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Fractional Flow Reserve for the Assessment of Nonculprit Coronary Artery Stenoses in Patients With Acute Myocardial Infarction

OBJECTIVES We investigated the reliability of fractional flow reserve (FFR) of nonculprit coronary stenoses during percutaneous coronary intervention (PCI) in acute myocardial infarction. BACKGROUND Assessing the hemodynamic severity of the nonculprit coronary artery stenoses at the acute phase of a myocardial infarction could improve risk stratification and shorten the diagnostic work-up. METHODS One hundred one patients undergoing PCI for an acute myocardial infarction (n = 75 with ST-segment elevation myocardial infarction [STEMI], and n = 26 with non-ST-segment elevation myocardial infarction) were prospectively recruited. The FFR measurements in 112 nonculprit stenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later. In addition, left ventricular ejection fraction, quantitative coronary angiographic measurements of the nonculprit stenoses, Thrombolysis In Myocardial Infarction (TIMI) flow, corrected TIMI frame count (cTFC), and the index of microcirculatory resistance (n = 14) of the nonculprit vessels were assessed in the acute phase and at control angiogram. RESULTS The FFR value of the nonculprit stenoses did not change between the acute and follow-up (0.77 ± 0.13 vs. 0.77 ± 0.13, respectively, p = NS). In only 2 patients, the FFR value was higher than 0.8 at the acute phase and lower than 0.75 at follow-up. The TIMI flow, cTFC, percentage diameter stenosis, minimum lumen diameter, and index of microcirculatory resistance did not change. Left ventricular ejection fraction increased significantly in patients with STEMI (from 54 ± 13% to 57 ± 13%, p = 0.03). CONCLUSIONS During the acute phase of acute coronary syndromes, the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR. This allows a decision about the need for additional revascularization and might contribute to a better risk stratification.

Translesional Pressure Gradients to Predict Blood Pressure Response After Renal Artery Stenting in Patients With Renovascular Hypertension

Background—In previous studies on the effect of renal stenting on arterial hypertension, patients were selected mainly on the basis of angiographic parameters of the renal artery stenosis. The aim of the present study was to evaluate whether translesional pressure gradients could identify the patients with renal artery stenosis who might benefit from stenting. Methods and Results—A total of 53 consecutive hypertensive patients with unilateral RAS scheduled for renal artery intervention were recruited. Transstenotic pressure gradients were measured at baseline and during maximal hyperemia, before renal artery stenting. Twenty-four-hour ambulatory blood pressure measurements were performed in all patients before and 3 months after the intervention. Average reductions in systolic blood pressure and diastolic blood pressure at follow-up were −20±30 mm Hg and −2±12 mm Hg, respectively. At multivariate analysis, dopamine-induced mean gradient was the only independent predictor of the variations of both systolic blood pressure (regression coefficient=−4.03, standard error=1.11; P<0.001) and diastolic blood pressure (regression coefficient=−3.11, standard error=1.20; P=0.009). Patients who showed a decline in systolic blood pressure from the baseline value >20 mm Hg were considered as “responders.” The optimal cutoff for identification of “responders” was a dopamine-induced mean gradient ≥20 mm Hg (area under the curve, 0.77; 95% confidence interval, 0.64 to 0.90; P=0.001). Conclusions—A dopamine-induced mean pressure gradient of ≥20 mm Hg is highly predictive of arterial hypertension improvement after renal stenting, and therefore this measurement is useful for appropriate selection of patients with arterial hypertension.

Long-term follow-up after fractional flow reserve-guided treatment strategy in patients with an isolated proximal left anterior descending coronary artery stenosis

OBJECTIVES This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR). BACKGROUND When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized. METHODS In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was ≥ 0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population. RESULTS The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 ± 14% vs. 54 ± 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001). CONCLUSIONS Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR ≥ 0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population.

High residual platelet reactivity after clopidogrel: extent of coronary atherosclerosis and periprocedural myocardial infarction in patients with stable angina undergoing percutaneous coronary intervention.

