The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus.

* A significant proportion of men with erectile dysfunction (ED) exhibit early signs of coronary artery disease (CAD), and this group may develop more severe CAD than men without ED (Level 1, Grade A). * The time interval among the onset of ED symptoms and the occurrence of CAD symptoms and cardiovascular events is estimated at 2-3 years and 3-5 years respectively; this interval allows for risk factor reduction (Level 2, Grade B). * ED is associated with increased all-cause mortality primarily due to increased cardiovascular mortality (Level 1, Grade A). * All men with ED should undergo a thorough medical assessment, including testosterone, fasting lipids, fasting glucose and blood pressure measurement. Following assessment, patients should be stratified according to the risk of future cardiovascular events. Those at high risk of cardiovascular disease should be evaluated by stress testing with selective use of computed tomography (CT) or coronary angiography (Level 1, Grade A). * Improvement in cardiovascular risk factors such as weight loss and increased physical activity has been reported to improve erectile function (Level 1, Grade A). * In men with ED, hypertension, diabetes and hyperlipidaemia should be treated aggressively, bearing in mind the potential side effects (Level 1, Grade A). * Management of ED is secondary to stabilising cardiovascular function, and controlling cardiovascular symptoms and exercise tolerance should be established prior to initiation of ED therapy (Level 1, Grade A). * Clinical evidence supports the use of phosphodiesterase 5 (PDE5) inhibitors as first-line therapy in men with CAD and comorbid ED and those with diabetes and ED (Level 1, Grade A). * Total testosterone and selectively free testosterone levels should be measured in all men with ED in accordance with contemporary guidelines and particularly in those who fail to respond to PDE5 inhibitors or have a chronic illness associated with low testosterone (Level 1, Grade A). * Testosterone replacement therapy may lead to symptomatic improvement (improved wellbeing) and enhance the effectiveness of PDE5 inhibitors (Level 1, Grade A). * Review of cardiovascular status and response to ED therapy should be performed at regular intervals (Level 1, Grade A).

Markers of inflammation, thrombosis and endothelial activation correlate with carotid IMT regression in stable coronary disease after atorvastatin treatment.

BACKGROUND AND AIMS: MIAMI is a prospective multicenter clinical study designed to investigate the relationship between changes in carotid intima-media thickness (C-IMT) and changes in circulating markers of inflammation, thrombosis and endothelial activation in stable coronary patients treated for 20+/-3.7 months with 20mg/day atorvastatin. METHODS AND RESULTS: Eighty-five subjects had their C-IMT, blood lipids and soluble markers measured at baseline, at the 12th month and at the end of the study. Almost all soluble markers decreased upon treatment except for high-sensitivity C-reactive protein (hs-CRP), interleukin-18 (IL-18), tissue factor pathway inhibitor-free (TFPI-free) and soluble vascular cell adhesion molecules-1 (sVCAM-1) which did not change significantly, and interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and soluble CD40 ligand (sCD40L) which increased. sCD40L, fibrinogen, tissue factor pathway inhibitor-total (TFPI-total), soluble intercellular adhesion molecules-1 (sICAM-1), sE-selectin, interleukin-8 (IL-8) and von Willebrand factor (vWF) changed significantly even after application of the Bonferroni correction for multiple comparisons. Changes in lipids did not correlate with C-IMT regression either when considered singly or when combined in a lipid score. Changes in soluble markers correlated poorly with C-IMT regression when analyzed singly, but strongly when combined in relevant composite scores (inflammation/coagulation score, endothelial activation score, soluble markers score and total score). CONCLUSION: In patients with stable coronary artery disease treated with moderate doses of atorvastatin, carotid IMT regression correlated with changes of inflammation, thrombosis and endothelial activation profiles.

E-selectin and TFPI are associated with carotid intima-media thickness in stable IHD patients: the baseline findings of the MIAMI study.

OBJECTIVE: MIAMI was a prospective multicenter clinical study designed to investigate the relationship between changes in carotid intima-media thickness (C-IMT) and those in the levels of circulating markers of inflammation, thrombosis and endothelial dysfunction. The study was performed in a group of stable coronary patients treated for two years with a moderate dosage of atorvastatin (20mg/day). In this paper the cross-sectional relationship between C-IMT and the same circulating markers of inflammation, thrombosis and endothelial dysfunction measured at baseline was investigated. METHODS: Eighty-five subjects that had not used statins for at least two months were enrolled in the study. At time of enrollment, the levels of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha, high-sensitivity C-reactive protein (hs-CRP), tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), fibrinogen, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), and triglycerides were measured, in parallel with C-IMT assessment. RESULTS: In cross-sectional analyses, markers of endothelial perturbation (i.e. E-selectin) and TFPI were more strongly correlated with arherosclerotic burden than markers of inflammation. The baseline picture in this study indicates that E-selectin and TFPI are linked with atherosclerotic burden.

