler transmitral flow velocity profiles, and the left atrial (LA) M-mode echogram can be used noninvasively to evaluate left ventricular (LV) diastolic function. However, this has not been proved in HC. In this study we determined the relation of Doppler transmitral flow velocity profiles and the LA M-mode echograms to invasive indexes of LV diastolic function in patients with HC. We studied 25 patients with HC, while off drugs, and calculated LA global and active fractional shortening and the slope of both early and late displacement of the posterior aortic wall during LA emptying by M-mode echocardiography. We calculated peak velocity of early (E) and atrial (A) filling, E to A ratio, and E-wave deceleration time by pulsed Doppler echocardiography, and simultaneous radionuclide angiography, LV pressures, time constant of isovolumic relaxation tau, and the constant of chamber stiffness k by cardiac catheterization. The time constant of isovolumic relaxation tau correlated with the slope of early posterior aortic wall displacement (r = 0.59; p <0.01). LV end-diastolic pressure correlated with global LA fractional shortening (r = -0.75; p <0.001); the constant of chamber stiffness k correlated with active LA fractional shortening (r = -0.53; p <0.02). In a subset of 13 patients, in whom echocardiography and cardiac catheterization were performed simultaneously, similar results were found. LA M-mode recordings provide a more reliable noninvasive assessment of diastolic function in HC than mitral Doppler indexes.

Long-Term outcome of drug-eluting stents compared with bare metal stents in ST-segment elevation myocardial infarction: results of the paclitaxel- or sirolimus-eluting stent versus bare metal stent in Primary Angioplasty (PASEO) Randomized Trial.

BACKGROUNDnDrug-eluting stents may offer benefits in terms of repeat revascularization that may be counterbalanced by a potential higher risk of stent thrombosis, especially among ST-segment elevation myocardial infarction (STEMI) patients. No data have been reported so far on the long-term benefits and safety of drug-eluting stents in STEMI. Thus, the aim of the present study was to evaluate the short- and long-term benefits of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) compared with bare metal stents (BMS) in patients undergoing primary angioplasty.nnnMETHODS AND RESULTSnConsecutive STEMI patients admitted within 12 hours of symptom onset and undergoing primary angioplasty and stent implantation at a tertiary center with 24-hour primary percutaneous coronary intervention capability were randomly assigned to BMS, PES, or SES. All patients received upstream glycoprotein IIb/IIIa inhibitors. The primary end point was target lesion revascularization at the 1-year follow-up. Secondary end points were death and/or reinfarction, in-stent thrombosis, and major adverse cardiac events (combined death and/or reinfarction and/or target lesion revascularization) at long-term follow-up (up to 4 to 6 years). Cumulative incidence of end points was investigated. No patient was lost to follow-up. From October 1, 2003, to December 31, 2005, 270 patients with STEMI were randomized to BMS (n=90), PES (n=90), or SES (n=90). Procedural success was obtained in 93% to 95% of patients. Follow-up data were available for all patients. Compared with BMS (14.4%), both PES (4.4%; hazard ratio, 0.29; 95% confidence interval, 0.095 to 0.89; P=0.023) and SES (3.3%; hazard ratio, 0.21; 95% confidence interval, 0.06 to 0.75; P=0.016) were associated with a significant reduction in target lesion revascularization at the 1-year follow-up (primary study end point). At the long-term follow-up (4.3 years; 25th to 75th percentile, 3.7 to 5 years), no difference was observed in terms of death, reinfarction, and combined death and/or reinfarction, but compared with BMS (22.2%), both PES (6.7%; hazard ratio, 0.27; 95% confidence interval, 0.11 to 0.68; P=0.005) and SES (5.6%; hazard ratio, 0.22; 95% confidence interval, 0.083 to 0.59; P=0.003) were associated with a significant reduction in target lesion revascularization.nnnCONCLUSIONSnThis study shows that among STEMI patients undergoing primary angioplasty, both SES and PES are associated with significant benefits in terms of target lesion revascularization at the long-term follow-up compared with BMS with no excess risk of thrombotic complications. Thus, until the results of further large randomized trials with long-term follow-up become available, drug-eluting stents may be considered among STEMI patients undergoing primary angioplasty.

Effects of Diltiazem on Left Ventricular Systolic and Diastolic Function in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) is characterized by impaired diastolic function, and left ventricular (LV) outflow tract obstruction in about one-fourth of patients. Verapamil improves diastolic properties, but may have dangerous adverse effects. This study investigates the effects of diltiazem on hemodynamics and LV function in 16 patients with HC who were studied with cardiac catheterization and simultaneous radionuclide angiography. Studies were performed during atrial pacing (15 beats above spontaneous rhythm) at baseline and during intravenous diltiazem administration (0.25 mg x kg(-1) over 2 minutes, and 0.014 mg x kg(-1) x min(-1). Diltiazem induced a systemic vasodilation (cardiac index: 3.4 +/- 1.0 to 4.0 +/- 1.0 L x min(-1) x m(-2), p = 0.003; aortic systolic pressure: 116 +/- 16 to 107 +/- 19 mm Hg, p = 0.007; systemic resistance index: 676 +/- 235 to 532 +/- 193 dynes x s x cm(-5) x m(-2), p = 0.006), not associated with changes in the LV outflow tract gradient. The end-systolic pressure/volume ratio decreased (30 +/- 42 to 21 +/- 29 mm Hg x ml(-1) x m(-2); p = 0.044). Pulmonary artery wedge pressure (11 +/- 5 to 15 +/- 6 mm Hg, p = 0.006), and peak filling rate increased (4.1 +/- 1.3 to 6.0 +/- 2.4 stroke counts x s(-1), p = 0.004). The time constant of isovolumetric relaxation tau decreased (74 +/- 40 to 59 +/- 38 ms, p = 0.045). The constant of LV chamber stiffness did not change. Thus, active diastolic function is improved by the acute administration of diltiazem by both direct action and changes in hemodynamics and loading conditions. LV outflow tract gradient does not increase despite systemic vasodilation. In some patients, however, a marked increase in obstruction and a potentially harmful elevation in pulmonary artery wedge pressure do occur. Passive diastolic function is not affected.

