Thomas Wolford

Cardiopulmonary Exercise Testing Identifies Low Risk Patients With Heart Failure and Severely Impaired Exercise Capacity Considered for Heart Transplantation

OBJECTIVES The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk. BACKGROUND Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (VO2) < or = 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size. METHODS Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise VO2 < or = 14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk. RESULTS The 55% 3-year survival rate of the 77 patients with a peak exercise VO2 < or = 14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak VO2 < or = 50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1. CONCLUSIONS Peak exercise SBP and percent predicted peak exercise VO2 are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise VO2 < or = 14 ml/min per kg.

Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements.

OBJECTIVES The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. BACKGROUND The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. METHODS Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean +/- SD diameter narrowing 54 +/- 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient < 25 mm Hg, or both. Patients were followed up for 9 +/- 5 months (range 6 to 30). RESULTS In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 +/- 0.32 vs. 1.3 +/- 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 +/- 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 +/- 9 vs. 45 +/- 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. CONCLUSIONS These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty.

Assessing the hemodynamic significance of coronary artery stenosis: Analysis of translesional pressure-flow velocity relations in patients☆

OBJECTIVES The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. BACKGROUND Determination of the clinical and hemodynamic significance of coronary artery stenoses is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. METHODS Using a 0.018-in. (0.046 cm) intracoronary Doppler-tipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients < 20 mm Hg, and Group B (n = 28) had gradients > or = 20 mm Hg. RESULTS Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients > or = 20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 +/- 1.0) than in group A (1.1 +/- 0.3, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio < 1.7 had a translesional gradient > 30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. CONCLUSIONS These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.

Determination of Angiographic (TIMI Grade) Blood Flow by Intracoronary Doppler Flow Velocity During Acute Myocardial Infarction

BACKGROUND This study compared angiographically graded coronary blood flow with intracoronary Doppler flow velocity in patients during percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction. Different TIMI angiographic flow grades (flow grades based on results of the Thrombolysis in Myocardial Infarction trial) have been associated with different clinical results after reperfusion for acute myocardial infarction. However, intracoronary blood flow velocity has not been compared with the angiographic method of determining flow grade in patients. METHODS AND RESULTS Coronary flow velocity (measured by use of a Doppler guidewire) during primary or rescue PTCA in 41 acute myocardial infarction patients was compared with TIMI grade and cineframes-to-opacification count. Before PTCA, 34 patients had TIMI grade 0 or 1, 5 had TIMI grade 2, and 2 had TIMI grade 3 flow in the infarct artery. Flow velocity was similar among patients with TIMI grades 0, 1, or 2 but was lower than in those with TIMI grade 3 flow (9.4 +/- 5.4 versus 16.0 +/- 5.4 cm/s for TIMI grades < or = 2 versus TIMI grade 3, respectively; P < .05). After PTCA, 1 patient had TIMI grade 1, 5 had TIMI 2, and 35 had TIMI 3 flow. Poststenotic flow velocity increased from 6.6 +/- 6.1 to 20.0 +/- 11.1 cm/s (P < .01). TIMI grade 3 flow increased to 21.8 +/- 10.9 cm/s (P < .05 versus before PTCA). Although post-PTCA flow velocity correlated with angiographic cineframes-to-opacification count (r = .45; P < .02) for TIMI grade 3, there was a large overlap with TIMI grades < or = 2 that had low flow velocity (< 20 cm/s). Nine of 11 clinical events (unstable angina and coronary artery bypass graft surgery) occurred in patients with low coronary flow velocity. CONCLUSIONS Determination of flow velocity after reperfusion may enhance patient characterization and provide the physiological rationale for clinical variations after reperfusion therapy.

Role of Coronary Artery Lumen Enlargement in Improving Coronary Blood Flow After Balloon Angioplasty and Stenting: A Combined Intravascular Ultrasound Doppler Flow and Imaging Study

OBJECTIVES This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. BACKGROUND Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in > or = 50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. METHODS To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. RESULTS The percent diameter stenosis decreased from (mean +/- SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89 +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 +/- 2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). CONCLUSIONS In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.