The great opportunity of the andrological patient: cardiovascular and metabolic risk assessment and prevention.

Andrologists, cardiologists and diabetologists (and general practitioners) have the great opportunity to collaborate and find shared clinical workup for the benefit of a large number of men. Several evidence established a link between erectile dysfunction (ED), cardiovascular disease (CVD), diabetes, and metabolic syndrome. Not only these conditions share many risk factors and pathophysiological mechanisms but also an emerging paradigm indicates that ED is, in fact, an independent marker of cardiovascular disease risk, CV events and CV mortality. However, there is no consensus on the best cardiologic investigation in men with ED with no known CVD and, on the contrary, on what is the clinical and prognostic role of detecting ED during cardiovascular investigation and CVD risk assessment. Only vasculogenic ED, which represents the most common type of organic ED, indeed represents a harbinger of CVD, especially for younger patients, and might be diagnosed by dynamic penile color doppler ultrasonography, which represents a real cardiovascular imaging technique that give evidence on the presence of systemic endothelial dysfunction and atherosclerosis. Furthermore, assessment of glucose and lipid metabolism is warranted as first step workup in all ED patients, and diabetologists should ask their patients for erectile function, address ED patients to andrologists, and consider vasculogenic ED in the context of the cardiovascular and metabolic workup and in the context of diabetic complications. Sexual symptoms (and testosterone levels) should sound as harbinger for cardiovascular and metabolic investigation and cardiologists and diabetologists have the opportunity to have a symptom (erectile dysfunction) and a vascular test (penile color doppler) that help them in better management of patients, their comorbidities and complications.

Pulmonary vascular supersensitivity to catecholamines in systemic high blood pressure.

Pulmonary pressure and arteriolar resistance are elevated in uncomplicated primary systemic hypertension. This study was carried out in 16 men with this form of hypertension and in 9 healthy men to compare 1) their pulmonary vascular reactivity to endogenous catecholamines released during mental arithmetic and cold pressor tests, and 2) the dose-response relation to exogenous epinephrine and norepinephrine. Arithmetic and cold pressor tests were associated, respectively, with a predominant increase in plasma epinephrine and norepinephrine concentration; changes were significantly greater in hypertensive men. During the two tests, pulmonary arteriolar resistance in the normotensive group was reduced by 13% and augmented by 7% of baseline, respectively, whereas it was raised by 31 and 70%, respectively, in the hypertensive group. In normal subjects, the dose (microgram)-response (delta dynes) relation to epinephrine was 1 = -4, 2 = -9, 3 = -9 and 4 = -10; to norepinephrine it was 2 = +3, 4 = +6, 6 = +7 and 8 = +7. In hypertensive patients, the respective relations were 1 = +18, 2 = +44, 3 = +59 and 4 = +77; and 2 = +39, 4 = +54, 6 = +76 and 8 = +98. Group differences were highly significant. In each of these circumstances, the driving pressure across the lungs was significantly augmented in the hypertensive but not the normotensive group. Both epinephrine and norepinephrine have a vasoconstrictor influence on the lesser circulation as a consequence of vascular overreactivity. The opposite changes in resistance between normotensive and hypertensive subjects produced by epinephrine suggest that a constrictor vascular supersensitivity becomes active in the pulmonary circuit with the development of systemic high blood pressure.

Ultra-low-dose CT for left atrium and pulmonary veins imaging using new model-based iterative reconstruction algorithm.

