Oxidative stress changes after stent implantation: a randomized comparative study of sirolimus-eluting and bare metal stents.

BACKGROUND: Although oxidative stress plays an important role in the pathophysiology of restenosis, its role following the implantation of sirolimus-eluting stents (SES) is unknown. METHODS: We examined the relation between total peroxides (TP), a marker of oxidative stress, and in-stent late luminal loss over a 6-month follow-up in patients with stable coronary artery disease and compared the results from SES with those from bare metal stents (BMS). We enrolled 75 consecutive patients, who underwent successful PCI and were randomly allocated to SES (n=37) or BMS (n=38). Blood samples were taken 24 h before, at 24 h, 48 h and 1 month after angioplasty; levels of TP were determined on each occasion. Follow-up coronary angiography was performed 6-8 months later. RESULTS: TP levels in the BMS group were significantly higher at 24 h and 48 h compared to baseline (p=0.006 for both). At one month there was a significant decline from the 48 h levels (p=0.029) to levels slightly, but not significantly higher than baseline. In contrast, in SES TP levels showed no significant changes during the first 48 h, while they declined to levels somewhat lower than baseline at 30 days. A significant correlation was found between TP changes and in-stent late luminal loss at 6 months in both groups. CONCLUSION: Our study showed that patients with stable coronary artery disease who received SES have a different behavior of oxidative stress after stenting compared with BMS, and this could contribute to the difference in restenosis rate between these 2 types of stents.

Isolated atrial microvascular dysfunction in patients with lone recurrent atrial fibrillation.

OBJECTIVES: The purpose of this study was to assess atrial myocardial perfusion in patients with lone recurrent atrial fibrillation (LRAF). BACKGROUND: Although acute atrial ischemia has been implicated in the pathogenesis of atrial fibrillation, there are few data concerning human atrial myocardial perfusion and none for patients with LRAF. METHODS: Sixteen patients with LRAF and 15 control subjects with suitable coronary anatomy underwent time-averaged peak coronary blood flow velocity (APV) measurements (cm/s), using a Doppler guidewire in the proximal left circumflex coronary artery (LCx) and in the left atrial circumflex branch (LACB), at baseline (b) and after adenosine administration to achieve maximal hyperemia (h). Coronary flow reserve was defined as h-APV/b-APV. RESULTS: Although there were no statistically significant differences in b-APV between patients with LRAF and control subjects or between the LACB and LCx, there were significant group (p = 0.002), artery (p = 0.001), and interaction (p < 0.001) effects at maximal hyperemia. In patients with LRAF, the h-APV and coronary flow reserve of the LACB (30.4 +/- 9.5 cm/s and 2.2 +/- 0.4, respectively) were significantly lower than in the LACB of the control subjects (45.8 +/- 12.8 cm/s [p < 0.001] and 2.9 +/- 0.5 [p = 0.001], respectively) or in the patients' LCx (43.0 +/- 10.9 cm/s [p = 0.001] and 3.1 +/- 0.6 [p < 0.001], respectively). CONCLUSIONS: This study confirms for the first time isolated atrial myocardial perfusion abnormalities in patients with LRAF and coronary flow reserve impairment, indicating that microvascular dysfunction is a pathophysiological substrate associated with this arrhythmia.

Vascular endothelial growth factor protein levels and gene expression in peripheral monocytes after stenting: a randomized comparative study of sirolimus: eluting and bare metal stents.

AIMS: Although previous studies have indicated that vascular endothelial growth factor (VEGF) plays an important role in the vascular-healing process after stent implantation, its effect on in-stent restenosis is unclear. We assessed VEGF serum protein levels and gene expression in peripheral monocytes in relation to in-stent restenosis after implantation of sirolimus-eluting (SES) and bare metal stents (BMS) in a non-blinded, randomized study. METHODS AND RESULTS: Forty-two patients (28 men, age 62 +/- 11 years) with stable angina, who underwent elective single-vessel percutaneous coronary intervention, were randomized to SES (n = 21) or BMS (n = 21) implantation. VEGF protein levels in the BMS group showed an increasing trend (P = 0.083), whereas in the SES group they decreased significantly (P = 0.002). BMS induced up-regulation of VEGF mRNA levels, whereas for SES down-regulation was observed. There was no correlation between serum levels and late luminal loss. A significant correlation was found between VEGF gene expression and late luminal loss in both groups (BMS: r = 0.98, P < 0.001; SES: r = 0.65, P = 0.002). CONCLUSION: SES, in comparison with BMS, results in lower VEGF protein levels and gene expression in peripheral monocytes. The latter shows a positive relationship with in-stent late-luminal loss, suggesting an essential role in the reduced in-stent restenosis seen in SES.

