Alessandro Loaldi

Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle.

BackgroundAt any given perfusion pressure, coronary reserve is expressed by the difference between autoregulated and maximally vasodilated flow. In hypertension the raised coronary resistance reduces the steepness of the pressure-flow relationship at maximal vasodilatation. In the presence of cardiac hypertrophy the line of autoregulated flow becomes higher. For these reasons coronary reserve is reduced and the point at which baseline flow approaches the maximal achievable flow might be shifted to a higher perfusion pressure. Thus, any reduction below this elevated and critical value of pressure would lower the coronary flow. Methods and ResultsThe investigated patients were normotensive (controls, nine) and hypertensive with normal (group I, seven) or augmented LV mass index because of concentric LV hypertrophy (group II, eight). All had effort-induced angina and angiographically normal left epicardial branches. Flow in the great cardiac vein was measured by thermodilution in the baseline and during stepwise (5 mm Hg every 5 minutes) decrease of the coronary perfusion pressure with a titrated nitroprusside i.v. infusion; perfusion pressures of 60 mm Hg in the controls and 70 mm Hg in the hypertensives were taken as end points. Baseline flow averaged 102 ml/min in normotensives, 104 ml/min in hypertensive group I and 148 ml/min in hypertensive group II. At the end points flow was similar to baseline in the controls and group I. In group II coronary flow started to decline and myocardial 02 extraction started to slightly but significantly rise at perfusion pressures of 90-80 mm Hg; at the end point flow was reduced by 26% (p<0.01 from baseline). The perfusion patterns did not seem to be related to the changes in tension-time index and heart rate. ConclusionsThe association of high blood pressure (reduced ability of the coronary arterioles to dilate) and hypertrophy of the myocardium (augmented baseline coronary flow) may shift the point of exhaustion of coronary reserve to a higher perfusion pressure and make the myocardium vulnerable to treatment-induced relative hypertension. (Circulation 1991;83:845–853)

Microembolization during carotid artery stenting in patients with high-risk, lipid-rich plaque: A randomized trial of proximal versus distal cerebral protection

OBJECTIVES The goal of this study was to compare the rate of cerebral microembolization during carotid artery stenting (CAS) with proximal versus distal cerebral protection in patients with high-risk, lipid-rich plaque. BACKGROUND Cerebral protection with filters partially reduces the cerebral embolization rate during CAS. Proximal protection has been introduced to further decrease embolization risk. METHODS Fifty-three consecutive patients with carotid artery stenosis and lipid-rich plaque were randomized to undergo CAS with proximal protection (MO.MA system, n = 26) or distal protection with a filter (FilterWire EZ, n = 27). Microembolic signals (MES) were assessed by using transcranial Doppler during: 1) lesion wiring; 2) pre-dilation; 3) stent crossing; 4) stent deployment; 5) stent dilation; and 6) device retrieval/deflation. Diffusion-weighted magnetic resonance imaging was conducted before CAS, after 48 h, and after 30 days. RESULTS Patients in the MO.MA group had higher percentage diameter stenosis (89 ± 6% vs. 86 ± 5%, p = 0.027) and rate of ulcerated plaque (35% vs. 7.4%; p = 0.019). Compared with use of the FilterWire EZ, MO.MA significantly reduced mean MES counts (p < 0.0001) during lesion crossing (mean 18 [interquartile range (IQR): 11 to 30] vs. 2 [IQR: 0 to 4]), stent crossing (23 [IQR: 11 to 34] vs. 0 [IQR: 0 to 1]), stent deployment (30 [IQR: 9 to 35] vs. 0 [IQR: 0 to 1]), stent dilation (16 [IQR: 8 to 30] vs. 0 [IQR: 0 to 1]), and total MES (93 [IQR: 59 to 136] vs. 16 [IQR: 7 to 36]). The number of patients with MES was higher with the FilterWire EZ versus MO.MA in phases 3 to 5 (100% vs. 27%; p < 0.0001). By multivariate analysis, the type of brain protection was the only independent predictor of total MES number. No significant difference was found in the number of patients with new post-CAS embolic lesion in the MO.MA group (2 of 14, 14%) as compared with the FilterWire EZ group (9 of 21, 42.8%). CONCLUSIONS In patients with high-risk, lipid-rich plaque undergoing CAS, MO.MA led to significantly lower microembolization as assessed by using MES counts.

Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression of coronary arterial narrowings in angina pectoris

Calcium antagonists and beta blockers may retard or inhibit atherogenesis. This study investigated whether nifedipine or propranolol influences coronary atherosclerosis in humans. In selected patients with effort angina and proven coronary artery disease, the cineangiographic pattern after 2-year therapy with nifedipine (group 1, 39 patients), propranolol (group 2, 36 patients) or isosorbide dinitrate (group 3, 38 patients) was compared to that before treatment. The disease evolved to a different extent in the 3 groups. Patients with evidence of progression of old narrowings and appearance of new narrowings were significantly fewer in group 1 (31% and 10%) than in group 2 (53% and 34%) and group 3 (47% and 29%). The number of stenoses with evidence of progression was significantly smaller after nifedipine (14), and larger after propranolol (39) compared with group 3 (24). Thus, nifedipine seemed more protective than the other 2 drugs against coronary atherosclerosis. The coronary risk factors were normal in the nifedipine group and remained so with treatment, suggesting that they were dissociated from influences on atherosclerosis. The evolution, as judged by the number of narrowings with progression, appeared significantly (p less than 0.01) worse with propranolol than with isosorbide dinitrate. Propranolol caused unfavorable modifications of serum lipids; there was a 28% increase in total triglycerides and a 25% decrease in high density lipoprotein cholesterol at 12 months in group 2.

Clinical and angiographic outcome after coronary arterial stenting with the Carbostent

The Carbostent is a new balloon-expandable, stainless steel, tubular stent with innovative multicellular design and unique turbastratic carbon coating (Carbofilm). This open nonrandomized 2-center study assesses the immediate and long-term clinical and angiographic outcomes after Carbostent implantation in patients with native coronary artery disease. The Carbostent was implanted in 112 patients with 132 de novo lesions. Most patients (55%) had unstable angina, and 38% of lesions were type B2-C. The mean lesion length was 12.5 +/- 7.0 mm, and 29% of lesions were > 15 mm in length. No stent deployment failure occurred, as well as acute or sub-acute stent thrombosis. The 6-month event-free survival was 84 +/- 4%. One patient with a stented right coronary artery and no restenosis at the angiographic follow-up died after 6 months of fatal infarction due to abrupt closure of a nontarget vessel. In-hospital non-Q-wave myocardial infarction occurred in 1 patient, and 11 patients had repeat target lesion revascularization (target lesion revascularization rate 10%). The 6-month angiographic follow-up was obtained in 108 patients (96%) (127 lesions). Angiographic restenosis rate was 11%. The loss index was 0.29 +/- 0.28. The results of this study indicate a potential benefit of Carbostent for the prevention of stent thrombosis and restenosis in these relatively high-risk patients. A larger trial is being planned to confirm these promising results.

Coronary adrenergic hyperreactivity in patients with syndrome X and abnormal electrocardiogram at rest