AIMS: To evaluate the feasibility of ultra-low-dose CT for left atrium and pulmonary veins using new model-based iterative reconstruction (MBIR) algorithm. METHODS AND RESULTS: Two hundred patients scheduled for catheter ablation were randomized into two groups: Group 1 (100 patients, Multidetector row CT (MDCT) with MBIR, no ECG triggering, tube voltage and tube current of 100 kV and 60 mA, respectively) and Group 2 [100 patients, MDCT with adaptive statistical iterative reconstruction algorithm (ASIR), no ECG triggering, and kV and mA tailored on patient BMI]. Image quality, CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of left atrium (LA) and pulmonary veins, and effective dose (ED) were evaluated for each exam and compared between two groups.No significant differences between groups in terms of population characteristics, cardiovascular risk factors, anatomical features, prevalence of persistent atrial fibrillation and image quality score. Statistically significant differences were found between Group 1 and Group 2 in mean attenuation, SNR, and CNR of LA. Significantly, lower values of noise were found in Group 1 versus Group 2. Group 1 showed a significantly lower mean ED in comparison with Group 2 (0.41 ± 0.04 versus 4.17 ± 2.7 mSv). CONCLUSION: The CT for LA and pulmonary veins imaging using MBIR is feasible and allows examinations with very low-radiation exposure without loss of image quality.

Correlates of plasma atrial natriuretic factor in health and hypertension.

Plasma concentrations of atrial natriuretic factor (ANF) were compared in normotensive subjects and subjects with untreated, uncomplicated essential hypertension (n = 21 pairs) matched for age, sex, and race. Plasma peptide values were slightly greater (45 +/- 3 vs 36 +/- 3 pg/ml; p less than 0.05) in the hypertensive group. On univariate analysis, age (r = 0.52, n = 47, p less than 0.001) and creatinine clearance (r = -0.30, n = 47, p less than 0.05) were significantly related to plasma ANF concentrations, but arterial pressure was not (r = 0.14, n = 47), in an extended group of normal subjects. In contrast, plasma ANF values were related to arterial pressure in both an extended group of subjects with untreated essential hypertension (r = 0.54, n = 38, p less than 0.001) and in our total heterogeneous pool of hypertensive patients (r = 0.46, n = 79, p less than 0.001), but weak positive associations with age and inverse relationships with creatinine clearance were not statistically significant in either hypertensive group. Similar weak inverse relationships between plasma ANF values and renin-angiotensin-aldosterone system activity were found in both normal and hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Low dose infusions of 26- and 28-amino acid human atrial natriuretic peptides in normal man.

To investigate the effects of a small rise in the plasma atrial natriuretic peptide (ANP) concentration, 6 normal subjects received 2-h low dose (2 pmol/kg.min) infusions of both 28 [human alpha hANP-(99-126)]- and 26 [human ANP-(101-126)]-amino acid peptides in a placebo-controlled study. Both peptides induced more than 2-fold increases in urinary sodium, calcium, and magnesium excretion. Effective renal plasma flow was slightly reduced, glomerular filtration rate did not change, and renal filtration fraction increased during the ANP infusions. Plasma renin, angiotensin II, and aldosterone concentrations fell by about 50%. Arterial blood pressure and plasma catecholamines did not change. Hematocrit and serum albumin concentrations rose significantly. ANP effects on urinary electrolytes and the renin-angiotensin-aldosterone system were sustained for over an hour after completion of the ANP infusions. The two peptides did not differ in their effects. These results are consistent with a physiological role for plasma ANP in the regulation of extracellular fluid volume and demonstrate that minor N-terminal truncation of alpha hANP has little effect on its biological activity.

Superior efficacy of propranolol versus nifedipine in double-component angina, as related to different influences on coronary vasomotility.

PURPOSE: 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 the 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. PATIENTS AND METHODS: The study was randomized, placebo-controlled, and crossover in design. Nineteen of the 24 subjects were men (mean group age, 59 years; range, 47 to 65 years). The study consisted of four four-day periods. The first and the fourth periods, during which patients received placebo, were single-blind. The treatment consisted of 80 mg of propranolol or 20 mg of nifedipine administered four times daily. The second and the third periods, during which patients received propranolol or nifedipine crossing over to the alternative drug in the next period, were double-blind and separated by a 24-hour interval. RESULTS: Propranolol fully abolished or reduced the number of spontaneous ischemic episodes in a significantly larger proportion of patients than did nifedipine; it was also effective in several cases in which nifedipine had failed or had even caused a paradoxic effect. Quantitative angiographic evaluation of the influences 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 one significant coronary stenosis in each patient showed that (1) after nifedipine, the lumen was unchanged in one, augmented in seven, and reduced in four cases; (2) 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 (3) in no case did treatment with propranolol vary the stenosis lumen by more than 0.3 mm. CONCLUSION: 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. Propranolol produces no important variations of the coronary stenotic lesions, causes a decrease of heart rate that facilitates coronary flow in diastole, and reduces the baseline metabolic demand of the heart so that the threshold of ischemia during critical reduction of coronary flow may become elevated.

