Long-term results of a randomized controlled trial analyzing the role of systematic pre-operative coronary angiography before elective carotid endarterectomy in patients with asymptomatic coronary artery disease.

OBJECTIVES: To evaluate the potential benefit of systematic preoperative coronary-artery angiography followed by selective coronary-artery revascularization on the incidence of myocardial infarction (MI) in patients undergoing carotid endarterectomy (CEA) without a previous history of coronary artery disease (CAD). METHODS: We randomised 426 patients who were candidates for CEA, with no history of CAD, a normal electrocardiogram (ECG), and a normal cardiac ultrasound. In group A (n = 216) all patients underwent coronary angiography before CEA. In group B (n = 210) CEA was performed without coronary angiography. Patients were not blinded for relevant assessments during follow-up. Primary end-point was the occurrence of MI at 3.5 years. The secondary end-point was the overall survival rate. Median length of follow-up was 6.2 years. RESULTS: In group A, coronary angiography revealed significant coronary artery stenosis in 68 patients (31.5%). Among them, 66 underwent percutaneous Intervention (PCI) prior to CEA and 2 received combined CEA and coronary-artery bypass grafting (CABG). Postoperatively, no MI was observed in group A, whereas 6 MI occurred in group B, one of which was fatal (p = .01). During the study period, 3 MI occurred in group A (1.4%) and 33 were observed in group B (15.7%), 6 of which were fatal. The Cox model demonstrated a reduced risk of MI for patients in group A receiving coronary angiography (HR,.078; 95% CI, 0.024-0.256; p < .001). In addition, patients with diabetes and patients <70 years presented with an increased risk of MI. Survival analysis at 6 years by Kaplan-Meier estimates was 95.6 ± 3.2% in Group A and 89.7 ± 3.7% in group B (Log Rank = 6.54, p = .01). CONCLUSIONS: In asymptomatic coronary-artery patients, systematic coronary angiography prior to CEA followed by selective PCI or CABG significantly reduces the incidence of late MI and increases long-term survival. (ClinicalTrials.gov number, NCT02260453).

Systematic preoperative coronary angiography and stenting improves postoperative results of carotid endarterectomy in patients with asymptomatic coronary artery disease: a randomised controlled trial.

OBJECTIVE: To evaluate the usefulness of systematic coronary angiography followed, if needed, by coronary artery angioplasty (percutaneous coronary intervention (PCI)) on the incidence of cardiac ischaemic events after carotid endarterectomy (CEA) in patients without evidence of coronary artery disease (CAD). MATERIALS AND METHODS: From January 2005 to December 2008, 426 patients, candidates for CEA, with no history of CAD and with normal cardiac ultrasound and electrocardiography (ECG), were randomised into two groups. In group A (n=216) all the patients had coronary angiography performed before CEA. In group B, all the patients had CEA without previous coronary angiography. In group A, 66 patients presenting significant coronary artery lesions at angiography received PCI before CEA. They subsequently underwent surgery under aspirin (100 mg day(-1)) and clopidogrel (75 mg day(-1)). CEA was performed within a median delay of 4 days after PCI (range: 1-8 days). Risk factors, indications for CEA and surgical techniques were comparable in both groups (p>0.05). The primary combined endpoint of the study was the incidence of postoperative myocardial ischaemic events combined with the incidence of complications of coronary angiography. Secondary endpoints were death and stroke rates after CEA and incidence of cervical haematoma. RESULTS: Postoperative mortality was 0% in group A and 0.9% in group B (p=0.24). One postoperative stroke (0.5%) occurred in group A, and two (0.9%) in group B (p=0.62). No postoperative myocardial event was observed in group A, whereas nine ischaemic events were observed in group B, including one fatal myocardial infarction (p=0.01). Binary logistic regression analysis demonstrated that preoperative coronary angiography was the only independent variable that predicted the occurrence of postoperative coronary ischaemia after CEA. The odds ratio for coronary angiography (group A) indicated that when holding all other variables constant, a patient having preoperative coronary angiography before carotid surgery was 4 times less likely to have a cardiac ischaemic event after carotid surgery. No complications related to coronary angiography were observed and no cervical haematomas occurred in patients undergoing surgery under aspirin and clopidogrel in this study. CONCLUSIONS: Systematic preoperative coronary angiography, possibly followed by PCI, significantly reduces the incidence of postoperative myocardial events after CEA in patients without clinical evidence of CAD.

