Kathinka Peels

Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses

BACKGROUND The clinical significance of coronary-artery stenoses of moderate severity can be difficult to determine. Myocardial fractional flow reserve (FFR) is a new index of the functional severity of coronary stenoses that is calculated from pressure measurements made during coronary arteriography. We compared this index with the results of noninvasive tests commonly used to detect myocardial ischemia, to determine the usefulness of the index. METHODS In 45 consecutive patients with moderate coronary stenosis and chest pain of uncertain origin, we performed bicycle exercise testing, thallium scintigraphy, stress echocardiography with dobutamine, and quantitative coronary arteriography and compared the results with measurements of FFR. RESULTS In all 21 patients with an FFR of less than 0.75, reversible myocardial ischemia was demonstrated unequivocally on at least one noninvasive test. After coronary angioplasty or bypass surgery was performed, all the positive test results reverted to normal. In contrast, 21 of the 24 patients with an FFR of 0.75 or higher tested negative for reversible myocardial ischemia on all the noninvasive tests. No revascularization procedures were performed in these patients, and none were required during 14 months of follow-up. The sensitivity of FFR in the identification of reversible ischemia was 88 percent, the specificity 100 percent, the positive predictive value 100 percent, the negative predictive value 88 percent, and the accuracy 93 percent. CONCLUSIONS In patients with coronary stenosis of moderate severity, FFR appears to be a useful index of the functional severity of the stenoses and the need for coronary revascularization.

Fractional Flow Reserve A Useful Index to Evaluate the Influence of an Epicardial Coronary Stenosis on Myocardial Blood Flow

BACKGROUND Fractional flow reserve (FFR), defined as the ratio of maximum flow in the presence of a stenosis to normal maximum flow, is a lesion-specific index of stenosis severity that can be calculated by simultaneous measurement of mean arterial, distal coronary, and central venous pressure (Pa, Pd, and Pv, respectively), during pharmacological vasodilation. The aims of this study were to define ranges of FFR values, whether associated with inducible ischemia or not, and to investigate FFR in normal coronary arteries. METHODS AND RESULTS In 60 patients accepted for percutaneous transluminal coronary angioplasty (PTCA) of single-vessel disease, with a positive exercise test (ET) < 24 hours before PTCA, FFR was determined during adenosine-induced hyperemia just before and 15 minutes after angioplasty. Pa was measured by the guiding catheter, Pd by an 0.018-in fiber-optic pressure-monitoring wire, and Pv, by a multipurpose catheter. The ET was repeated after 5 to 7 days, and only if this second ET had reverted to normal was the pre-PTCA value of FFR definitely considered to be associated with inducible ischemia and the post-PTCA value not. Myocardial FFR (FFRmyo) increased from 0.53 +/- 0.15 before PTCA to 0.88 +/- 0.07 after PTCA. Coronary FFR increased from 0.38 +/- 0.19 to 0.83 +/- 0.12. In all patients, values of FFRmyo definitely associated with ischemia were < or = 0.74, whereas all except two values not associated with inducible ischemia exceeded 0.74. Moreover, FFRmyo in 18 coronary arteries in 5 normal patients equaled 0.98 +/- 0.03. CONCLUSIONS A value of FFRmyo of 0.74 reliably discriminates coronary stenosis, whether associated with inducible ischemia or not. Therefore, FFRmyo is a useful index to determine the functional significance of an epicardial coronary stenosis and may facilitate clinical decision making in patients with an equivocal coronary stenosis.

Long-Term Follow-Up After Deferral of Percutaneous Transluminal Coronary Angioplasty of Intermediate Stenosis on the Basis of Coronary Pressure Measurement