Randomized Comparison of Everolimus-Eluting Stents and Sirolimus-Eluting Stents in Patients With ST Elevation Myocardial Infarction: RACES-MI Trial

OBJECTIVESnThe aim of the current study was to compare everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing primary angioplasty.nnnBACKGROUNDnDrug-eluting stents may offer benefits in terms of repeat revascularization. However, as shown for first-generation drug-eluting stents, they may be counterbalanced by a potential higher risk of stent thrombosis, especially among patients with ST-segment elevation myocardial infarction (STEMI). No data have been reported so far on the long-term benefits and safety of the new generation of drug-eluting stents in STEMI.nnnMETHODSnConsecutive STEMI patients admitted within 12 h of symptom onset and undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary percutaneous coronary intervention capability were randomly assigned to SES or EES. The primary endpoint was a major adverse cardiac event at 3-year follow-up. The secondary endpoints were death, reinfarction, definite or probable stent thrombosis, and target vessel revascularization at 3-year follow-up. No patient was lost to follow-up.nnnRESULTSnFrom April 2007 to May 2009, 500 patients with STEMI were randomized to EES (n = 250) or SES (n = 250). No difference was observed in terms of baseline demographic and clinical characteristics between the groups. No difference was observed between the groups in terms of number of implanted stents per patient or total stent length. However, a larger reference diameter was observed with SES (3.35 ± 0.51 mm vs. 3.25 ± 0.51 mm, p = 0.001), whereas patients randomized to EES more often received glycoprotein IIb/IIIa inhibitors (54.4% vs. 42.4%, p = 0.006). Follow-up data were available in all patients (1,095 ± 159 days). No significant difference was observed between EES and SES in major adverse cardiac events (16% vs. 20.8%, adjusted hazard ratio [HR]: 0.75 [95% confidence interval (CI): 0.5 to 1.13], p = 0.17), cardiac death (4.4% vs. 5.6%, adjusted HR: 0.77 [95% CI: 0.35 to 1.71], p = 0.53), recurrent MI (6.4% vs. 10%, adjusted HR: 0.62 [95% CI: 0.33 to 1.16], p = 0.13), and target vessel revascularization (4.8% vs. 4.8%, adjusted HR: 1.00 [95% CI: 0.45 to 2.32], p = 0.99). However, EES was associated with a significant reduction in stent thrombosis (1.6% vs. 5.2%, adjusted HR: 0.3 [95% CI: 0.1 to 0.92], p = 0.035).nnnCONCLUSIONSnThis study shows that among STEMI patients undergoing primary angioplasty, EES has similar efficacy as SES, but is associated with a significant reduction in stent thrombosis. (Randomized Comparison of Everolimus Eluting Stents and Sirolimus Eluting Stent in Patients With ST Elevation Myocardial Infarction [RACES-MI]; NCT01684982).

Impact of diabetes on long-term outcome in STEMI patients undergoing primary angioplasty with glycoprotein IIb-IIIa inhibitors and BMS or DES

Diabetes has been shown to be associated with worse survival and repeat revascularization (TVR) after primary angioplasty. Drug-eluting stent (DES) may offer benefits in terms of TVR, that may be counterbalanced by an higher risk of stent thrombosis, especially among STEMI patients. Aim of the current study was to evaluate the impact of diabetes on 5-year outcome in patients undergoing primary angioplasty with Glycoprotein IIb–IIIa inhibitors in the era of DES. Our population is represented by STEMI patients undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary PCI capability within 12 h of symptom onset. All patients received glycoprotein IIb–IIIa inhibitors. No patient was lost to follow up. From 2003 to 2005, 270 STEMI patients were treated with DES (nxa0=xa0180), or BMS (nxa0=xa090). A total of 69 patients had history of diabetes at admission (25.5%). At a follow-up of 1510xa0±xa0406xa0days, diabetes was associated with a higher rate of death (29.5 vs. 5.1%, Pxa0<xa00.0001), reinfarction (24.1 vs. 9.1%, Pxa0<xa00.0001), TVR (19.1 vs. 13.1%, Pxa0=xa00.052), IST (17.2 vs. 6.8%, Pxa0<xa00.001) and MACE (51.9 vs. 25.1%, Pxa0<xa00.001). These results were confirmed in both patients receiving BMS or DES, except for TVR, where no difference was observed between diabetic and non-diabetic patients. This study shows that among STEMI patients undergoing primary angioplasty with Gp IIb–IIIa inhibitors, diabetes is associated with worse long-term mortality, reinfarction, and IST, even with DES implantation, that, however, were able to equalize the outcome in terms of TVR as compared to non diabetic patients.