Acute effect of esmolol intravenously on coronary microcirculation in patients with idiopathic dilated cardiomyopathy.

Although coronary flow reserve (CFR) impairment was correlated with the prognosis of patients with idiopathic dilated cardiomyopathy (IDC) and microvascular ischemia was implicated in the progress of the disease, little is known about the effect of the established therapy with beta blockers on coronary microcirculation. The purpose of this study was to assess the effect of beta(1) blockade on coronary blood flow and CFR in patients with IDC. Fourteen patients with IDC and 10 control subjects underwent time-averaged peak coronary flow velocity (APCFV) measurements (centimeters per second) in the proximal left anterior descending coronary artery at baseline and at maximal hyperemia before and after beta(1) blockade with intravenous esmolol. CFR was defined as APCFV at maximal hyperemia/APCFV at baseline. Although there were no significant differences in APCFV at baseline between patients with IDC and controls, patients with IDC had significantly lower APCFV at maximal hyperemia than controls (54.2 +/- 12.0 vs 75.1 +/- 18.6, p <0.05) and decreased CFR (2.39 +/- 0.38 vs 3.50 +/- 0.54, respectively, p <0.05). After beta(1) blockade, a significant decrease in APCFV at baseline (19.5 +/- 3.7 vs 22.9 +/- 5.0, p <0.05) and enhancement of APCFV at maximal hyperemia (59.5 +/- 13.3 vs 54.2 +/- 12.0, p <0.05) were observed in patients with IDC, but not in control subjects, leading to significant improvement in CFR (3.06 +/- 0.40 vs 2.39 +/- 0.38, p <0.05). In conclusion, patients with IDC had alterations in coronary blood flow and decreased CFR that improved after beta(1) blockade. These alterations in microvascular function, which are partially reversed by beta blockade, may be 1 of the underlying mechanisms that contribute to the improved prognosis of patients with IDC under such therapy.

Endothelial cell function during atrial fibrillation and after restoration of sinus rhythm.

Beat-to-beat variation in blood flow dynamics during atrial fibrillation (AF) has been associated with evidence of endothelial dysfunction. The aim of the present work is to confirm endothelial dysfunction in patients with AF and test the hypothesis that endothelial dysfunction is reversible upon restoration of normal sinus rhythm. Endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (nitroglycerin-mediated dilation [NMD]) vasodilator function of the brachial artery were measured using high-resolution ultrasound in 46 patients with persistent AF who were scheduled for internal electrical cardioversion and in 25 control subjects. In patients who remained in sinus rhythm after cardioversion, these measurements were repeated after 24 hours (n = 32) and 1 month (n = 19). Compared with control subjects, patients (n = 32) showed lower FMD during AF (8.1 +/- 3.6% vs 12.2 +/- 3.2%, respectively, p <0.001) and similar NMD (17.0 +/- 3.5% vs 15.9 +/- 3.1%, respectively, p = 0.21). In 19 patients who remained in sinus rhythm, FMD increased at both 24 hours (8.0 +/- 3.9% vs 10.6 +/- 4.6%, p = 0.015) and 1 month (8.0 +/- 3.9% vs 13.6 +/- 5.3%, p <0.001). In contrast, NMD was not significantly altered at 24 hours or 1 month after sinus rhythm restoration (17.1 +/- 3.9% vs 17.2 +/- 4.0% vs 16.9 +/- 4.1%). In conclusion, AF is associated with impairment in endothelial function that improves after sinus rhythm restoration.

Combined use of aspiration catheter and distal embolisation protection device to facilitate angioplasty of a totally occluded saphenous vein graft.