Abnormal Coronary Flow Velocity Reserve After Coronary Artery Stenting in Patients Role of Relative Coronary Reserve to Assess Potential Mechanisms

BACKGROUND Absolute coronary flow velocity reserve (CVR) after stenting may remain abnormal as a result of several different mechanisms. Relative CVR (rCVR=CVR(target)/CVR(reference)) theoretically normalizes for global microcirculatory disturbances and facilitates interpretation of abnormal CVR. METHODS AND RESULTS To characterize potential mechanisms of poststent physiology, CVR was measured using a Doppler-tipped angioplasty guidewire in 55 patients before and after angioplasty, after stenting, and in an angiographically normal reference vessel. For the group, the percent diameter stenosis decreased from 75+/-13% to 40+/-18% after angioplasty and to 10+/-9% (all P<0.05) after stent placement. After angioplasty, CVR increased from 1.63+/-0.71 to 1.89+/-0.55 (P<0.05) and after stent placement, to 2.48+/-0.75 (P<0.05 versus pre- and postangioplasty). After angioplasty, rCVR increased from 0.64+/-0.26 to 0.75+/-0.23 and after stent placement to 1.00+/-0.34. In 17 patients with CVR(stent) < or = 2.0, increased basal coronary flow, rather than attenuated hyperemia, was responsible in large part for the lower CVR(stent) compared with patients having CVR(stent) >2.0. In 8 patients with CVR(stent) <2.0, a normal rCVR supported global microvascular disease. The subgroup of 9 patients with CVR(stent) <2.0 and abnormal rCVR (16% of the studied patients) may require a pressure-derived fractional flow reserve to differentiate persistent obstruction from diffuse atherosclerotic disease or microvascular stunning. CONCLUSIONS Although a majority of patients after stenting normalize CVR for the individual circulation (ie, normal CVR or normal rCVR), in those with impaired CVR(stent), the analysis of coronary flow dynamics suggests several different physiological mechanisms. Additional assessment may be required to fully characterize the physiological result for such patients to exclude remediable luminal abnormalities.

Long-Term Cardiopulmonary Exercise Performance After Heart Transplantation

Functional capacity is an important outcome variable for heart transplantation, but there are few data that examine the temporal relation and duration of improvement in cardiopulmonary exercise performance after cardiac transplantation. Cardiopulmonary exercise performance was measured in 140 patients who underwent 426 treadmill exercise tests up to 9 years after cardiac transplantation. Univariate and multivariate analyses were used to predict postoperative improvement in functional capacity. Peak oxygen consumption (VO2) significantly improved from 14.2 +/- 3.7 ml/min/kg before to 21.4 +/- 5.6 ml/min/kg at a mean of 11.2 +/- 3.0 months after the transplant procedure (p < 0.001). When peak aerobic capacity was compared with a normal population, peak VO2 was < 50% of predicted in only 9 patients (12%), from 50% to 70% in 34 patients (44%), from 70% to 90% of predicted in 24 patients (31%); 10 patients (13%) were able to achieve > 90% of peak predicted VO2. The improvement seen at 6 months did not significantly change over 9 years of follow-up. Significant preoperative univariate predictors of.1-year postoperative improvement in peak VO2 were preoperative peak VO2 (p = 0.004), age (p < 0.001), ischemic cardiomyopathy (p = 0.007), and preoperative left ventricular ejection fraction (p < 0.001). Peak VO2 at 1 year in patients able to perform the test was not significantly influenced by acute rejection episodes, donor body surface area, or donor/recipient size ratio. In conclusion, exercise capacity is significantly improved within 6 months after cardiac transplantation, and maintained as long as 9 years after procedure. The magnitude of postoperative improvement is inversely related to preoperative peak VO2 and age.

Comparison of pressure-derived fractional flow reserve with poststenotic coronary flow velocity reserve for prediction of stress myocardial perfusion imaging results.

