Tirofiban and intracoronary stenting: evaluation of a new pharmacologic regimen.

Glycoprotein IIb/IIIa receptor antagonists are effective in decreasing cardiac events in patients with acute coronary syndromes. Abciximab reduces cardiac morbidity in patients receiving coronary stents. We sought to evaluate the use of tirofiban infusion in patients receiving intracoronary stents. We created a prospective registry of 50 consecutive patients in a single catheterization lab receiving a single vial of tirofiban (12.5 mg) and stenting. Successful stent deployment with a 30-day follow-up occurred in all patients. Clinical endpoints included death (0%), procedural infarct (4%), urgent revascularization (0%), stroke (0%), bleeding complication (4%), and vascular injury (0%). Tirofiban appeared to be a safe adjunctive therapy to coronary stenting.

Eosinophilia-myalgia syndrome and giant cell myocarditis: a case report and therapeutic approach.

Eosinophilia-myalgia syndrome and giant cell myocarditis are rare and unrelated inflammatory conditions. Both may result in intense inflammatory infiltrates with eosinophilic predominance. A case involving a patient in whom both conditions occurred and who required intensive, prolonged immunosuppressive therapy is presented.

Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo.

BACKGROUND: Although estrogens have been shown to be vasoactive hormones, the vascular effects of testosterone are not well defined. Like estrogen, testosterone causes relaxation of isolated rabbit coronary arterial segments. We examined the vasodilator effects of testosterone in vivo in the coronary circulation and the potential mechanisms of its actions. METHODS AND RESULTS: Using simultaneous intravascular two-dimensional and Doppler ultrasound, we examined the effect of intracoronary testosterone in coronary conductance and resistance arteries in 10 anesthetized dogs (5 male, 5 female). We also assessed the contribution of NO, prostaglandins, ATP-sensitive K+ channels, and classic estrogen receptors to testosterone-induced vasodilation. Testosterone induced a significant increase in cross-sectional area, average coronary peak flow velocity, and calculated volumetric coronary blood flow at the 0.1 and 1 mumol/L concentrations. This effect was independent of sex. Pretreatment with N omega-nitro-L-arginine methyl ester to block NO synthesis decreased testosterone-induced increase in cross-sectional area, average coronary peak flow velocity, and coronary blood flow. Pretreatment with glybenclamide to assess the role of ATP-sensitive K+ channels did not influence testosterone-induced dilation in epicardial arteries but did attenuate its effect in the microcirculation. Pretreatment with indomethacin or the classic estrogen-receptor antagonist ICI 182,780 did not alter testosterone-induced changes. CONCLUSIONS: Short-term administration of testosterone induces a sex-independent vasodilation in coronary conductance and resistance arteries in vivo. Acute testosterone-induced coronary vasodilation of epicardial and resistance vessels is mediated in part by endothelium-derived NO. ATP-sensitive K+ channels appear to play a role in the vasodilatory effect of testosterone in resistance arteries.

Options in antihypertensive drug therapy. Help in choosing from among the many agents.

The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V) states that "because diuretics and beta blockers are the only classes of drugs that have been used in long-term controlled trials and shown to reduce morbidity and mortality, they are recommended as first choice agents unless they are contraindicated or unacceptable." These guidelines are important, but practitioners should remember that many effective and well-tolerated classes of drugs are available for treating hypertension, and one may have greater usefulness than another in a given patient. For example, an angiotensin-converting enzyme inhibitor may be appropriate in a patient with hypertension and congestive heart failure or diabetic nephropathy. A calcium channel blocker may be beneficial in a patient with hypertension and concomitant angina. Results of prospective studies comparing classes of antihypertensive drugs and measuring clinically significant end points may help guide pharmacotherapy in the future.

Comparison of adenosine to dipyridamole in degree of coronary hyperemic response in heart transplant recipients.