OBJECTIVES This study sought to determine the safety of deferral of percutaneous transluminal coronary angioplasty (PTCA) of angiographically intermediate but functionally nonsignificant stenosis, as assessed by coronary pressure measurement and myocardial fractional flow reserve (FFRmyo). BACKGROUND Decision making in patients with chest pain and intermediate coronary stenosis remains difficult. In these cases it is unclear whether the risk of an intervention and the potentially subsequent restenosis outweigh the future risk of an event if the lesion remains untreated. FFRmyo is a lesion-specific functional index of epicardial stenosis severity that accurately distinguishes stenoses associated with inducible ischemia. METHODS Retrospective analysis and follow-up was performed in 100 consecutive patients referred to our centers for PTCA of an intermediate stenosis but in whom the planned intervention was deferred on the basis of an FFRmyo > or = 0.75. RESULTS During a follow-up period of 18+/-13 months (mean +/- SD, range 3 to 42), two patients died of noncardiac causes. Ninety patients remained free of any coronary events, and their average Canadian Cardiovascular Society class decreased from 2.0+/-1.2 at baseline to 0.7+/-0.9 at follow-up (p < 0.0001). A coronary event occurred in eight patients and was target-vessel related in four. CONCLUSIONS In patients with chest pain referred for PTCA of an intermediate stenosis, deferral of the intervention on the basis of an FFRmyo > or = 0.75 is safe and is associated with a much lower clinical event rate than if the procedure had been performed as initially planned in these patients.

Fractional Flow Reserve

The potential benefit of revascularization depends on the presence and extent of myocardial ischemia. Performing percutaneous coronary intervention (PCI) on ischemia-inducing coronary stenoses improves both symptoms and outcome, while performing PCI on non-ischemia-inducing stenoses has no benefit and is potentially harmful. Noninvasive testing and the coronary angiogram have limited ability to distinguish specific ischemic territories and responsible stenoses, especially in multivessel coronary disease. To overcome these shortcomings, fractional flow reserve (FFR) has been developed as a stenosis-specific index to determine whether a coronary stenosis has ischemic potential. FFR-guided PCI improves both symptoms and outcome. As such, knowledge of coronary physiology and FFR has become imperative in daily coronary decision making.

Value of fractional flow reserve in making decisions about bypass surgery for equivocal left main coronary artery disease

OBJECTIVE To investigate the value of coronary pressure derived fractional flow reserve (FFR) measurements in supporting decisions about medical or surgical treatment in patients with angiographically equivocal left main coronary artery stenosis. DESIGN A two centre prospective single cohort follow up study. INTERVENTIONS FFR of the left main coronary artery was determined in 54 consecutive patients with angiographically equivocal left main coronary artery disease. If FFR was ⩾ 0.75, medical treatment was chosen; if FFR was < 0.75, surgical treatment was chosen. MAIN OUTCOME MEASURES Freedom from death, myocardial infarction, or any coronary revascularisation procedure. RESULTS In 24 patients (44%), FFR was ⩾ 0.75 and medical treatment was chosen (medical group). In the remaining 30 patients (56%), FFR was < 0.75 and bypass surgery was performed (surgical group). Mean (SD) follow up was 29 (15) months (range 12–65 months). Survival among patients at three years of follow up was 100% in the medical group and 97% in the surgical group. Event-free survival was 76% in the medical group and 83% in the surgical group. CONCLUSIONS FFR supports decision making in equivocal left main coronary artery disease. If FFR is below 0.75, the decision for bypass surgery is supported. If FFR is above 0.75, a conservative approach is justified.

Usefulness of Fractional Flow Reserve to Predict Clinical Outcome After Balloon Angioplasty

BACKGROUND After regular coronary balloon angioplasty, it would be helpful to identify those patients who have a low cardiac event rate. Coronary angiography alone is not sensitive enough for that purpose, but it has been suggested that the combination of optimal angiographic and optimal functional results indicates a low restenosis chance. Pressure-derived myocardial fractional flow reserve (FFR) is an index of the functional severity of the residual epicardial lesion and could be useful for that purpose. METHODS AND RESULTS In 60 consecutive patients with single-vessel disease, balloon angioplasty was performed by use of a pressure instead of a regular guide wire. Both quantitative coronary angiography (QCA) and measurement of FFR were performed 15 minutes after the procedure. A successful angioplasty result, defined as a residual diameter stenosis (DS) <50%, was achieved in 58 patients. In these patients, DS and FFR, measured 15 minutes after PTCA, were analyzed in relation to clinical outcome. In those 26 patients with both optimal angiographic (residual DS by QCA </=35%) and optimal functional (FFR >/=0.90) results, event-free survival rates at 6, 12, and 24 months were 92+/-5%, 92+/-5%, and 88+/-6%, respectively, versus 72+/-8%, 69+/-8%, and 59+/-9%, respectively, in the remaining 32 patients in whom the angiographic or functional result or both were suboptimal (P=0.047, P=0.028, and P=0.014, respectively). CONCLUSIONS In patients with a residual DS </=35% and FFR >/=0.90, clinical outcome up to 2 years is excellent. Therefore, there is a complementary value of coronary angiography and coronary pressure measurement in the evaluation of PTCA result.