Angioplasty of totally occluded saphenous vein grafts is a very challenging procedure and the likelihood of distal embolisation and no-reflow is much higher than in any conventional angioplasty. The use of thrombus aspiration and distal protection devices, although not well studied in a large number of patients, has been shown to be quite effective in preventing such complications. In this case we report our satisfactory experience from the combined use of a novel aspiration catheter and a distal protection device for the treatment of a totally occluded saphenous vein graft.

Reduced systemic inflammatory response to implantation of sirolimus-eluting stents in patients with stable coronary artery disease.

Stent implantation causes significant injury to the vascular wall, resulting in inflammatory activation. Although sirolimus-eluting stents (SES) have anti-inflammatory properties, their effect on periprocedural systemic inflammatory response has not been sufficiently investigated. Eighty-one patients with stable coronary artery disease involving severe stenosis of one major epicardial coronary artery underwent coronary angioplasty with stent implantation and randomly received either SES or bare metal stents (BMS). Blood samples were taken 24h before, at 24h, 48 h and 1 month after the angioplasty and levels of high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and monocyte chemoattractant protein-1 (MCP-1) were determined. HsCRP after BMS implantation increased over 24h (p<0.001) and then remained steady, as did IL-6 and IL-1 beta similarly. In contrast, their levels in SES patients decreased to below baseline by the end of the month. MCP-1 levels increased by the end of 1 month (p<0.001) in the BMS group, whereas in SES they steadily decreased, becoming significantly lower than baseline from 48 h (p=0.015). In conclusion, patients with SES exhibit an attenuation of the postprocedural systemic inflammatory activation during a 1-month follow-up after stent implantation. This might partially explain the reduced restenosis rate associated with SES.

Effect of inhaled salbutamol on coronary circulation in humans.

In 12 patients we assessed the effect of inhaled salbutamol on the coronary circulation. According to our results, large doses of salbutamol increase coronary flow, but not in proportion to the needs of the myocardium (as documented by the increase in coronary oxygen extraction), and decrease coronary flow reserve. These effects may have deleterious consequences in patients with coronary artery disease, causing or worsening myocardial ischemia.

Atrial fibrillation is associated with increased neurohumoral activation and reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy.

OBJECTIVES: To assess atrial fibrillation (AF) associated differences in proinflammatory cytokines, natriuretic peptide levels and exercise capacity in patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy (NIDC). METHODS: We studied 147 NIDC patients, mean age 58.3+/-12.5 years, left ventricular (LV) ejection fraction 27.8+/-10.9% and NYHA class II-III. Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6, tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional class was assessed by cardiopulmonary exercise test. RESULTS: Forty patients (27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF duration compared to patients in sinus rhythm (SR). AF was associated with increased levels of IL-6 (p=0.001), TNF-a (p=0.002), sTNFRI (p=0.023), NT-ANP (p<0.001) and NT-BNP (p=0.003), decreased exercise duration (p<0.001) and slightly reduced maximal oxygen consumption at peak exercise (p=0.07) compared to SR patients. No significant differences in cytokine and natriuretic peptide levels or exercise tolerance were noted when patients in AF were compared to the subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed that NT-ANP (p=0.003) and IL-6 (p=0.006) plasma levels were independently associated with the presence of AF in our patient population. CONCLUSION: AF is associated with increased inflammatory state, natriuretic peptide levels and reduced exercise capacity in patients with HF secondary to NIDC. These findings suggest that the presence of AF in HF represents a more advanced stage of the syndrome.

Successful thrombus removal during angioplasty in a patient with acute myocardial infarction using a new aspiration catheter.

We describe the case of a male patient, aged 62 years, with acute myocardial infarction, who underwent primary angioplasty using a new thrombus aspiration catheter in conjunction with the conventional technique. This catheter is easier to use than similar devices available to date and is extremely effective in the removal of large intracoronary thrombi, thus providing protection against distal embolism during angioplasty procedures.

Acute myocardial infarction in a patient with normal coronary arteries after an allergic reaction.