Transplant coronary vasculopathy is associated with endothelial dysfunction. Microvascular function, assessed as coronary flow reserve, has been reported to be normal. We used intracoronary ultrasound technology to simultaneously assess conductance and resistance vessel function in response to standard dosages of the vasodilators adenosine and dipyridamole. Coronary hemodynamic changes were assessed in 11 heart transplant recipients, at a mean duration of 784 +/- 516 days after transplantation, using a 3.2Fr or 4.3Fr, 30-MHz ultrasound imaging catheter over a 0.014-inch Doppler guidewire. Measures of coronary average peak flow velocity (APV) and coronary cross-sectional area (CSA) were used to calculate volumetric flow during intravenous infusions of adenosine (140 micrograms/kg/min over 4 minutes) and dipyridamole (140 micrograms/kg/min over 4 minutes). Flow reserve was assessed as a ratio of maximal pharmacologically induced flow to steady baseline flow before infusion. Increase in APV (261.9% vs 194.6%, p = 0.005), lumenal CSA (+11.8% vs +4.2%, p = 0.01), peak volumetric blood flow (515.8 vs 317.2 ml/min, p = 0.007), and coronary flow reserve (2.93 +/- 0.74 vs 1.99 +/- 0.53, p < 0.001) were higher with adenosine than dipyridamole. Both agents caused similar decreases in systemic blood pressure and little change in heart rate. Adenosine appears to be a more potent coronary vasodilator than dipyridamole in denervated human transplant subjects. Adenosine has a vasodilator effect at the epicardial and microvascular levels, resulting in an overall increase in volumetric flow. Flow reserve in response to both endothelium-independent agents is decreased in comparison with previously established values, but the attenuation is greater with dipyridamole.

Impact of the operating physician on costs of percutaneous transluminal coronary angioplasty.

The hospital charts and billing records of 250 consecutive admissions for percutaneous transluminal coronary angioplasty (PTCA) at a university hospital were reviewed. Clinical characteristics, performing physician, angiographic features of the dilated lesion, procedural outcome, length of stay, and total and departmental hospital costs were recorded for each patient. We identified several independent predictors of hospital cost, including the physician ($4,400 increase from highest- to lowest-cost physician, p=0.004), age ($790 increase per 10-year increase in age, p=0.002), urgency of the procedure ($4,100 increase for urgent vs elective, p < 0.001), and combined angiography and PTCA ($850 increase vs separate angiography, p=0.04). Independent predictors of catheterization laboratory cost included the physician ($1,280 increase from highest- to lowest-cost physician, p=0.03), American College of Cardiology/American Heart Association lesion type B2 or C ($320 increase, p=0.03), and combined angiography and PTCA ($430 increase, p=0.003). Expensive operators used more catheterization laboratory resources than inexpensive operators; however, there are no significant differences in success rate or need for emergent bypass surgery between physicians. PTCA cost is determined by both patient characteristics and the performing physician. The increase in cost due to the physician was not explained by patient variables, lesions characteristics, success rate, or complications.

Coronary flow reserve: noninvasive measurement in humans with breath-hold velocity-encoded cine MR imaging.

PURPOSE: To measure coronary vasodilator reserve with breath-hold velocity-encoded cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: Eight healthy adult volunteers underwent 1.5-T MR imaging. Velocity-encoded cine images were acquired at seven to 13 temporal phases in 25 seconds, with k-space segmentation and view-sharing reconstruction (+/- 1 m/sec velocity-encoding value) (repetition time msec/echo time msec = 16/9). Flow velocity in the left anterior descending (LAD) artery was measured twice before and twice after administration of dipyridamole (0.56 mg per kilogram of body weight). RESULTS: Peak diastolic coronary flow velocity in the LAD artery was 14.8 cm/sec +/- 1.9 (mean +/- standard deviation) in the baseline state. It increased significantly (P< .01) to 46.3 cm/sec +/- 10.2 after dipyridamole administration, with an average coronary reserve of 3.14 +/- 0.59. Interstudy and interobserver reproducibilities for measurement of peak diastolic velocity were, respectively, 9.5% +/- 1.6 and 7.0% +/- .2.5 in the baseline state and 6.8% +/- 2.2 and 3.4% +/- 1.5 after dipyridamole administration. CONCLUSION: Breath-hold velocity-encoded cine MR imaging provided reproducible assessment of coronary flow reserve in humans.

Breath-hold MR measurements of blood flow velocity in internal mammary arteries and coronary artery bypass grafts.