Atrial natriuretic peptides and renin release.

The relationship between endogenous plasma concentrations of atrial natriuretic peptide and renin was examined in resting normal subjects and patients with cardiac impairment. To test the hypothesis that atrial natriuretic peptide inhibits renin secretion, intravenous infusions of atrial natriuretic peptide were administered to normal volunteers, patients with end-stage renal failure, and conscious dogs in both sodium-replete and sodium-depleted states. Plasma atrial natriuretic peptide and renin were inversely related in normal subjects (r = -0.52, n = 140, p less than 0.001), but a weak positive association between these two variables was observed in patients with cardiac impairment (r = 0.32, n = 60, p less than 0.02). Low doses of both 26- and 28-amino-acid human atrial natriuretic peptide (2 pmol/kg/minute for two hours) given to sodium-replete normal subjects halved plasma renin compared with time-matched placebo values (19 +/- 4 and 18 +/- 3 versus 36 +/- 8 microU/ml, p less than 0.001 for both). Incremental doses of synthetic atrial natriuretic peptide suppressed plasma renin below time-matched placebo values in both sodium-replete (maximal suppression 1.2 +/- 0.4 versus 8.6 +/- 1.4 microU/ml, p less than 0.001) and sodium-depleted (maximal suppression 18.9 +/- 4.9 versus 51 +/- 13 microU/ml, p less than 0.05) dogs. This effect was initially apparent at low doses of atrial natriuretic peptide (1 pmol/kg/minute), and renin suppression was maximal, in both states, with lesser doses of atrial natriuretic peptide than those at which maximal natriuresis was observed. Atrial natriuretic peptide administered to patients with end-stage renal failure (10 pmol/kg/minute for one hour) caused no change in plasma renin. These data confirm that atrial natriuretic peptide inhibits renin secretion in a dose-related manner and suggest that this action of the peptide is modified by both the baseline sodium status and renal function of the recipient.

Intrarenal beta-receptor and renal baroreceptor interaction in the control of the renin response to transient reduction of the renal perfusion pressure in man.

We have examined the mechanisms mediating the release of renin elicited in man by reduction of renal perfusion pressure. Fifteen patients with essential hypertension and six normotensive subjects were investigated during diagnostic renal arteriography. Renal neural receptors were inhibited by propranolol (10 mg i.v.) and activated by a standard cold pressor test. Vascular receptors were stimulated by unilateral reduction of renal perfusion pressure by 50%, using a balloon-tipped catheter. The stimulus caused release of renin. In hypertensives, arterial plasma renin increased by 44, 69 and 73% of control at 5, 15 and 30 min, respectively. Adrenergic activation by cold raised the arterial and the renal venous renin by approximately 50% of control and caused a fourfold rise when it was combined with the arterial obstruction. Following propranolol the renin response to reduction of the renal perfusion pressure was delayed and reduced, and cold stimulation, both alone and in combination with arterial obstruction, failed to stimulate renin release. Findings were qualitatively and quantitatively similar in the normotensive group. This study supports the hypothesis that the renin response to reduction of renal perfusion pressure in man results from an interaction of adrenergic and vascular receptors. It cannot be stated whether the former are synergistic or supplementary to the latter, even though adrenergic activation by cold stimulation provides evidence that a synergism between the two may exist.

Role of cine-fluoroscopy, transthoracic, and transesophageal echocardiography in patients with suspected prosthetic heart valve thrombosis.

