Mild renal insufficiency is associated with reduced coronary flow in patients with non-obstructive coronary artery disease.

Patients with chronic kidney disease (CKD) have increased risk for cardiovascular events. However, the association between these pathophysiological processes is unclear. Therefore, this study was designed to determine the association between early CKD and coronary microvascular disease in patients with normal or mildly diseased coronary arteries. A total of 605 patients with normal or mildly diseased coronary arteries based on angiography underwent coronary flow reserve (CFR) evaluation using intracoronary adenosine. Patients were divided based on glomerular filtration rate (GFR). CKD was defined as calculated GFR<60 ml/min/1.73 m(2). Patients with normal GFR (> or =60 ml/min/1.73 m(2), n=481) had higher CFR compared to those with CKD (n=124, CFR=3.0+/-0.8 vs 2.6+/-0.6, P<0.001, respectively). Patients with abnormal GFR were more likely to be older and of female gender, with greater prevalence of hypertension. Multiple logistic regression analysis adjusted for the aforementioned risk factors further supported the observed relationship. The current study shows that reduced renal function is associated with attenuated coronary vasodilator capacity in patients without obstructive coronary artery disease. The correlation between low GFR and reduced CFR may suggest parallel alterations in the renal and coronary microcirculation at the early stage of disease. Impairment in both microcirculatory beds may reflect an unmeasured risk factor induced by blunted renal function and add a burden to the increased propensity for cardiovascular events in CKD.

Incremental doses of intracoronary adenosine for the assessment of coronary velocity reserve for clinical decision making.

Achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of coronary flow reserve (CFR). The present study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilation of the coronary microcirculation when incremental doses are used, resulting in higher and more accurate coronary flow reserve measurements. Four hundred and fifty-seven patients were divided in two groups; group I (319 patients) comprised patients without angiographic evidence of significant coronary artery disease, while group II (138 patients) comprised patients with intermediate coronary stenoses (between 40% and 70% diameter stenosis). Coronary velocity reserve (CVR, a surrogate measurement for CFR) was measured during cardiac catheterization using a Doppler-tipped guidewire. Incremental doses of intracoronary adenosine (12 to 54 microg for the left coronary artery and 6 to 42 microg for the right coronary artery) were administered. There was a significant difference between the initial dose of adenosine and the subsequent incremental doses. Of a total of 479 observations, only 192 (40%) had the maximal CVR value at the first dose. Thirty-nine percent of the patients in group I and 27% in group II with an initial CVR value < 2.5 increased CVR to > or = 2.5 with incremental doses of adenosine. This study suggests that incremental doses of adenosine should be used to achieve maximal CVR for the assessment of the functional significance of coronary lesions. Cathet Cardiovasc Intervent 2001;54:34-40.

Pathophysiology, diagnosis, and current management strategies for chest pain in patients with normal findings on angiography.

Chest pain syndromes in patients with normal angiographic findings represent a multifactorial pathophysiologic state, which may range from abnormalities in pain perception to abnormalities in endothelial- and non-endothelial-dependent coronary flow reserve associated with myocardial ischemia. Treatment begins with an accurate diagnosis by obtaining a comprehensive history and performing a physical examination, followed possibly by performing functional angiography in those who continue to have symptoms. This approach may help to determine appropriate treatment.

Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries.

OBJECTIVES: This study evaluates the impact of obesity on coronary endothelial function in patients with normal or mild coronary artery disease. BACKGROUND: The American Heart Association (AHA) has recently classified obesity as a modifiable risk factor for coronary heart disease. METHODS: A total of 397 consecutive patients with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine and nitroglycerin. Patients were divided into three groups based on the body mass index (BMI): Group 1, patients with a BMI <25 (n = 117, normal weight); Group 2, patients with a BMI 25-30 (n = 149, overweight) and Group 3, patients with a BMI >30 (n = 131, obese). RESULTS: There were no significant differences among the groups in regard to other cardiovascular risk factors, except that overweight but not obese patients were significantly older than normal-weight patients (47 +/- 1 years in Group 1, 53 +/- 1 years in Group 2 and 50 +/- 1 years in Group 3, p < 0.001). The percent change of coronary blood flow to acetylcholine (%delta CBF Ach) was significantly lower in the obese patients than in the normal-weight group (85.2 +/- 12.0% in Group 1, 63.7 +/- 10.0% in Group 2 and 38.1 +/- 9.6% in Group 3, p = 0.009). By multivariate analysis, overweight (odds ratio, 1.55; 95% confidence interval, 1.2-2.0) and obesity (odds ratio, 2.41; 95% confidence interval, 1.5-4.0) status were independently associated with impaired coronary endothelial function. CONCLUSIONS: The study demonstrates that obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries.