Breath-hold velocity-encoded cine MR (VENC-MR) imaging is a feasible method for measuring phasic blood flow velocity in small vessels that move during respiration. The purposes of the current study are to compare breathhold VENC-MR measurements of flow velocities in the internal mammary arteries (IMA) with nonbreath-hold measurements and to characterize the systolic and diastolic flow velocity curves in a cardiac cycle in native IMA and IMA grafts. Flow velocity in 30 native IMA and 8 IMA grafts were evaluated with a breath-hold VENC-MR sequence with K-space segmentation and view-sharing reconstruction (TR/TE = 16/9 msec, VENC = 100 cm/s). In 10 native IMA, nonbreath-hold VENC-MR images were acquired as well for comparison. Breath-hold VENC-MR imaging showed significantly higher systolic and diastolic peak velocities in native IMA (43.1 cm/second +/- 15.0 and 10.0 cm/second +/- 4.8), in comparison to those of nonbreath-hold VENC-MR imaging (27.6 cm/second +/- 10.2 and 7.3 cm/second +/- 3.9, P < .05). The diastolic/systolic peak velocity ratio in the IMA grafts (.88 +/- .41) was significantly higher than that in native IMA (.24 +/- .08, P < .01). Interobserver variability in the flow velocity measurement was less than 4%. Breath-hold VENC-MR imaging demonstrated higher peak flow velocity in the IMA than nonbreath-hold VENC-MR imaging. This technique is a rapid and effective method for the noninvasive assessment of blood flow velocity in IMA grafts.

Cardiogenic shock: thrombolysis or angioplasty?

Cardiogenic shock (CGS) occurs in 3 to 20% of patients presenting with acute myocardial infarction (MI), and it generally involves dysfunction of at least 40% of the total myocardial mass. Prior to the advent of balloon angioplasty and thrombolysis, in-hospital mortality was greater than 75%. This mortality rate has been consistent in reported series despite the advent of cardiac intensive care units, vasopressor, inotropic, and vasodilator therapy. Intra-aortic balloon counterpulsation therapy provides hemodynamic improvement, and it may provide some mortality benefit when used in conjunction with appropriate revascularization. Survival studies have shown that patency of the infarct-related artery is a strong predictor of survival. No randomized trials have been completed to examine which reperfusion therapy best treats this emergent situation. Subgroup analysis of large scale, multicenter trials, although underpowered, has shown no improvement in mortality with use of thrombolytic agents, leading many to advise use of mechanical intervention. In patients who present with acute MI with contraindications to thrombolysis, primary angioplasty is the treatment of choice. At selected centers, primary angioplasty is comparable to or better than thrombolytic therapy for patients presenting with acute MI, with or without CGS. Studies examining angioplasty in patients with CGS have shown high procedural success rates (75%) and reduced in-hospital mortality (44%), particularly in those patients with successful revascularization. Emergency bypass surgery may improve survival, but it is costly, unavailable to many, and often leads to excessive delays in therapy. If available, we believe that primary angioplasty is the treatment of choice for patients with CGS.

MI survivors: using drug therapies to protect the heart.

Survivors of myocardial infarction are at increased risk for another MI, congestive heart failure, ventricular arrhythmias, and sudden death. Beta blockers reduce the rate of sudden death, reinfarction, and recurrent ischemia, particularly in elderly patients. Chronic aspirin therapy has shown significant reductions in cardiovascular morbidity and mortality and is recommended for all post-MI patients who can tolerate it. ACE inhibitor therapy has shown benefit in patients with impaired LV function. Identifying post-MI patients at risk for sudden death and preventing fatal arrhythmias has proven difficult. Class I antiarrhythmics should be avoided. Amiodarone and perhaps sotalol appear promising, but large-scale trials are still ongoing.

Increased prevalence of coronary ectasia in heterozygous familial hypercholesterolemia.