Glutathione sodium salt as a novel adjunctive treatment for acute myocardial infarction.

Timely recanalization of infarct related artery along with effective myocardial cell reperfusion represents a major challenge in the management of STEMI. The reperfusion of coronary arteries can induce further cardiomyocyte death by generating oxidative stress, which itself can mediate myocardial damage through a number of different mechanisms. Based on experimental and clinical studies, interventions to treat reperfusion injury by antioxidants were considered to be an appropriate therapeutic option. We emphasize the hypothesis that glutathione sodium salt, a physiologic antioxidant, may be of value when administered to STEMI patients both at an early stage of myocardial reperfusion by primary angioplasty and for up to three days after the procedure, in addition to standard treatment.

Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA.

OBJECTIVES: Isoprostanes, stable end-products of oxygen free radical mediated-lipid peroxidation, were measured in the coronary vessels during percutaneous transluminal coronary angioplasty (PTCA) to provide direct evidence for enhanced oxidative stress in a local milieu in vivo. BACKGROUND: Percutaneous transluminal coronary angioplasty is associated with complications such as myocardial stunning and accelerated restenosis, which at least in part are mediated by oxygen free radicals. Because isoprostanes are markers of oxidant stress and potent vasoactive compounds, the formation of which is not inhibited by aspirin treatment in vivo, it is possible that these mediators are increased locally during PTCA. METHODS: In 12 coronary artery disease patients who were given aspirin and ticlopidine, blood samples from coronary sinus were taken immediately before and immediately upon balloon deflation during PTCA. Isoprostane F2alpha-III, isoprostane F2alpha-VI, and TxB2 were quantified after extraction and chromatography using a stable dilution isotope gas chromatography/mass spectrometry assay. RESULTS: Coronary sinus and left main coronary artery levels of iPF2alpha-III and iPF2alpha-VI at baseline were (mean +/- SEM) 40 +/- 9 pg/ml and 115 +/- 10 pg/ml, respectively. The TxB2 levels were undetectable. Following PTCA, isoprostane levels markedly increased (mean +/- SEM): iPF2alpha-III, 125 +/- 12 pg/ml (p < 0.001); iPF2alpha-VI, 295 +/- 20 pg/ml (p < 0.001), whereas TxB2 levels remained undetectable. CONCLUSIONS: These results indicate that PTCA induces coronary sinus increase in F2-isoprostane formation, and they also provide direct evidence for enhanced oxidative stress in a local milieu in vivo. Thus, an increased F2-isoprostane formation could play a role in the pathogenesis of some PTCA-associated untoward events.

Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling.

OBJECTIVES: The purpose of this study was to determine whether contractile recovery induced by dobutamine in dysfunctioning viable myocardium supplied by nearly occluded vessels is related to an increase in blood flow in the absence of collaterals. BACKGROUND: Dobutamine is used to improve contractility in ventricular dysfunction during acute myocardial infarction. However, it is unclear whether a significant increase in regional blood flow may be involved in dobutamine effect. METHODS: Twenty patients with 5- to 10-day old anterior infarction and > or =90% left anterior descending coronary artery stenosis underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest echocardiography and scintigraphy were repeated >1 month after revascularization. Nine patients had collaterals to the infarcted territory (group A), and 11 did not (group B). RESULTS: Baseline wall motion score was similar in both groups (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p < 0.0001). Wall motion score improved significantly (p < 0.001) in group A both at dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas at dobutamine and postrevascularization studies a significant change (F[2,30] = 65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p < 0.0001) were present. Tracer uptake increased significantly in group A both at dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/-8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization (+8.8+/-7.2%, p < 0.001). CONCLUSIONS: The increase in contractility induced by low dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase in blood flow.

Handgrip increases endothelin-1 secretion in normotensive young male offspring of hypertensive parents.

OBJECTIVES: We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents. BACKGROUND: It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension. METHODS: Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery. RESULTS: Group A had higher norepinephrine levels than group B throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p < 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p < 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square=7.59, p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not. CONCLUSIONS: The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.

Evaluation of hand circulation with CardioWaves photoplethysmograph device during Allen test in healthy volunteers.

