Role of calcium channel blocking agents in the prevention of atherosclerosis

Calcium channel blocking agents, although effective and widely used in the symptomatic therapy of hypertension and ischemic heart disease, have an uncertain effect on the development of coronary atherosclerosis, plaque rupture, and postrupture thrombosis. Both nifedipine and nicardipine have been shown to prevent the development of new coronary lesions but not the progression of existing lesions in prospective randomized angiographic studies. Verapamil, in contrast, failed to prevent the development of new coronary lesions and had no significant effect on the progression of existing lesions. Diltiazem, although not studied in patients with coronary atheroscleroses, has been shown to prevent the development of post-transplant coronary vascular disease. Despite the beneficial effects of nifedipine and nicardipine on new coronary lesion development, they have not been shown to reduce the incidence of recurrent ischemic events or mortality in the prospective randomized studies that demonstrated their effect on new coronary lesion development. A relatively new dihydropyridine calcium channel blocking agent, amlodipine, is hypothesized to prevent atherosclerosis due to its calcium channel blocking properties as well as by mechanisms independent of its calcium channel blocking properties. This agent has been selected for evaluation in the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) to explore whether the use of amlodipine over 3 years will reduce the incidence of early atherosclerotic lesions and, possibly, the progression of existing lesions in both the coronary and carotid arterial beds. Amlodipine could play an important future role in the secondary prevention of ischemic heart disease, but further study and a demonstration of a beneficial effect on recurrent ischemic events is required before any final conclusions concerning its effectiveness are reached.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44649/1/10557_2004_Article_BF00878569.pd

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 \ub1 6% vs. 86 \ub1 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. (Carotid Stenting in Patients With High Risk Carotid Stenosis ["Soft Plaque"] [MOMA]; NCT01274676) \ua9 2011 American College of Cardiology Foundation

Long-term successful coronary artery angioplasty in polycythemia vera

In a 65-year-old man with Polycythemia Vera, invalidating angina pectoris was associated with severe narrowing of the right coronary artery. After percutaneous coronary angioplasty (PTCA) the patient became symptom free and remained so for 12 months, while receiving an antiplatelet agent, a calcium antagonist and nitrate. Coronary angiography repeated after a year, because of reappearance of angina, documented good patency of the treated artery and some progression of a narrowing involving another coronary vessel. This is the first reported case of long-term success of PTCA in Polycythemia Vera, a disease exposed to a high risk of thrombosis and, possibly, of restenosis. It is undefined whether medical treatment contributed to the anatomical and clinical results. As far as a single case can say, Polycythemia Vera might not represent a prohibitive background for coronary PTCA

Doppler assessment of left ventricular filling pattern in silent ischemia in patients with Prinzmetal's angina

Spontaneous angina is an ideal condition in which to study left ventricular (LV) dysfunction induced by acute myocardial ischemia. In 6 patients with Prinzmetal's angina, LV diastolic function during 16 episodes of spontaneous angina was studied by simultaneous recordings of electrocardiographic (ECG), echocardiographic and hemodynamic parameters. In particular, pulsed Doppler echocardiography measured peak velocity of early (E) and late (A) transmitral flow and E/A ratio, as indexes of relative early versus late LV filling. During the ischemic attacks, the time sequence of pulsed Doppler echocardiographic and ECG changes showed 3 distinct phases: (1) "waxing phase: transmitral flow changes with minimal ECG modifications (E/A = 0.85 +/- 0.1); (2) "steady" phase: maximal ECG changes (E/A = 0.9 +/- 0.1); and (3) "waning" phase: regression of the ECG changes (E/A = 1.26 +/- 0.15). In each phase, E/A ratio showed a significant difference from the baseline value (E/A = 1.17 +/- 0.2) as a result of changes in E, suggesting that myocardial ischemia affects mainly the early phase of diastole. In the waxing phase, LV diastolic dysfunction preceded systolic abnormalities, as documented by a significant reduction of E/A ratio in the absence of alterations in LV ejection fraction, as well as in systemic arterial and pulmonary wedge pressures. Finally, all the recorded parameters were consistent with LV "contractile rebound" occurring in the waning phase and affecting both diastole and systole