Syndrome X is characterized by an abnormal vasomotility of coronary microvessels. It is unknown whether the presence of an ischemic-like pattern in the electrocardiogram at rest (T-wave inversion) reflects a more severe vasomotion disturbance. Changes in coronary sinus flow (thermodilution) and epicardial vessel diameter (quantitative angiography) during adrenergic activation were measured with a standard cold pressor test in patients with syndrome X whose electrocardiogram at rest was normal (group 1: 17 patients) or showed stable, symmetrically inverted T waves (group 2: 22 patients). Cold pressor test increased mean blood pressure and rate-pressure product to a similar extent in both groups, increased coronary sinus flow in group 1 (88 +/- 29 to 119 +/- 36 ml/min; p less than 0.05) and not in group 2 (109 +/- 37 vs 104 +/- 36 ml/min; p = not significant), and decreased coronary resistance in group 1 (1.38 +/- 0.42 to 1.19 +/- 0.38 mm Hg/ml/min; p less than 0.05) and augmented it in group 2 (1.06 +/- 0.32 to 1.28 +/- 0.43 mm Hg/ml/min; p less than 0.02). During cold stimulus, the proximal and middle segments of epicardial arteries showed negligible changes in their lumen, whereas the distal segment dilated in group 1 (1.81 +/- 0.27 to 2.01 +/- 0.32 mm; p less than 0.05) and constricted in group 2 (1.82 +/- 0.12 to 1.62 +/- 0.20 mm; p less than 0.05). Differences in coronary hemodynamic and angiographic responses between the groups were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin alone antiplatelet regimen after intracoronary placement of the Carbostent™: The Antares study

The effect of stent coatings in preventing early thrombotic occlusion remains to be proved. The purpose of this study was to evaluate the safety and efficacy of the Carbostent™, a new coronary stent with a nonthrombogenic coating (Carbofilm™), in 110 consecutive patients (73.6% men, mean age 61 ± 9 years) who met prespecified clinical and angiographic inclusion criteria and were treated with aspirin monotherapy after stenting. Stable angina (75.5%), unstable angina (18.2%), and silent ischemia (6.3%) were clinical indications for coronary revascularization. Patients received 10,000 U of heparin and no IIb/IIIa inhibitors or postprocedural heparin. Complex lesion characteristics (B2, C) were present in 39 out of 129 (30.2%) lesions. Mean lesion length was 15.6 ± 7.4 mm, and 32% of the lesions were >15 mm (range 16–52 mm). Small coronary vessels (<3.0 mm) were treated in 28% of the cases. A total of 165 Carbostent™ were used in 129 coronary lesions of the 110 patients. Single‐vessel stenting was performed in 97 (88%) patients and multivessel stent placement in 13 (12%) patients. The mean length of the stented segment was 21 ± 13 mm (range 9–95 mm). Procedural and clinical success was achieved in all patients. At 1‐month follow‐up, there were no stent thrombosis or other major adverse cardiac events. We observed 2 (1.8%) non‐Q‐wave myocardial infarctions and 2 (1.8%) vascular complications. This study indicates that the Carbostent™ may prevent stent thrombosis in selected patients treated with aspirin only. A randomized study comparing aspirin alone versus combined ticlopidine and aspirin after Carbostent™ implantation will be needed to confirm these results. Cathet Cardiovasc Intervent 2002;55:150–156.

Acute coronary vasomotor effects of nifedipine and therapeutic correlates in syndrome X

In 18 patients (12 women) presenting with effort-induced chest pain and normal coronary angiograms (syndrome X), 10 mg sublingual nifedipine increased the lumen of major coronary arteries (quantitative angiography) by 13 +/- 10% (p less than 0.01), coronary blood flow (thermodilution) by 23 +/- 26% (p less than 0.05), norepinephrine plasma concentration by 60 +/- 42% (p less than 0.01) and decreased the global ST-segment shift during the effort stress test from 8.8 +/- 4.1 to 7 +/- 6.8 mm (p less than 0.03) at comparable maximal workload and at unchanged double product. There was a correlation (positive) of changes in flow with changes in coronary lumen diameter (r = 0.65, p less than 0.01) with ST-segment response to exercise (r = 0.83, p less than 0.001) and with (inverse) norepinephrine plasma concentration (r = -0.70, p less than 0.01); no correlation was found between ST-segment response and changes in arterial lumen diameter. In a few cases, nifedipine did not improve or even worsened the response to exercise; coronary flow was unchanged or decreased and norepinephrine plasma levels were modestly or greatly increased, respectively. After 4 weeks of treatment with nifedipine (10 to 20 mg 4 times daily), the effort ST-segment shift was further decreased to 4.4 +/- 3.5 mm (p less than 0.03) despite a slightly increased double product. Plasma norepinephrine values, as compared to those after acute nifedipine, were decreased by 40% in patients with further improvement and were unchanged in patients whose exercise performance did not vary.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful stent delivery with deep seating of 6 French guiding catheters in difficult coronary anatomy