OBJECTIVE: Radial artery occlusion is a potential complication of transradial procedures and its occurrence ranges from 0.8 to 30%. It is virtually always asymptomatic but the functional and sensorial consequences of a long acting hand hypoperfusion could go underestimated. CardioWaves is a novel photoplethysmograh device that allows us to detect the pulse wave amplitude of the blood flowing to the hand. Our objective was to assess in normal subjects the hand blood flow supplied by radial arteries and ulnopalmar arches, respectively, by using CardioWaves device during modified Allen's test (MAT). PATIENTS AND METHODS: MAT was performed on both hands of 60 normal subjects, age ranging 21 to 66 years, without any cardiovascular factor risk. RESULTS: Photoplethysmograh and MAT showed a high positive linear correlation (r=0.93). Despite that, MAT tends to give a higher reading by between 1.05 and 1.6 sec. 11 of 120 readings (9%) by CardioWaves showed values of radial/ulnar pulse amplitude ratio more than mean + 1 SD, suggesting a significant decrease in ulnopalmar arterial circulation when radial blood flow supply would ceased. CONCLUSIONS: The CardioWaves device allows us an accurate reading of the flow because of its independency from respiratory changes. Furthemore, the evaluation of radial and ulnar pulse wave amplitude and the ratio between them would reveal an insufficient blood flow supply by the ulnar artery irrespective of the MAT results. We suggest that their assessment before performing coronary angiography and interventions may reduce potential complication of transradial access.

Isometric handgrip exercise increases endothelin-1 plasma levels in patients with chronic congestive heart failure.

This study demonstrated an immediate and short-lasting endothelin-1 release in the circulation of patients with severe chronic congestive heart failure during isometric handgrip exercise, but not in normal subjects. Our data suggest that endothelin-1 levels may increase transiently during daily physical activity, thus contributing to progressive deterioration of left ventricular function.

Enoximone coupled to very low dose dobutamine echocardiography detects myocardial viability in akinetic and dyskinetic post-myocardial infarcted areas.

Dobutamine and enoximone stimulate independently inotropic reserve by increasing intracellular cyclic adenosine monophosphate. The potential of enoximone (0.75 mg/kg body weight over 10 minutes) followed by very low dose (2.5 microg/kg/min) dobutamine echocardiography to predict recovery of ventricular function in akinetic and dyskinetic postinfarcted areas was studied. We enrolled 22 patients with previous Q-wave myocardial infarction and regional wall motion abnormalities related to left anterior descending arterial disease, left ventricular ejection fraction <40%, and all scheduled for myocardial revascularization. A 10 microg/kg/min dobutamine test was performed 48 hours before the study protocol. Test images obtained at peak of pharmacodynamic effects were compared with those obtained at 4 months after myocardial revascularization. We used a 16-segment ventricular model and a 5-grade scoring system. Resting regional myocardial dysfunction graded > or =2 was present in 267 of 352 segments evaluated. Contractile reserve (decrease in resting wall motion score > or =2 grades) at peak effect of enoximone infusion was present in 34 of 112 severely hypokinetic, 42 of 117 akinetic, and 14 of 38 dyskinetic segments. The inotropic reserve evaluated after very low dose dobutamine was observed in 34 of 112 severely hypokinetic, 49 of 117 akinetic, and 20 of 38 dyskinetic segments. After revascularization, recovery of function was observed in 31 of 112 severely hypokinetic, 49 of 117 akinetic, and 21 of 38 dyskinetic segments. Overall, there was a significant correlation between absolute score changes of segments which were abnormal at baseline (n = 267) to enoximone peak effects (r = 0.49, p <0.001) to predict absolute changes after revascularization; after dobutamine there was progress toward identity (r = 0.62, p <0.001) and the difference was significant among correlation slopes of dobutamine alone, enoximone alone, and enoximone plus very low dose dobutamine echocardiograophy (0.45+/-0.04, 0.51+/-0.04, and 0.63+/-0.04, respectively, F = 5.25, p = 0.005). Therefore, enoximone followed by very low dose dobutamine may assess myocardial viability of postinfarcted akinetic and dyskinetic areas. This test may be useful when evaluating patients with more severe cardiac failure and/or life-threatening arrhythmias.

Acute hemodynamic effects of acebutolol and propranolol.