Application of the New York State PTCA mortality model in patients undergoing stent implantation.

BACKGROUND: This study applied the New York State conventional coronary angioplasty (PTCA) model of clinical outcomes to evaluate whether it has relevance in the current era of stent implantation. The model was developed in 62 670 patients treated with conventional PTCA from 1991 to 1994 to risk adjust mortality and bypass surgery after PTCA. Since then, stents have become the dominant form of intervention. Whether that model remains relevant is uncertain. METHODS AND RESULTS: All patients undergoing stenting at the Mayo Clinic from 1995 to 1998 were analyzed for in-hospital mortality, bypass surgery performed after attempted stenting, and longer-term mortality. No patients were excluded. The New York model was used to risk adjust and predict in-hospital and follow-up mortality. There were 3761 patients with 4063 procedural admissions for stenting; 6,472 target vessel segments were attempted, and 96.1% of procedures were successful. With the New York multivariable risk factor equation, 79 in-hospital deaths were expected (1.95%); 66 deaths (1.62%) were observed. The New York model risk score in a logistic regression model was the most significant factor associated with in-hospital mortality (OR, 1.86; P<0.001). During a mean follow-up of 1.2+/-1.0 years, there were 154 deaths. Multivariable analysis documented 6 factors associated with subsequent mortality; New York risk score was the most significant (chi(2)=16.64, P=0.0001). CONCLUSIONS: Although the New York mortality model was developed in an era of conventional angioplasty, it remains relevant in patients undergoing stenting. The risk score derived from that model is the variable most significantly associated with not only in-hospital but also longer-term outcome.

Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy.

OBJECTIVES: The purpose of this study was to evaluate the association between hypertension and left ventricular hypertrophy (LVH) with both coronary vascular remodeling and endothelial function. BACKGROUND: The association between endothelial and nonendothelial coronary flow reserve with vascular remodeling in patients with hypertension and LVH is still unclear. METHODS: One hundred and eleven patients with normal or mildly diseased coronary arteries at angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Patients were divided into three groups: group 1: n = 13, hypertensive patients with LVH; group 2: n = 30, hypertensive patients without LVH; group 3: n = 68, normotensive patients. Vessel and lumen area and atherosclerotic plaque area were evaluated. Vascular reactivity was examined using intracoronary adenosine and acetylcholine. RESULTS: Vessel area in group 1 (with LVH) was significantly (p < 0.01) greater than that in group 2 (without LVH), whereas, vessel area in both groups 1 and 3 was similar (12.8 +/- 0.8 mm2, 10.7 +/- 0.4 mm2 and 11.5 +/- 0.3 mm2). Coronary blood flow at baseline for patients in group 1 (with LVH) was significantly greater than it was for patients in groups 2 and 3 (81.1 +/- 9.9 ml/min, 56.5 +/- 6.2 ml/min and 48.1 +/- 3.2 ml/min, both p < 0.05). In comparison with groups 2 and 3, the response to both acetylcholine and adenosine was significantly impaired in patients with LVH. CONCLUSIONS: The current study demonstrates that hypertension with LVH is associated with both coronary vascular remodeling and attenuated endothelial and nonendothelial coronary flow reserve.

Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

BACKGROUND: Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. METHODS AND RESULTS: Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. CONCLUSIONS: Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.

Cholesterol-lowering treatment is associated with improvement in coronary vascular remodeling and endothelial function in patients with normal or mildly diseased coronary arteries.

Coronary vascular remodeling and altered endothelial function have been described in the early stages of native atherosclerosis. The purpose of this study was to evaluate the association between cholesterol-lowering therapy and coronary vascular remodeling and endothelial function in patients with normal or mildly diseases coronary arteries. Patients (N=101) with normal or mildly diseased coronary arteries by coronary angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Vessel and lumen area, atherosclerotic plaque area, and plaque morphology were evaluated. Vascular reactivity was examined with the use of intracoronary adenosine, acetylcholine, and nitroglycerin. Patients were divided into 3 groups based on the total cholesterol levels: group 1 (n=25), patients with a history of hypercholesterolemia adequately treated (total cholesterol <240 mg/dL); group 2 (n=26), patients with hypercholesterolemia not adequately controlled (total cholesterol >/=240 mg/dL); and group 3 (n=50), patients without hypercholesterolemia. Vessel area and lumen area were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: vessel area 11.9+/-0.5, 10.6+/-0.4, and 11.8+/-0.4 mm(2), both P<0.05; lumen area 8.3+/-0.4, 6.9+/-0.3, and 8.9+/-0.3 mm(2), both P<0.01). However, plaque areas in groups 1 and 2 were similar. Furthermore, acetylcholine-induced percent increases in coronary blood flow were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: 70.5+/-20.1%, 22.8+/-13.7%, and 68.6+/-14.8%, both P<0. 05). Cholesterol-lowering treatment is associated with an improvement in coronary lumen area that results not from a decrease in plaque area but from an increase in vessel area, reflecting vascular remodeling. Additionally, this adaptive process may occur in association with an improvement of endothelium-dependent vasodilation of the resistance coronary artery.