The case is described of a man aged 51 years who, one hour after a coronary angiographic examination that showed coronary arteries without lesions, suffered an acute inferior myocardial infarction as the result of an acute allergic reaction, probably to the iodinated contrast agent that was used. Acute myocardial infarction following an allergy is an extremely rare clinical entity that, according to existing data, is due to the local release of vasoconstrictive substances as a result of the allergic reaction.

Regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Although IDCM has been associated with alterations in coronary blood flow and contractile reserve, little is known about their regional distribution and correlation. METHODS: Fourteen patients with IDCM and 11 control subjects underwent coronary flow velocity (APV) measurements in the left anterior descending (LAD), left circumflex (LCx), and right coronary (RCA) arteries at baseline (b) and at maximal hyperemia (h). Coronary flow reserve (CFR) was defined as h-APV/b-APV. Wall thickening was assessed in 16 segments (7 assigned to LAD, 5 to LCx, and 4 to RCA) both at rest and under peak stress during low-dose dobutamine echocardiography. Regional contractile reserve was defined as the percentage difference in wall motion score index between rest and stress in each vascular territory. RESULTS: Although there were no significant differences in b-APV, patients with IDCM had significantly lower h-APV than controls in all three vascular territories and reduced CFR (LAD: 2.79 +/- 0.43 vs. 3.48 +/- 0.51, p < 0.05; LCx: 2.71 +/- 0.39 vs. 3.36 +/- 0.65, p < 0.05; and RCA: 3.43 +/- 0.55 vs. 4.02 +/- 0.73, p < 0.05). There was also a significant correlation between CFR and the corresponding contractile reserve in the vascular territory of the LAD (r = 0.75, p = 0.002) and the LCx (r = 0.64, p = 0.014). CONCLUSIONS: Patients with IDCM have alterations in regional coronary flow and reduced CFR. Furthermore, the correlation between regional CFR and the corresponding contractile reserve indicates that microvascular dysfunction may have a pathophysiologic role in the evolution of the disease.

Phasic coronary blood flow velocity pattern and flow reserve in the atrium: regulation of left atrial myocardial perfusion.

OBJECTIVES: The purpose of this study was to assess rest and stress atrial coronary blood flow (CBF) velocity and flow reserve. BACKGROUND: Because of the limitations of the methods used until now for assessing myocardial perfusion (MP) in the small mass of atrial tissue, data are lacking for human atrial MP. METHODS: Seventeen patients with suitable coronary anatomy underwent CBF velocity measurements with the use of a Doppler guide wire in the proximal left circumflex coronary artery (LCx) and left atrial circumflex branch (LACB), at baseline and after adenosine administration. All measurements were performed at resting heart rate and at 100 and 120 beats/min. RESULTS: Coronary blood flow velocity in the LACB showed a predominant systolic pattern in contrast to the diastolic pattern of the LCx. There was a disproportionate increase in baseline time-averaged peak coronary flow velocity (cm/s) between the LACB and LCx during the two levels of pacing-induced stress (16.8 +/- 5.5 vs. 16.2 +/- 5.1 at rest; 22.9 +/- 7.9 vs. 18.4 +/- 5.2 at 100 beats/min; and 27.1 +/- 8.0 vs. 20.4 +/- 5.1 at 120 beats/min; significant interaction, p < 0.001), but there were no significant differences in coronary flow reserve (CFR). CONCLUSIONS: Coronary blood flow in the left atrium is out of phase with that in the ventricular myocardium, showing a predominant systolic pattern. Although atrial and ventricular CFR show no significant differences at rest and with two levels of stress, the disproportionate increase in atrial blood flow velocity during stress indicates a peculiarity of atrial perfusion regulation.

Plasma Levels of Nitrites/Nitrates in Patients with Chronic Atrial Fibrillation are Increased after Electrical Restoration of Sinus Rhythm.