Percutaneous coronary intervention or bypass surgery in multivessel disease? A tailored approach based on coronary pressure measurement

The optimal revascularization strategy, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG), for patients with multivessel coronary artery disease (MVD) remains controversial. The aim of the present study was to compare the long‐term outcomes after selective PCI of only hemodynamically significant lesions (fractional flow reserve, or FFR < 0.75) to CABG of all stenoses in patients with MVD. In 150 patients with MVD referred for CABG, FFR was determined in 381 coronary arteries considered for bypass grafting. If the FFR was less than 0.75 in three vessels or in two vessels including the proximal left anterior descending (LAD) artery, CABG was performed (CABG group). If only one or two vessels were physiologically significant (not including the proximal LAD), PCI of those lesions was performed (PCI group). Of the 150 patients, 87 fulfilled the criteria for CABG and 63 for PCI. There were no significant differences in the angiographic or other baseline characteristics between the two groups. At 2‐year follow‐up, no differences were seen in adverse events, including repeat revascularization (event‐free survival 74% in the CABG group and 72% in the PCI group). A similar number of patients were free from angina (84% in the CABG group and 82% in the PCI group). Importantly, the results in both groups were as good as the surgical groups in previous studies comparing PCI and CABG in MVD. In patients with multivessel disease, PCI in those with one or two hemodynamically significant lesions as identified by an FFR < 0.75 yields a similar favorable outcome as CABG in those with three or more culprit lesions despite a similar angiographic extent of disease. Catheter Cardiovasc Interv 2004;63:184–191.

Which patient benefits from early angiotensin-converting enzyme inhibition after myocardial infarction? Results of one-year serial echocardiographic follow-up from the captopril and thrombolysis study (CATS)

OBJECTIVES In this study we sought to investigate the effect of intervention with captopril within 6 h of the onset of myocardial infarction on left ventricular volume and clinical symptoms of heart failure in relation to infarct size during a 1-year follow-up period. BACKGROUND Remodeling of the heart starts in the early phase of myocardial infarction and is associated with an adverse prognosis. Angiotensin-converting enzyme inhibition started in the subacute or late phase after myocardial infarction has been shown to improve prognosis. METHODS In the Captopril and Thrombolysis Study, 298 patients with a first anterior myocardial infarction treated with intravenous streptokinase were randomized to receive either oral captopril (25 mg three times a day) or placebo. The left ventricular volume index was assessed by two-dimensional echocardiography within 24 h, on days 3, 10 and 90 and after 1 year. RESULTS A small but significant increase in left ventricular volume indexes was observed after 12 months. Using a random coefficient model, no significant treatment effect on left ventricular volumes could be detected. In contrast, when survival models were used, the occurrence of left ventricular dilation was significatnly lower in captopril-treated patients (p = 0.018). In addition, the incidence of heart failure was lower in the captopril group (p < 0.03). This effect appeared early and was most obvious in patients with a medium-sized infarct (p = 0.04) and was not present in large infarcts. CONCLUSIONS Very early treatment with captopril after myocardial infarction significantly reduces the occurrence of early dilation and the progression to heart failure. These data underscore the importance of early treatment. Furthermore, patients with intermediate infarct size benefit the most from this treatment strategy.