[Greater efficacy of propranolol versus nifedipine in angina with 2 components, that results in varying influence on coronary vasomotility]

In 24 patients with stable spontaneous and effort-related angina, ischemic episodes at rest were not preceded by changes in circulatory variables (heart rate, systemic and pulmonary arterial pressures) that may raise myocardial oxygen consumption. We interpreted these episodes as caused by critical and reversible coronary flow reduction at the site of a stenotic lesion, and evaluated the clinical efficacy of nifedipine and propranolol in the treatment of this condition. Propranolol fully abolished or reduced the number of spontaneous ischemic episodes in a significantly larger number of patients than did nifedipine; it was also effective in several cases in whom nifedipine had failed or had even caused a paradoxic effect. Quantitative angiographic evaluation of the influence of nifedipine (Group 1, 12 patients, 10 mg sublingually) and propranolol (Group 2, 12 patients, 0.1 mg/kg intravenously) on the residual lumen diameter of 1 significant coronary stenosis in each patient showed that after nifedipine, the lumen was unchanged in 1, augmented in 7, and reduced in 4 cases; variations ranged between +1.59 and -1.2 mm, and their direction correlated closely with the influence of oral nifedipine on the episodes of spontaneous ischemia; and in no case did treatment with propranolol vary the stenosis lumen by more than 0.3mm. In this form of angina, a number of lesions seem to offer a compliant substrate for vasomotion and, possibly, for critical changes in flow. The vasomotor influences of nifedipine on these lesions are variable as well as the efficacy of the drug on the manifestations of ischemia at rest.(ABSTRACT TRUNCATED AT 250 WORDS

Hemodynamic response to oral prenalterol in dilated decompensated cardiomyopathy as a result of cardiac and vascular effects

The initial antifailure efficacy of beta-adrenergic agonists is generally lost during prolonged treatment. The reasons are not fully understood. In 11 patients with advanced cardiac decompensation due to dilated cardiomyopathy, prenalterol, a selective beta1 adrenergic agonist, improved the left ventricular contractility after acute intravenous and during prolonged oral administration. However, after periods of treatment ranging from 2 to 18 weeks, blood pressure and systemic vascular resistance were raised in each patient. These changes resulted in an increase of the left ventricular afterload which was such as to overwhelm the effects of the enhanced contractility, and to extinguish the initial improvement of the cardiac function and of the clinical condition. Stimulation of the presynaptical beta-receptors facilitating norepinephrine release or of the renin secretion by this beta1 agonist, may be the causes of the systemic vasoconstriction and of the loss of effectiveness in the long run

[Various clinical and vasomotor coronary responses to calcium block in mixed angina and Prinzmetal's angina, expression of various physiopathologic mechanisms]

Impedance to flow due to coronary spasm is currently interpreted as the mechanism of Prinzmetal angina. Flow impedance, probably of vasomotor origin, superimposed on severe coronary stenosis is also viewed as the trigger for the spontaneous component of mixed angina. The major question that we attempted to answer in this study was whether mixed angina may be considered a variant of the Prinzmetal form, or a particular manifestation of the classic effort form. For these purposes we investigated the acute vasomotor response to calcium channel blockade (nifedipine 10 mg sl) of both significant (greater than 50%) stenotic lesions and of normal coronary vessels in 22 patients with mixed angina and in 14 patients with Prinzmetal angina, and correlated it with the clinical response to treatment (nifedipine 20 mg qid). Calcium channel blockade, in fact, is considered as a specific remedy in the presence of an altered coronary vasomotility. The clinical response was evaluated through ambulatory Holter monitorings of 48 hour duration, while on placebo, nifedipine and placebo again. In mixed angina an angiographic evaluation showed that the residual lumen diameter of significant lesions was unchanged in 2, enhanced in 11 and reduced in 9 patients after sl nifedipine; lumen variations from base line ranged from +1.5 to -1.3 mm. Acute stenosis widening or narrowing correlated closely with the efficacy or not of the treatment. In the Prinzmetal group the vast majority of the lesions had compliant portions which invariably responded with dilatation (the residual coronary lumen increased by an average of 69% of base line); 100% of patients in this group responded favourably to treatment.(ABSTRACT TRUNCATED AT 250 WORDS