Systemic amyloidosis presenting with angina pectoris.

BACKGROUND: Manifestations of cardiac amyloidosis may include congestive heart failure and sudden cardiac death. Although vascular involvement in patients with amyloidosis is common, systemic amyloidosis presenting with angina is rare. OBJECTIVES: To report on patients with systemic amyloidosis presenting with angina pectoris. DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Five patients who presented with angina pectoris and normal coronary angiogram as the initial manifestation of systemic amyloidosis. MEASUREMENTS: Endothelial-dependent and endothelial-independent coronary flow reserve. RESULTS: All patients had coronary flow reserve abnormalities and subsequently developed congestive heart failure and systemic manifestations of amyloidosis. Histologic evaluation revealed amyloid deposition in the intramyocardial coronary vessels. CONCLUSIONS: Cardiac amyloidosis can present as angina pectoris associated with coronary flow reserve abnormalities despite normal coronary angiograms. This finding may have major therapeutic and prognostic implications in this patient population.

Measuring maximal percent area stenosis poststent placement with intracoronary Doppler and the continuity equation and correlation with intracoronary ultrasound and angiography.

Quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) are methods for anatomic assessment of stent deployment. Intracoronary Doppler is primarily a method for the physiologic assessment of coronary stenoses. It correlates well with traditional noninvasive measurements of lesion significance. Intracoronary Doppler was used for the anatomic assessment of de novo coronary artery stenosis with variable success; however, its use for anatomic assessment of adequate stent deployment is unavailable. A rapid, automated software program was developed based on a modified continuity equation to calculate the maximal in-stent percent area stenosis by comparing the maximal in-stent velocity to an average reference velocity (proximal and distal). This study was designed to compare the Doppler method of an anatomic assessment with QCA and ICUS in 15 patients. Physiologic success of stent deployment was determined by the distal coronary flow reserve to 24 to 36 microg of intracoronary adenosine. Following successful stent deployment, distal coronary flow reserve increased significantly from a baseline of 1.6 +/- 0.5 to 2.9 +/- 1.1. There was a significant correlation between the maximal in-stent percent area stenosis as measured by Doppler and both QCA (r = 0.78, p <0.01) and ICUS (r = 0.84, p <0.01). This study demonstrates that maximal in-stent percent area stenosis can be measured by intracoronary Doppler and a novel software program. The intracoronary Doppler guidewire method can assess the adequacy of stent deployment using both anatomic and physiologic principles and may supplement other quantitative methodologies.

Variability of myocardium at risk for acute myocardial infarction.

The objective of this study was to assess the variability in myocardium at risk and relate this to coronary angiographic variables. One hundred ninety-seven patients with > or = 1-mm ST-segment elevation in 2 contiguous electrocardiographic leads, without prior myocardial infarction, were injected with technetium-99m sestamibi acutely before reperfusion therapy. The perfusion defect was quantified to determine myocardium at risk for infarction. Patients underwent coronary angiography to determine the infarct-related artery and to classify the occlusion as proximal or not proximal. Collateral and anterograde (Thrombolysis In Myocardial Infarction [TIMI] trial) flow were assessed in a subset of 83 patients with angiography before direct angioplasty. Myocardium at risk for infarction in the distribution of the left anterior descending coronary artery was significantly greater (p <0.0001) than that in the circumflex or right coronary artery. In the left anterior descending coronary artery distribution, myocardium at risk for infarction was significantly larger for proximal occlusions (p <0.0001). There was a trend toward greater myocardium at risk for infarction of proximal occlusions (p = 0.14) of the left circumflex but not for proximal occlusions in the right coronary artery distribution (p = 0.47). Multivariate analysis revealed that the infarct-related artery (p <0.0001), TIMI flow (p = 0.0002), and proximal location (p = 0.09) in the infarct-related artery were independent predictors of myocardium at risk for infarction. Thus, infarct-related artery, TIMI flow, and proximal location of occlusion in the infarct-related artery influence the myocardium at risk for infarction, which is highly variable for given location of occlusion.

Prevalence of coronary blood flow reserve abnormalities among patients with nonobstructive coronary artery disease and chest pain.