BACKGROUND: Although coronary atherosclerosis most commonly produces clinical effects as a result of stenosis, aneurysmal disease also occurs. We have found an increased prevalence of ectasia and aneurysmal disease in familial hypercholesterolemia (FH) suggesting a link between plasma lipoproteins and coronary aneurysms. METHODS AND RESULTS: In 197 asymptomatic subjects with FH, we examined the prevalence of ectasia and its association with coronary risk factors. An ectatic segment was defined as one with a luminal diameter > 1.5 times that of the adjacent normal segment, excluding poststenotic dilation. Among subjects with FH, 15% had ectasia compared with 2.5% of an age- and sex-matched control group of 198 subjects without FH presenting for coronary angiography (P < .001). These control patients had significantly more severe coronary atherosclerosis than patients with FH. Ectasia was 3 times more common in men than women (P < .025). Neither age nor hypertension was predictive. Although in part reflecting the striking sex differential, ectasia was strongly associated with a lower HDL cholesterol level (P = .003), a higher LDL/HDL ratio (P = .003), and to a lesser extent, a higher LDL cholesterol level (P = .07). No association was found with plasma triglycerides or very low-density lipoprotein cholesterol levels. Among FH patients, ectasia was strongly associated with an overall index of occlusive atherosclerotic disease, based on quantitative angiography (P = .004). Intracoronary ultrasound interrogation of aneurysmal segments revealed circumferential intimal thickening. CONCLUSIONS: Coronary ectasia is more prevalent in patients with FH than in other patients with coronary atherosclerosis and shows a strong inverse association with HDL cholesterol levels. This suggests that disordered lipoprotein metabolism in FH may predispose patients to aneurysmal coronary artery disease.

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation.

OBJECTIVES: This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND: Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS: We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS: No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS: Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.

Transcoronary and pulmonary vascular dynamics of endothelin-1 in heart transplant recipients.

BACKGROUND: Endothelin-1, a potent endothelium-derived vasoconstrictor peptide, has recently been shown to be elevated in heart transplant recipients and may be a participant in posttransplantation vasculopathy. METHODS: We measured peripheral venous endothelin-1 concentrations in eight heart transplant recipients and eight age- and gender-matched healthy controls. Subsequently, in 21 transplant recipients, right atrial, aortic, and coronary sinus plasma was obtained and endothelin-1 levels were measured. Potential correlations to donor and recipient age, cyclosporine levels, hemodynamic parameters, donor heart ischemic time, time from transplantation, and serum creatinine were examined. In eight more patients, right atrial levels of endothelin-1 were measured before and after endomyocardial biopsy to examine the effect of this procedure on endothelin-1 concentrations. RESULTS: Peripheral endothelin-1 concentrations were significantly higher in heart transplant recipients (45.6 +/- 1.8 versus 25.8 +/- 2.3, p < 0.001). Multiple regression analysis showed a significant correlation between right atrial endothelin-1 and pulmonary artery systolic pressure (r = 0.48), as well as serum creatinine (r = 0.52). No relation to blood pressure, right atrial pressure, pulmonary vascular resistance, recipient age, cyclosporine levels, or donor heart ischemic time was observed. In 11 patients, a 38% +/- 7% fall in endothelin-1 levels across the pulmonary bed was observed, suggesting extraction across the lung in these subjects. Nine patients had net release of endothelin-1 (95% +/- 26% rise) across the coronary vascular bed, whereas 12 patients showed net extraction (24% +/- 4% fall). Endomyocardial biopsy had no influence on endothelin-1 levels (prebiopsy: 48.3 +/- 1.7; postbiopsy: 42.3 +/- 2.34; p = Not significant). CONCLUSION: These findings suggest that endothelin-1 levels in transplant recipients may be influenced by renal function and may contribute to pulmonary hypertension. The significance of transcardiac release of endothelin in some patients is unclear: further studies are needed to determine the pathophysiologic significance of endothelin-1 in heart transplant recipients.

Thrombolysis after acute myocardial infarction. Who should be added to inclusion criteria?

Thrombolytic therapy has been proven to be highly effective and safe in patients presenting with acute myocardial infarction. Its use may reduce mortality rates by as much as 50%. Accelerated administration of tissue plasminogen activator (Activase) combined with intravenous heparin shows particular success in reducing mortality rates, especially in patients with anterior infarcts. However, strict compliance to the classic inclusion criteria has limited the number of patients, excluding several groups who have been shown to benefit from thrombolysis: The elderly appear to benefit from early thrombolysis even more than do their younger counterparts. Patients with inferior myocardial infarction and bundle-branch blocks also benefit. Recent trials suggest that thrombolytic therapy can be cautiously extended to patients presenting late (up to 24 hours) after onset of symptoms. Certain patients with a history of cerebrovascular disease or recent surgery, patients with severe hypertension, and those having undergone cardiopulmonary resuscitation should not necessarily be excluded from consideration.