The acute hemodynamic effects of intravenous acebutolol, 50 mg, and propranolol, 10 mg, were evaluated in 12 patients undergoing diagnostic cardiac catheterization. Each patient received acebutolol or propranolol according to a list of randomization. Both acebutolol and propranolol depressed left ventricular function. There was a significant increase in left ventricular end-diastolic pressure at rest and after isometric exercise, with a concomitant decrease in cardiac index. Systemic vascular resistance was increased by both drugs. The increment after patients received acebutolol was not statistically significant; however, with propranolol it was statistically significant. The overall hemodynamic effects of acebutolol and propranolol are similar, but a quantitative difference exists in their effect on systemic vascular resistance. Acebutolol, a cardioselective agent, produces less of a peripheral vascular beta 2-blockade than does propranolol.

Acquired coronary-to-left ventricle fistula: evidence by myocardial contrast echocardiography.

The case report subject is a patient with an old anteroseptal myocardial infarction and postinfarction angina who developed, over the years, a small left coronary-to-left ventricle fistula. The first coronary angiogram, performed 4 months after the infarction, was negative for coronary fistula. The diagnosis was made 3 years later, at repeat cardiac catheterization with myocardial contrast echocardiography. Left and right coronary injections of 0.2 cc of sonicated 5% human albumin microbubbles generated a bright cloud of contrast entering the left ventricular cavity at the level of the distal third of the interventricular septum. Conversely, cineangiography failed to show on-line the fistulous communication that was evident only after careful cineangiographic reviewing. This case demonstrates the high efficacy of myocardial contrast echocardiography in identifying very small coronary fistulae.

Angina and normal epicardial coronary arteries: radionuclide features and pathophysiological implications at long-term follow-up.

BACKGROUND: The aim of this study was to identify specific characteristics associated with modifications of symptoms and to evaluate the presence of a pathophysiological link between radionuclide abnormalities and delayed run-off of coronary contrast dye in patients with angina and normal coronary arteries. METHODS: We followed up 53 patients (21 men and 32 women, mean age: 52 +/- 10 years) with angina and angiographically normal epicardial coronary arteries, 21 of whom (40%) displayed a pattern of slow contrast dye run-off from coronary vessels, on visual assessment using a semiquantitative empirical score. Exercise tests showed ECG abnormalities in 29 patients (55%). RESULTS: All patients were alive 92 +/- 44 months after catheterization (140 +/- 79 months after beginning of symptoms). However, 30 patients (57%), who reported worsening or no change of symptoms, presented with a non-significant higher prevalence of conduction abnormalities at rest ECG (27 versus 17%), pathological exercise tests (57 versus 52%), and delayed run-off (47 versus 30%). Regional left ventricular function and perfusion were then simultaneously assessed at rest and peak exercise with 99mTc-sestamibi. Exercise-induced radionuclide abnormalities were detected in 27 patients (51%), who also presented with a non-significant higher prevalence of pathological exercise tests (63 versus 43%) and no improvement of symptoms (63 versus 46%). However, exercise-induced functional and perfusional abnormalities were simultaneously present in 29 out of 42 (69%) coronary territories supplied by vessels with delayed run-off, versus 21 out of 117 (17%) normal territories (P = 0.00032). CONCLUSIONS: Despite a good prognosis, some patients with angina and normal coronary arteries presented no improvement of symptoms at follow-up, and had functional and perfusional abnormalities in coronary territories supplied by vessels showing delayed contrast dye run-off.

Undetected acute aortic dissection in a patient referred for primary coronary angioplasty: a successful treatment of perioperative bleeding after abciximab administration.

The authors describe a case of an acute aortic dissection in a Japanese woman with long-lasting hypertension, who was referred to our cath lab for primary percutaneous coronary intervention because of an ECG feature of acute inferior myocardial infarction and systemic hypotension. A successful treatment of perioperative bleeding followed a missed diagnosis in the early stages and abciximab administration.

Clinical significance of small left-to-right shunts after percutaneous mitral valvuloplasty.