Despite improvements in coronary stent design, delivery difficulties may still be encountered. Between April 1996 and September 1998, 945 patients underwent coronary stenting in our Institute. New 6 Fr Long Brite Tip (LBT) guiding catheters, allowing deep coronary artery intubation and increased backup support, were used in 25 (2.6%) of these patients presenting complex coronary anatomy and poor stent accessibility, electively in 3 (12%) and after stent delivery failure with multiple (2.1 ± 1.2) standard guiding catheters in 22 (88%). Deep coronary artery intubation (≥ 20 mm) was successfully performed in 22 (88%) patients and was associated with adequate pressure recording and contrast opacification without blood flow compromise. Ten (22.7%) Palmaz‐Schatz stents and 34 (77.3%) second‐generation stents of various lengths were successfully delivered to different coronary vessels (RCA = 15, LAD = 9, LCx = 1) in all patients in whom deep coronary intubation was obtained. These data demonstrate that deep coronary artery cannulation with LBT catheters is feasible and safe and may markedly increase the rate of stent delivery success in very complex coronary anatomy and when standard guiding catheters have failed. Cathet. Cardiovasc. Intervent. 48:279–284, 1999.

Comparison of coronary vasomotor responses to nifedipine in syndrome X and in Prinzmetal's angina pectoris

To test whether calcium channel blockade plays a similar role in the coronary vasomotion of patients with syndrome X (n = 29) and patients with Prinzmetals angina pectoris (n = 12), quantitative angiography was used to evaluate the effect of nifedipine (10 mg, sublingually) on the lumen diameter of proximal, mid and distal thirds of normal epicardial branches. The main differences in the coronary vasomotor reaction were uniform vasodilatation in Prinzmetals angina and a variable response to syndrome X, and a greater increase in the coronary lumen in patients with Prinzmetals angina as compared with those with syndrome X who showed vasodilatation. The variable response in syndrome X was not related to changes in diastolic pressure and cardiac output. Patients showing coronary constriction were those who responded to nifedipine with a higher degree of tachycardia, which might suggest a neural participation in the paradoxic reaction to this drug. In the Prinzmetal group, on the contrary, at a similar heart rate increase the pattern was invariably vasodilatation. Thus, calcium ions appear to have a different role in the coronary smooth muscle contractility of the 2 series of patients; in fact, in Prinzmetals angina nifedipine relaxed the coronary arteries to a greater degree and made them unresponsive to stimuli that were still able to cause vasoconstriction in patients with syndrome X.

Evidence of a shared mechanism of vasoconstriction in pulmonary and systemic circulation in hypertension: a possible role of intracellular calcium.

We investigated the hemodynamics of the greater and lesser circulation in 35 patients with primary hypertension, as well as the effects of calcium-channel blockade, to test whether a common factor may account for the excessive vascular resistance in the two circuits and whether intracellular calcium concentration ([Ca±±]i) may be involved. We proved that (1) elevated pulmonary arteriolar resistance (PAR) is not related to pulmonary blood flow and volume, pleural pressure, arterial oxygen or carbon dioxide tension and pH, left ventricular filling pressure and function; (2) systemic vascular resistance (SVR) significantly correlates with PAR; (3) calcium-channel blockade with nifedipine reduces systemic and pulmonary arterial pressures toward normal and significantly lowers both SVR and PAR; (4) the percent decrease in vascular resistance after nifedipine is related to the baseline level of resistance in both the greater and the lesser circulations. Failure of the mechanisms currently indicated as responsible for pulmonary vasoconstriction to explain convincingly the increased PAR, the correlation between SVR and PAR, as well as the qualitatively similar response to calcium-channel blockade suggest that a common factor produces vasoconstriction in the two circuits. A pathogenetic role of a primary disorder in [Ca±±]i cannot be excluded, but remains to proved.