Paolo Pagnotta

Acute Anti-Ischemic Effect of Testosterone in Men With Coronary Artery Disease

BACKGROUND The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men. METHODS AND RESULTS After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05). CONCLUSIONS Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.

In-Stent Restenosis in Small Coronary Arteries Impact of Strut Thickness

UNLABELLED OBJECTIVES; We sought to evaluate whether strut thickness may impact the restenosis rate after stent implantation in small coronary arteries. BACKGROUND Small vessel size (<3.0 mm) is an independent risk factor for the occurrence of in-stent restenosis. It has been reported that vessel damage induced during stent deployment is an important factor in restenosis. METHODS From our database, we selected all patients who had successful stenting in small native vessels, with angiographic follow-up available, between March 1996 and April 2001. The strut was defined as thin when <0.10 mm and thick when > or = 0.10 mm. According to these criteria, we identified two subgroups: a thin group and a thick group. RESULTS A total of 821 (57%) of the 1,447 patients had angiographic follow-up available and were included in the analysis. The thin group included 400 patients with 505 lesions. The thick group included 421 patients with 436 lesions. The restenosis rate was 28.5% in the thin group and 36.6% in the thick group (p = 0.009; odds ratio [OR] 1.44, 95% confidence interval [CI] 1.09 to 1.90). The study group was classified into three subgroups according to the reference vessel diameter: < or = 2.50 mm, 2.51 to 2.75 mm and 2.76 to 2.99 mm. Strut thickness influenced the restenosis rate only in the subgroup with a reference vessel diameter between 2.76 and 2.99 mm, with rates of 23.5% in the thin group and 37% in the thick group (p = 0.006). By logistic regression analysis, predictors of restenosis were stent length (OR 1.03, 95% CI 1.01 to 1.04; p = 0.001), strut thickness (OR 1.68, 95% CI 1.23 to 2.29; p = 0.001) and diabetes mellitus (OR 2.10, 95% CI 1.21 to 3.68; p = 0.007). CONCLUSIONS This study supports that strut thickness is an independent predictor of restenosis in coronary arteries with a reference diameter of 2.75 to 2.99 mm.

First Clinical Experience With a Paclitaxel Derivate–Eluting Polymer Stent System Implantation for In-Stent Restenosis Immediate and Long-Term Clinical and Angiographic Outcome

Background—It has been shown that antiproliferative drugs such as paclitaxel lower the amount of intimal hyperplasia after stent implantation. We report the first clinical experience of 7-hexanoyltaxol (QP2)–eluting polymer stent system (QuaDS) implantation for in-stent restenosis. Methods and Results—Fifteen consecutive patients with elective indication to percutaneous coronary intervention for in-stent restenosis were treated with the QuaDS-QP2 stent implantation. The QuaDS-QP2 stent was successfully implanted in all but 2 target lesions. In one lesion, the restenotic segment could not be completely covered by the stent, and in another lesion, a bare metal stent was implanted distally to the QuaDS-QP2 stent. One patient suffered from postprocedural non–Q-wave myocardial infarction (NQWMI). No other adverse events were observed during hospital stay. Six- and 12-month angiographic and clinical follow-up was scheduled for all patients. At 6 months, 3 patients had target lesion revascularization (20%). Two patients had restenosis (13.3%); one experienced restenosis in a gap between 2 drug-eluting stents, and the other had stent occlusion leading to NQWMI. Minimal intimal hyperplasia was observed in all the segments covered by drug-eluting stents (late loss=0.47±1.01 mm with a loss index=0.17±0.39). At 12 months, 1 patient suffered from NQWMI, and 8 of 13 patients (61.5%) had angiographic restenosis (late loss=1.36±0.94 mm with a loss index=0.62±0.44). Conclusion—This first experience with QuaDS-QP2 stent implantation for in-stent restenosis revealed minimal intimal hyperplasia at the 6-month follow-up. However, the antiproliferative effect was not maintained at the 12-month follow-up, resulting in delayed occurrence of angiographic restenosis.

Low testosterone levels are associated with coronary artery disease in male patients with angina

Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58±4 years, range 43–72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8±6.5 and 13.5±5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0±1.5 vs 6.6±1.9 IU/l and 7.9±2.1 vs 4.4±1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84±0.45 vs 1.19±0.74 nmol/l, P<0.01 and 10.7±1.4 vs 13.3±3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=−0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.

Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test

OBJECTIVES Although different noninvasive tests have been proposed for detecting coronary artery disease (CAD) in patients with hypertension and chest pain symptoms, the relative performance of the available techniques has not been systematically assessed. BACKGROUND Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram. METHODS In 101 patients with hypertension, chest pain and positive exercise ECG, we performed stress/rest myocardial single photon emission computed tomography with 99mTc-MIBI, dipyridamole and dobutamine stress echocardiography and coronary angiography. All patients had normal global ventricular function and 57 had left ventricular hypertrophy. All were kept on ACE inhibitors during the study period. RESULTS No patients had significant side effects during perfusion scintigraphy. Dose-limiting side effects were observed in five patients with dipyridamole and in seven patients with dobutamine. Only 56% of study patients exhibited significant CAD. Sensitivity, specificity, accuracy, positive and negative predictive values were, respectively, 98%, 36%, 71%, 67% and 94% for perfusion scintigraphy, 61%, 91%, 74%, 90% and 64% for dipyridamole and 88%, 80%, 84%, 85% and 83% for dobutamine stress echocardiography. CONCLUSIONS This study shows that stress echo in patients with hypertension yields a satisfactory diagnostic accuracy for identifying significant epicardial CAD. Our results indicate that dobutamine might be superior to dipyridamole. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial CAD, possibly due to microvascular disease and not causing obvious wall motion abnormalities.