Left ventricular wall motion score as an early predictor of left ventricular dilation and mortality after first anterior infarction treated with thrombolysis

Abstract To recognize patients prone to subsequent left ventricular dilation after the acute phase of a myocardial infarction treated with thrombolysis, we studied 233 patients with a first anterior infarction, treated with thrombolysis, with 2-dimensional echocardiography within 12 hours after admission and 3 months later. A wall motion score index (WMSI) and left ventricular volumes were assessed, and enzymatic infarct size was expressed as cumulative alphahydroxybutyrate dehydrogenase determined in the first 72 hours after infarction. Patients who died (17 of 233, 7%) after a mean follow-up of 517 days had a significantly higher acute WMSI (2.1 ± 0.3, mean ± SD) than those who survived (1.9 ± 0.4) (p = 0.006). With use of this cutoff value of 2 for WMSI, ventricles with an acute WMSI ≤2 (62%) showed no increase in end-diastolic volume index (EDVI) or end-systolic volume index (ESVI), whereas ventricles with an acute WMSI >2 (38%) showed a significant increase in ESVI (6.1 ± 12.2 ml/m 2 ) and in EDVI (10.3 ± 16.6 ml/m 2 ) in the first 3 months. Using a cutoff value of 1,000 U/L for cumulative alphahydroxybutyrate dehydrogenase, only infarcts with a value of > 1,000 U/L (52%) caused a significant increase in EDVI (10.8 ± 14.3 ml/m 2 ) and ESVI (6.5 ± 10.0 ml/m 2 ) in the first 3 months. Thus, acutely assessed WMSI of >2 can readily predict subsequent dilation in patients with a first anterior infarction treated with streptokinase and is a good predictor of mortality. Enzymatic infarct size also is a good predictor of dilation, although not available until 3 days after infarction.

Association of Left Ventricular Remodeling and Nonuniform Electrical Recovery Expressed by Nondipolar QRST Integral Map Patterns in Survivors of a First Anterior Myocardial Infarction

BACKGROUND Progressive left ventricular dilatation after myocardial infarction is associated with a high mortality rate, the majority of which is arrhythmogenic in origin. The underlying mechanism of this relation remains unknown. It has been suggested, however, that left ventricular dilatation is accompanied by changes in repolarization characteristics that may facilitate the occurrence of life-threatening ventricular arrhythmias. METHODS AND RESULTS We examined 62-lead body surface QRST integral maps during sinus rhythm in 78 patients at 349 +/- 141 days after thrombolysis for a first anterior myocardial infarction. Visual map analysis was directed at discriminating dipolar (uniform repolarization) from nondipolar (nonuniform repolarization) patterns. In addition, the nondipolar content of each map was assessed quantitatively with the use of eigenvector analysis. Nondipolar map patterns were present in almost one third of the patients (32%). Left ventricular end-systolic and end-diastolic volumes were assessed echocardiographically before discharge and after 3 and 12 months with the use of the modified biplane Simpson rule. The increase in left ventricular end-systolic volume 1 year after myocardial infarction was more pronounced in patients with nondipolar QRST integral map patterns (14.47 +/- 14.10 versus 4.22 +/- 8.44 mL/m2, P = .017). In patients with an increase in end-systolic volume of more than 16 mL/m2 (upper quartile), the prevalence of nondipolar maps was 89% compared with 29% in patients with dilatation of less than 16 mL/m2. In addition, the nondipolar content of maps in patients in the upper quartile was significantly increased compared with the lower quartiles (49 +/- 14% versus 37 +/- 12%, P = .013). Logistic regression analysis revealed that an end-systolic volume of more than 42 mL/m2 after 1 year contributed independently to the appearance of nondipolar maps. Patients with high-grade ventricular arrhythmias showed a higher nondipolar content (49 +/- 17% versus 39 +/- 10%, P = .013). QTc dispersion did not discriminate between patients with and those without high-grade ventricular arrhythmias. Also, the association between left ventricular remodeling and nondipolar map patterns was confirmed prospectively in an additional group of 15 patients. CONCLUSIONS Nondipolar map patterns are present in 32% of patients after thrombolysis for a first anterior myocardial infarction and are associated with increased left ventricular dilatation. These data support the hypothesis that left ventricular dilatation after myocardial infarction leads to changes in repolarization characteristics that may facilitate the occurrence of life-threatening ventricular arrhythmias.