Prosthetic heart valve thrombosis (PVT) is a rare but potentially life-threatening complication of heart valve replacement. An effective, quick, and easy diagnostic method is highly desirable. We evaluated the diagnostic efficacy of cine-fluoroscopy (CF), transthoracic (TTE), and transesophageal (TEE) echocardiography in 82 consecutive patients with mechanical valves and suspected PVT. Criteria for PVT were: leaflet(s) motion restriction at CF, increased Doppler gradients at TTE, and evidence of thrombi at TEE. Patients were divided in 4 groups (A, B, C, and D) according to results of CF and TTE. Group A was composed of 24 patients with positive CF and TTE. Thrombi were detected by TEE in all cases, suggesting that when both are positive, CF and TTE correctly identified PVT in all patients so that TEE may be deferred. Group B was composed of 12 patients with positive CF and negative TTE; TEE showed PVT in 4 patients (33%). These patients had very slight leaflet motion restriction as in the case of initial PVT. This suggests that CF compared with Doppler may identify patients with "hemodynamically significant" PVT. The remaining 8 patients in this group had monocuspid prostheses with negative TEE, suggesting that abnormal leaflet motion at CF may be due to functional changes. Therefore, TEE should always be performed in case of monocuspid prostheses with isolated CF abnormalities. Group C was composed of 18 asymptomatic patients with small-sized aortic prostheses and very high Doppler gradients on routine TTE. CF showed normal leaflet motion and TEE ruled out PVT in all cases outlining the diagnostic role of CF in this particular subset. Finally, group D was composed of 28 patients with negative CF and TTE. TEE did not show thrombi in 24 of 28 patients (86%), confirming that, when both yield negative results, CF and TTE are reliable methods to rule out valve thrombosis in most cases. However, in 4 of 28 patients (14%) TEE showed "nonobstructive" prosthetic thrombosis: these patients had mitral prostheses, chronic atrial fibrillation, and 3 of 4 had systemic embolisms. Thus, TEE should be performed in selected patients despite negative CF and TTE results. Sensitivity, specificity, and positive and negative predictive values were 87%, 78%, 80%, and 91% for CF and 75%, 64%, 57%, and 78% for TTE, respectively. CF and TTE correctly identified PVT in 70 of 82 patients (85%). TEE was actually required in 15% of the cases. Thus, CF and TTE are quick, effective, and complementary diagnostic tools to diagnose PVT in most patients. TEE still remains the gold standard technique in selected cases.

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)

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.

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)

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 Prinzmetal's 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 Prinzmetal's angina and a variable response to syndrome X, and a greater increase in the coronary lumen in patients with Prinzmetal's 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 Prinzmetal's 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.

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.

Elicitation of myocardial ischemia by nifedipine in a case of coronary artery fistula.

A 63-year-old woman had chest pain that worsened when nifedipine was given. She was found to have a right coronary-to-thorax angioma/fistula. Acute nifedipine administration elicited precordial symptoms, associated with ischemic changes in the inferior ECG leads and an obvious vasodilatation of the fistulous tract, suggesting that a nifedipine-induced "steal" phenomenon might be responsible for the paradoxic clinical response.

Nifedipine and angina pectoris. Short-term changes in quantitative coronary angiography with nifedipine and clinical response to treatment in effort-induced, mixed, and spontaneous angina pectoris.

Changes induced by nifedipine (10 mg sublingually) in the residual luminal diameter of significant (greater than 50 percent) coronary lesions were assessed angiographically in 69 patients with effort-induced angina (group 1), in 22 patients with mixed angina (group 2), and in 14 patients with Prinzmetal's angina (group 3). These changes were related to the clinical response to treatment with the same drug, as evaluated through diary records and Holter monitoring in the mixed (spontaneous component) and Prinzmetal forms and through exercise testing in effort-induced and mixed (effort-associated component) angina. In groups 1 and 2, segments of stenotic vessels showed either an increase or decrease or no change in diameter with the calcium antagonist; in group 3, the majority of the lesions had compliant portions which invariably responded with dilatation. Nifedipine failed to improve cases with exertional (20 percent [14/69] unchanged; 19 percent [13/69] worsened) and mixed (41 percent [9/22] exacerbated) forms; 100 percent of the 14 patients with the Prinzmetal form had relief of the anginal episodes. In group 1, the response to exercise tests was dissociated from the short-term vasomotor pattern, and the pressure-rate product failed to explain the clinical results. Forty-five percent (ten) of the patients in group 2 showed significant short-term widening of critical stenoses, as well as obvious improvement; patients who did worse with treatment in this group had reacted to nifedipine with narrowing of critical stenoses. These data suggest that the response to nifedipine of classic effort-induced angina is probably the net result of an interaction of changes in myocardial oxygen consumption and supply; coronary vasomotion has a role in mixed angina, and influences of nifedipine may be either favorable or unfavorable; stenotic lesions in the Prinzmetal form are quite sensitive to the relaxant action of calcium blockade, and this probably represents a background to the highly positive clinical response to treatment.