Direct coronary stenting without predilation

OBJECTIVES Coronary stenting is the primary therapeutic option for percutaneous treatment of many coronary lesions, after the risk of subacute stent thrombosis and bleeding complications has been reduced by improved antithrombotic regimens and high pressure stent expansion. BACKGROUND Direct stent implantation (without predilation) has been considered a promising new technique that may reduce the procedure time, radiation exposure time and cost. METHODS After having reviewed all cases of stent implantation from February to June 1998 (n = 585), 185 (32%) of these patients were retrospectively considered candidates for direct stent implantation without predilation, according to prespecified criteria (i.e., absence of severe coronary calcifications and/or tortuosity of the lesion or the segment proximal to the lesion). By operator preference, direct coronary stent implantation was actually attempted in 123 (21%) of the 585 patients (100 men, 60 +/- 10 years old) on 123 lesions. The impact of direct stenting in terms of cost, procedure time, radiation exposure time and amount of contrast dye used was assessed by comparing the two groups of patients who underwent single-vessel stenting without (n = 69) and with (n = 46) predilation. RESULTS Direct stenting was successful in 118 patients (96%). No acute or subacute complications occurred in these patients. Procedure time, radiation exposure time and cost were significantly lower in the group of patients who had single-vessel direct versus conventional stenting (45 +/- 31 vs. 64 +/- 46 min, 12 +/- 9 vs. 16 +/- 10 min and 1,305 +/- 363 vs. 2,210 +/- 803 Euro, respectively; p < 0.05 for all). CONCLUSIONS Direct stenting without predilation in selected lesions seems to be a safe and successful procedure that provides a way to contain cost and to shorten radiation exposure time.

Time course and determinants of left ventricular function recovery after primary angioplasty in patients with acute myocardial infarction.

OBJECTIVES We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion. METHODS Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients. RESULTS Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure. CONCLUSIONS Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Rotational atherectomy in resistant chronic total occlusions

Objectives: To assess the application of rotational atherectomy to improving the success rate of percutaneous recanalization of chronic total occlusion (CTO). Background: Although the inability to cross the occlusion with a guidewire is the reason for failure in the majority of cases, one of the most frustrating situations that may occur during a recanalization procedure is when a guidewire crosses successfully but it is impossible to advance any device over the wire through the occluded segment. Methods: From January 2006 to October 2009, 45/648 (7%) consecutive patients with CTO resistant to recanalization by conventional techniques were treated by high‐speed rotational atherectomy (Rotablator group). Results: All but two lesions were successfully crossed by Rotablator and eventually treated by stent implantation. As compared to the 603 CTO treated by conventional techniques (Conventional group), the 45 patients in the Rotablator group were older, more often female, active smokers, with chronic kidney disease and higher rate of previous surgical revascularization. The CTO in the Rotablator group had a longer duration. Peri‐procedural myocardial infarction was more frequent in the Rotablator group (35% vs. 22%; P = 0.044). Coronary perforation occurred only in three patients in the Conventional group and two of these patients needed urgent surgical intervention. No patient died from either group. Conclusions: The inability to cross a CTO with a balloon catheter occurs in approximately 7% of all CTOs that are successfully crossed with a guidewire. Rotational atherectomy is a safe and effective technique to overcome this frustrating situation.

Effect of atenolol on QT interval and dispersion in patients with syndrome X

Atenolol reduces QT dispersion and corrected QT interval in patients with syndrome X. This suggests that symptomatic improvement induced by atenolol in syndrome X patients may be partly related to reduction in abnormally augmented sympathetic tone.

Emergency stenting to treat neurological complications occurring after carotid endarterectomy

OBJECTIVES The purpose of this study was to assess the efficacy of emergency stent implantation for the treatment of perioperative stroke after carotid endarterectomy (CEA). BACKGROUND Carotid endarterectomy has been proven safe and effective in reducing the risk of stroke in symptomatic and asymptomatic patients with >60% carotid artery stenosis. However, perioperative stroke has been reported in 1.5% to 9% of CEA cases. The management of such a complication is challenging. Recently, percutaneous transluminal carotid angioplasty with stent deployment has emerged as a valuable and alternative strategy for the treatment of carotid artery disease. METHODS Between April 1998 and February 2000, 18 of the 995 patients (1.8%) who had CEA in our institution experienced perioperative major or minor neurological complications. Of these, 13 patients underwent emergency carotid angiogram and eventual stent implantation, whereas the remaining five had surgery re-exploration. RESULTS Carotid angiogram was performed within 20+/-10 min and revealed vessel flow-limiting dissection (five cases) or thrombosis (eight cases). Percutaneous transluminal carotid angioplasty with direct stenting (self-expandable stent) was performed in all 13 cases. Angiographic success was 100%. Complete remission of neurological symptoms occurred in 11 of the 13 patients treated by stent implantation and in one of the five patients treated by surgical re-exploration (p = 0.024). CONCLUSIONS Stent implantation seems to be a safe and effective strategy in the treatment of perioperative stroke complicating CEA, especially when carotid dissection represents the main anatomic problem.