INTRODUCTION: Patients with persistent atrial fibrillation (AF) have hemodynamic changes, which impair endothelial cell function resulting in decreased nitric oxide (NO) production. The aim of this work was to assess endothelial function in AF patients before and at various time points after cardioversion. METHODS: Forty-two patients with AF and 21 normal and age-adjusted healthy controls were studied. Nitrites and nitrates (NO(x)) and von Willebrand factor (vWf) concentrations were measured on blood samples taken just before cardioversion and over a 30 day period after the procedure. RESULTS: Plasma levels of NO(x) in AF were significantly lower compared to healthy controls (p < 0.001), but after cardioversion gradually increased to approach to those of the healthy controls by the end of the first month of sustained sinus rhythm (p = 0.004). Interestingly plasma levels of NO(x) were negatively correlated to left atrial volume measured by ultrasonography (r = -0.34, p < 0.05). Plasma levels of vWf in AF patients were significantly higher compared to the healthy controls (p < 0.01) but with sustained sinus rhythm decreased (p = 0.02). CONCLUSION: The parallel normalization of the NO(x) titers and vWf levels suggests that vascular endothelial function improves after 30 days of normal sinus rhythm.

Electrocardiographic appearance of old myocardial infarction in paced patients.

This study evaluated the possibility of diagnosing chronic myocardial infarction in the presence of the pacing electrocardiogram. Forty-five patients with known myocardial infarction (anterior 23, inferior 22) and 26 healthy controls were studied. After coronary angiography, pacing was applied from the right ventricular apex, and the sensitivity, specificity, and average diagnostic accuracy of five criteria on the paced electrocardiogram were assessed: (1) Notching 0.04 second in duration in the ascending limb of the S wave of leads V3, V4, or V5 (Cabrera's sign); (2) Notching of the upstroke of the R wave in leads I, aVL, or V6 (Chapman's sign); (3) Q waves > 0.03 second in duration in leads I, aVL, or V6; (4) Notching of the first 0.04 second of the QRS complex in leads II, III, and aVF; (5) Q wave > 0.03 second in duration in leads II, III, and aVF. The most sensitive criteria, for anterior and inferior myocardial infarctions were Cabrera's and Chapman's (91.1 and 86.6%, respectively). All criteria had low specificity (range 42.3-69.2%). The combination of Cabrera's and Chapman's sign decreased the sensitivity to 77.7%, but increased specificity to 82.2%. The sensitivity and specificity of all the criteria were independent of the myocardial infarction site. In paced patients, the application of electrocardiographic criteria, and especially the combination of Cabrera and Chapman, provides useful clinical information in recognizing prior myocardial infarction but not in assigning the specific infarct site.

Value of Doppler index combining systolic and diastolic myocardial performance in predicting cardiopulmonary exercise capacity in patients with congestive heart failure: effects of dobutamine.

STUDY OBJECTIVE: Doppler-derived myocardial performance index (MPI), a measure of combined systolic and diastolic myocardial performance, was assessed at rest and after low-dose dobutamine administration in patients with idiopathic or ischemic dilated cardiomyopathy. MPI also was correlated with other conventional echocardiographic indexes of left ventricular (LV) function, and its ability to assess cardiopulmonary exercise capacity in those patients was investigated. SETTINGS: A tertiary-care, university heart failure clinic. PATIENTS: Forty-two consecutive patients (27 men; mean [+/- SD] age, 57 +/- 10 years) with heart failure (New York Heart Association [NYHA] class, II to IV) who had received echocardiographic diagnoses of dilated cardiomyopathy. Coronary angiography distinguished the cause of dilated cardiomyopathy. INTERVENTIONS: Low-dose IV dobutamine was infused after patients underwent a baseline echocardiographic study. All patients also underwent a cardiopulmonary exercise test using a modified Naughton protocol. RESULTS: Advanced NYHA class and restrictive LV filling pattern were associated with higher index values. A negative correlation was found between MPI and LV stroke volume, cardiac output, early filling/late filling velocity ratio, and late LV filling velocity, as well as oxygen uptake at peak exercise (r = -0.550; p < 0.001) and at the anaerobic threshold (r = -0.490; p = 0.002). Dobutamine administration produced an improvement in MPI, reducing its value and decreasing the isovolumic relaxation and contraction times. Stepwise regression analysis revealed that the rest index and the late LV filling velocity were the only independent predictors of cardiopulmonary exercise capacity. CONCLUSION: MPI correlates inversely with LV performance, reflects disease severity, and is a useful complimentary variable in the assessment of cardiopulmonary exercise performance in patients with heart failure.