The physiologic importance of coronary stenoses can be assessed indirectly by stress myocardial perfusion imaging or directly by translesional pressure and flow measurements. The aims of this study were to compare myocardial fractional flow reserve (FFRmyo), a recently proposed index of lesion significance derived from hyperemic translesional pressure gradients, with directly measured poststenotic flow velocity reserve for the prediction of myocardial perfusion stress imaging results in corresponding vascular beds. Poststenotic coronary flow velocity (0.018-inch guide wire) and translesional pressure gradients (2.7F fluid-filled catheter) were measured at baseline and after intracoronary adenosine (12 to 18 micrograms) in 70 arteries (diameter stenosis: mean 56% +/- 15%, range 14% to 94% by quantitative angiography). Coronary flow reserve was calculated as the ratio of hyperemic to basal mean flow velocity. FFRmyo was calculated during maximal hyperemia as equal to 1-(hyperemic gradient [mean aortic pressure-5]), where 5 is the assumed central venous pressure. Positive and negative predictive values and predictive accuracy for reversible stress myocardial perfusion abnormalities were computed. There was a significant correlation between pressure-derived FFRmyo and distal coronary flow reserve (r = 0.46; p < 0.0001). The strongest predictor of stress myocardial perfusion imaging results was the poststenotic coronary flow reserve (chi square = 33.2; p < 0.0001). The correlation between stress myocardial perfusion imaging and FFRmyo was also significant (chi square = 8.3; p < 0.005). There was no correlation between stress myocardial perfusion imaging and percentage diameter stenosis (chi square = 2.9; p = 0.10) or minimal lumen diameter (chi square = 0.47; p = 0.73). A poststenotic coronary flow reserve of < or = 2 had a positive predictive value of 89% for regionally abnormal myocardial perfusion imaging abnormalities, whereas the positive predictive values of FFRmyo and angiographic percentage diameter stenosis were only 71% and 67% respectively. In conclusion, the predictive value of poststenotic coronary flow velocity reserve for stress-induced myocardial perfusion abnormalities exceeds that of the translesional FFRmyo. These findings should be considered when applying these techniques for clinical decision making in the assessment of coronary stenosis severity.

Heterogeneity of Coronary Flow Reserve in the Examination of Multiple Individual Allograft Coronary Arteries

BACKGROUND Epicardial and resistance vessel function in the transplanted heart has been evaluated primarily in regions supplied by a single vessel. Heterogeneity of flow among multiple perfusion fields as a marker of early endothelial dysfunction in the microcirculation has not been evaluated previously. This study tested the hypothesis that increased variability of coronary flow reserve (CFR) among multiple vascular regions would be associated with allograft coronary vasculopathy. METHODS AND RESULTS One hundred six posttransplant patients undergoing cardiac catheterization had measurement of CFR in at least 3 major epicardial vessels. Patients were divided into those with minimal angiographic abnormalities (n=37) and those with no angiographic abnormalities (n=69). The ranges, coefficients of variation, and univariate and multivariate regression analyses of CFR were computed to determine the major clinical factors influencing the degree of variability. The abnormal angiographic group was older (54+/-11 versus 47+/-13 years; P<0.003), had older hearts (35+/-11 versus 27+/-10 years; P<0.005), and were further posttransplant (1626+/-1022 versus 931+/-984 days; P<0.0009). There was no difference in global CFR between groups (normal, 3.4+/-0.8 versus abnormal, 3.4+/-0.7; P=NS). The coefficient of variation of CFR was higher for the abnormal group (16.3+/-8.6% versus 11.0+/-5.5%; P<0. 0006). Univariate and multivariate predictors of increased variability in CFR included angiographic abnormalities, patient age, and body mass index. Both angiographic abnormalities and an elevated CV of CFR were predictive of a combined end point of death, congestive heart failure, or subsequent development of >/=50% coronary stenosis. CONCLUSIONS These data demonstrate that increased variability of CFR is associated with discernible allograft coronary arteriopathy and is predictive of outcome in patients after heart transplantation.

Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease.

The functional significance of coronary stenoses is frequently determined by adjunctive noninvasive myocardial perfusion imaging. Poststenotic coronary flow velocity and pressure can be measured directly during routine cardiac catheterization. The aim of this study was to correlate poststenotic (distal) flow velocity and pressure with stress perfusion imaging in patients. Quantitative angiography, basal and hyperemic transstenotic coronary flow velocities, and pressure gradients were measured in 50 patients within 1 week of exercise (n = 29) or of pharmacologic (n = 21) stress perfusion imaging. Twenty-two of 25 patients (88%) with reversible perfusion abnormalities had diminished distal coronary flow velocity reserves (CFVR) of < or = 2.0 x baseline, whereas 22 of 25 (88%) with normal perfusion imaging studies had a normal distal CFVR of > 2.0 (p = 0.000 1). Thirteen of 25 patients (52%) with reversible perfusion abnormalities had transstenotic gradients > or = 20 mm Hg, whereas 20 of 25 (80%) with normal perfusion studies had gradients <20 mm Hg (p = 0.01). Quantitative angiography did not differentiate patients with normal versus abnormal myocardial perfusion imaging. Distal CFVR was correlated more significantly with myocardial perfusion imaging results (kappa = 0.76) than with pressure gradients (kappa = 0.32). Exercise and pharmacologic stress myocardial perfusion imaging abnormalities reflect diminished post-stenotic coronary flow to a greater degree than transstenotic pressure gradients.