Adjuvants to thrombolysis after acute myocardial infarction. Does adding antiplatelet agents, antithrombotics, or angioplasty make a difference?

Thrombolytic therapy markedly reduces mortality and improves left ventricular function in patients with acute myocardial infarction. Improvement may be even more substantial with adjuvant therapy. Aspirin has proved to be effective adjuvant therapy to thrombolysis. Other antiplatelet agents that may be even more effective or have an additive effect with aspirin are being studied. The role of antithrombotic agents, especially heparin, as adjuvant therapy remains unclear. Immediate cardiac catheterization with angioplasty has been used as adjunct therapy, but its routine use is not recommended. Instead, elective angioplasty (cardiac catheterization, with revascularization as indicated) should be undertaken in patients with recurrent ischemia. Angioplasty as an alternative to thrombolysis may be advantageous in certain patients, such as those presenting in cardiogenic shock or with contraindications to thrombolysis. The role of primary angioplasty in other groups (eg, the elderly, those with anterior myocardial infarction) remains unclear, and further trials are necessary before it can be recommended over thrombolytic therapy. Equipment needed for angioplasty limits its practicality, whereas thrombolytic therapy can be administered at most US hospitals.

Is there a role for positive inotropic agents in congestive heart failure: focus on mortality.

Congestive heart failure (CHF) is a common clinical syndrome that may result from a variety of etiologies. Impaired contractility can lead to pump failure and a number of hemodynamic and neurohormonal alterations. Vasodilator therapy improves symptoms and survival in patients with CHF due to systolic dysfunction. Inotropic therapy, on the other hand, has not been shown to improve survival and may even worsen survival. This article reviews the mechanism of action and clinical trials of inotropic therapy in patients with CHF.

Evaluating coronary artery disease noninvasively--which test for whom?

The generally accepted indications for stress testing in patients with coronary artery disease include confirming the diagnosis of angina, determining the limitation of activity caused by angina, assessing prognosis in patients with known coronary artery disease, assessing perioperative risk, and evaluating responses to therapy. In patients with a clinical scenario strongly suggestive of angina, testing is not necessary to diagnose coronary artery disease. The exercise treadmill-electrocardiogram test is the oldest and most extensively used stress test and can be reliably performed in patients who are clinically stable and who have an interpretable resting electrocardiogram. The addition of myocardial imaging agents such as thallium 201, technetium Tc 99m sestamibi, and technetium Tc 99m teboroxime increases the sensitivity and specificity for detecting coronary disease. Pharmacologic agents such as dipyridamole, adenosine, and dobutamine may be used in patients who cannot exercise adequately. Myocardial ischemia can also be evaluated by echocardiography, computed tomography, or magnetic resonance imaging, especially when additional information such as left ventricular and valvular function is desired. We review the indications for the noninvasive evaluation of coronary artery disease and the rationale for selecting a diagnostic test.

Differential contribution of nitric oxide to regulation of vascular tone in coronary conductance and resistance arteries: intravascular ultrasound studies.

We examined the role of nitric oxide in the maintenance of coronary vascular tone in 15 dogs. A 0.014 inch Doppler wire was introduced into the midsegment of the circumflex coronary artery and a 4.3F, 30 MHz two-dimensional ultrasound imaging catheter was introduced over the Doppler wire. Acetylcholine caused a dose-dependent vasodilation in both epicardial and resistance coronary arteries. However, N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthetase caused a dose-dependent vasoconstriction mainly in the epicardial coronary arteries, partially reversed by L-arginine. The vasodilator response to acetylcholine was inhibited by L-NAME only in the epicardial circulation. Thus using combined intracoronary two-dimensional and Doppler ultrasound, we have demonstrated both basal and acetylcholine-induced release of nitric oxide in epicardial coronary arteries. The failure of L-NAME to decrease basal and acetylcholine-induced increases in flow velocity suggests that endothelium-dependent relaxation in coronary resistance vessels may not be mediated by nitric oxide alone.

Contained rupture following percutaneous transluminal coronary angioplasty: long-term outcome.

Coronary artery aneurysm formation can occur as a complication of balloon angioplasty. We present a case of a contained rupture of the left circumflex artery following angioplasty which resulted in an unusual pseudoaneurysm on angiography at 3-year follow-up.