OBJECTIVE: To determine the prevalence of abnormalities in endothelium-dependent and endothelium-independent coronary flow reserve among patients with non-obstructive coronary artery disease and chest pain. MATERIAL AND METHODS: We studied endothelium-dependent (after infusion of 10(-6) M to 10(-4) M of acetylcholine) and endothelium-independent (after administration of 18 to 36 micrograms of adenosine) coronary flow reserve among patients with nonobstructive coronary artery disease and chest pain who were undergoing assessment at Mayo Clinic Rochester. Coronary blood flow was derived from coronary artery diameter assessed by quantitative angiography and Doppler flow velocities. RESULTS: The cohort consisted of 203 patients (158 female and 45 male patients), who ranged in age from 17 to 78 years (mean, 51). Most patients (92%) had at least one risk factor for atherosclerosis; a substantial proportion had undergone extensive cardiac and noncardiac evaluation. Whereas 41.5% of the patients had normal coronary flow reserve, 58.5% had an abnormal response: 11.3% an impaired response to adenosine (flow velocity ratio of 2.5 or less), 29.2% an impaired response to acetylcholine (flow reserve ratio of 1.5 or less), and 18% a combined abnormality. No correlation (r2 = 0.03) was noted between endothelium-dependent and endothelium-independent flow reserve. CONCLUSION: Most study patients with chest pain and nonobstructive coronary artery disease undergoing coronary vasomotor evaluation had risk factors for coronary artery disease and diverse abnormalities in endothelium-dependent or endothelium-independent coronary flow reserve (or both). These findings underscore the need for a comprehensive assessment.

Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement.

Increased basal epicardial tone may attenuate the coronary flow reserve (CFR) by causing vasodilatation of resistance vessels. We examined the effect of basal epicardial tone on the endothelium-independent CFR measurements in subjects with nonobstructive coronary disease. Patients underwent evaluation of endothelium-independent CFR using adenosine (18-36 microg) and endothelium-dependent CFR using acetylcholine (10(-6) M-10(-4) M), both administered intracoronary. CFR to adenosine, presented as the ratio of Doppler flow velocities post- and pre-adenosine, was measured at baseline and after intracoronary nitroglycerin (200 microg). Nitroglycerin increased the coronary artery diameter by 19.7 +/- 2.5%, and decreased the coronary vascular resistance from 3.0 +/- 0.2 mm Hg/ml/min to 1.8 +/- 0.1 mm Hg/ml/min (p < 0.0001). The response to adenosine at baseline and after nitroglycerin was similar (CFR ratio of 2.52 +/- 0.09 and 2.57 +/- 0.10, respectively, p = NS). The effect of nitroglycerin on the response to adenosine did not correlate with coronary endothelial function (r2 = 0.06, p = 0.13). The basal epicardial tone does not affect CFR measurements in patients with angina and nonobstructive coronary disease.

Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans.

BACKGROUND: Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine. Thus, the present double-blind, randomized study was designed to test the hypothesis that long-term, 6-month supplementation of L-arginine, the precursor of the endothelium-derived vasodilator NO, reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive coronary artery disease. METHODS AND RESULTS: Twenty-six patients without significant coronary artery disease on coronary angiography and intravascular ultrasound were blindly randomized to either oral L-arginine or placebo, 3 g TID. Endothelium-dependent coronary blood flow reserve to acetylcholine (10(-6) to 10(-4) mol/L) was assessed at baseline and after 6 months of therapy. There was no difference between the two study groups in clinical characteristics or in the coronary blood flow in the response to acetylcholine at baseline. After 6 months, the coronary blood flow in response to acetylcholine in the subjects who were taking L-arginine increased compared with the placebo group (149 +/- 20% versus 6 +/- 9%, P < 0.05). This was associated with a decrease in plasma endothelin concentrations and an improvement in patients' symptoms scores in the L-arginine treatment group compared with the placebo group. CONCLUSIONS: Long-term oral L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant improvement in symptoms and a decrease in plasma endothelin concentrations. This study proposes a role for L-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease.

Summary of the Mayo Clinic experience with direct left ventricular puncture.

Hemodynamic assessment of patients with prosthetic valves can be challenging. Noninvasive techniques may be limited by interference from the prosthetic material, whereas access to the left ventricle for direct pressure measurements often is not possible using common methods. The technique of direct, percutaneous left ventricular puncture has been proven to be a safe method that often provides needed data to help manage difficult clinical situations. We report our 8-yr experience with this technique for assessment of patients with valvular prostheses. Direct left ventricular puncture is a safe technique in patients with prior cardiac surgery and provided significant diagnostic information in the set of patients with multiple valvular prostheses.