Left-to-right shunt after percutaneous mitral valvuloplasty was evaluated by contrast echocardiography in 29 patients at 24 hours and at 1, 3, 6, and 9 months after the procedure. The patients were divided into two groups: in group A (13 patients) the double-balloon technique was used; in group B (16 patients) the Inoue single-balloon technique was used. The two groups were comparable in terms of age, gender, and mitral valve area before and after percutaneous mitral valvuloplasty. A left-to-right shunt was detected in all patients 24 hours after the procedure. At 1 month follow-up the shunt was present in 12 patients of group A (92%) and in 13 of group B (81%) with a statistically significant difference (p < 0.001). At 3 months the values were 7 (54%) in group A and 6 (37.5%) in group B (p < 0.05); at 6 months the values were 3 (23%) in group A and 3 (19%) in group B (NS). At 9 months a left-to-right shunt was no longer detectable in any of the patients in either group. The disappearance of the shunt could be related to a healing process of the atrial septal injury that occurs within a few months after percutaneous mitral valvuloplasty. This process seems to be more rapid in group B patients, probably because of the smaller lesion that is produced in the atrial septum by the passage of the Inoue balloon.

Hemodynamic and clinical effects of captopril in patients with severe congestive heart failure.

In a group of 10 patients (9 male, 1 female, aged 16 to 56, mean 43 years) with severe congestive heart failure (CHF), due to ischemic heart disease (8 cases) or dilatative cardiomyopathy (2 cases), the acute hemodynamic response to captopril (CPT) (90 min after 50 mg po) was evaluated. CPT was then given starting with 15 mg q 8 hr, gradually increased within 2 or 3 days to 50 or 75 mg q 8 hr. A hemodynamic re-evaluation was performed after 20 days, and, in 5 patients, after 1 year of CPT treatment. The clinical follow-up done every 3 months in the outpatient clinic. CPT acutely produced a decrease in mean pulmonary wedge pressure: 23.8 +/- 8.9 to 18.6 +/- 8.6 mmHg, p less than 0.01, and an increase in cardiac index: 2.43 +/- 0.73 to 2.91 +/- 0.85 l/min/m2, p less than 0.01; systemic and pulmonary resistances decreased significantly, with no significant changes in heart rate and in mean brachial artery pressure. This favourable hemodynamic response persisted after 20 days of CPT treatment. In the group of 5 patients, who underwent a third hemodynamic evaluation, no statistically significant differences were demonstrated in respect to the previous control values. All patients on chronic CPT treatment experienced a gradual clinical improvement, reaching a steady state after 2 to 3 weeks; the surviving patients remained stable in the improved functional class for at least 6 months. The mortality rate was 30% in the first year, increasing to 50% in the second and to 60% in the third year of treatment. After a mean follow-up 35.7 months (range 33 to 39) the 4 surviving patients remained in the same functional class as after the first year for therapy. In our CHF patients CPT improved the quality of life, with the best clinical and hemodynamic results the first few months of treatment; life expectancy probably was not affected.

Permanent mechanical catheter ablation of an accessory pathway in a child.

Permanent mechanical ablation of an accessory atrioventricular pathway was observed in an infant during intracavitary electrophysiological mapping. The persistent lack of preexcitation was confirmed during a 15-month follow-up period.

Nomogram for calculation of stenotic cardiac valve areas from cardiac output and mean transvalvular gradient.

In 15 patients (group 1) with isolated mitral stenosis and in 14 patients (group 2) with isolated aortic stenosis the stenotic valve areas were calculated according to: A) Gorlin's formula; B) Hakki's simplified formula, using mean mitral gradient by planimetry or peak-to-peak aortic gradient; C) the three-point simplified formula, using mean gradient calculated by the three-point method for both mitral and aortic valve. The three-point method is definitely easier to use than planimetry. The values (mean +/- SD) of mitral valve areas in group 1 patients were, respectively: 1.56 +/- 0.63 cm2; 1.56 +/- 0.55; 1.51 +/- 0.53. The values of aortic valve areas in group 2 patients were: 0.91 +/- 0.63; 0.77 +/- 0.41; 0.88 +/- 0.52. An excellent correlation was shown between the valve area calculated by Gorlin's formula and both Hakki's simplified formula and the three-point simplified formula. For aortic valve area the correlation is even better if the mean gradient by the three-point method is used instead of the peak-to-peak gradient. On the basis of the simplified formula, a nomogram was constructed which allows an immediate calculation of valve areas from cardiac output and transvalvular gradient.