OBJECTIVES We tested the hypothesis that residual platelet reactivity after clopidogrel correlates with the extent and severity of coronary atherosclerosis in patients undergoing elective percutaneous coronary intervention (PCI). BACKGROUND Platelets are actively involved in vascular atherosclerosis. METHODS We prospectively enrolled 338 patients undergoing PCI for stable angina, loaded with 600-mg clopidogrel. Platelet reactivity was assessed 12 h later by measuring P2Y12 reactivity unit (PRU) with VerifyNow P2Y12 assay (Accumetrics, San Diego, California). High platelet reactivity (HPR) was defined as PRU value >or=240. Presence of multivessel disease (MVD) and total stent length (TSL) were used as surrogate markers of atherosclerosis severity and extension. RESULTS Patients with MVD showed higher PRU compared with single-vessel disease (SVD) patients (222 +/- 85 vs. 191 +/- 73; p < 0.001). The PRU increased with the number of stenotic coronaries (1-vessel disease: 191 +/- 73; 2-vessel disease: 220 +/- 88; 3-vessel disease: 226 +/- 80; p = 0.002). The PRU was higher in the third TSL tertile compared with first tertile (217 +/- 83 vs. 191 +/- 73; p = 0.048). The HPR was most frequently observed among MVD patients (40.5% vs. 21.6% in patients with SVD, respectively; p < 0.001) and those in the third TSL tertile (35.8% vs. 22.2% first tertile; p = 0.028). Higher incidence of periprocedural myocardial infarction was observed in patients with HPR (41.2% vs. 26.7% in patients without HPR; p = 0.008) and in those in the third tertile TSL (37.7% vs. 23.1% first tertile; p = 0.020). By multivariate analysis, HPR was the only independent predictor of periprocedural myocardial infarction (p = 0.034). CONCLUSIONS Patients with more extensive coronary atherosclerosis have a higher rate of HPR, which might partly account for higher risk of periprocedural MI.

Comparison of 600 Versus 300-mg Clopidogrel Loading Dose in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Coronary Angioplasty

The aim of the present study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention (PCI). Two hundred fifty-five consecutive patients presenting with ST-segment elevation myocardial infarctions who underwent primary PCI were enrolled. Patients were divided into 2 groups on the basis of the loading dose of clopidogrel received before the procedure (600 vs 300 mg). Procedural angiographic end points and 1-year major adverse cardiac events were compared between the 2 groups. Major adverse cardiac events were defined as death, nonfatal myocardial infarction, and target vessel revascularization. There were no significant differences in baseline clinical and angiographic features between the 2 groups: 157 (62%) in the clopidogrel 600 mg group and 98 (38%) in the 300 mg group. Patients receiving 600-mg loading dose of clopidogrel showed a significantly lower incidence of post-PCI myocardial blush grade 0 or 1 (odds ratio 0.64, 95% confidence interval 0.43 to 0.96, p = 0.03) and significantly less common no-reflow phenomenon (odds ratio 0.38, 95% confidence interval 0.15 to 0.98, p = 0.04) compared to those in the 300-mg group. Propensity-adjusted Cox analysis showed significantly higher survival free of major adverse cardiac events in patients receiving 600-mg loading dose of clopidogrel compared to those receiving the lower dose (hazard ratio 0.57, 95% confidence interval 0.33 to 0.98, p = 0.04). In conclusion, a 600-mg loading dose of clopidogrel is associated with improvements in procedural angiographic end points and 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction who undergo primary PCI compared to a 300-mg dose.

Circadian variations of ischemic burden among patients with myocardial infarction undergoing primary percutaneous coronary intervention

BACKGROUND Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms. Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59). RESULTS There was no difference between the groups regarding baseline patients and managements characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P < .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P < .05). CONCLUSION This study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction.

Effective radiation dose, time, and contrast medium to measure fractional flow reserve.

OBJECTIVES This study sought to define the additional effective radiation dose, procedural time, and contrast medium needed to obtain fractional flow reserve (FFR) measurements after a diagnostic coronary angiogram. BACKGROUND The FFR measurements performed at the end of a diagnostic angiogram allow the obtaining of functional information that complements the anatomic findings. METHODS In 200 patients (mean age 66 +/- 10 years) undergoing diagnostic coronary angiography, FFR was measured in at least 1 intermediate coronary artery stenosis. Hyperemia was achieved by intracoronary (n = 180) or intravenous (n = 20) adenosine. The radiation dose (mSv), procedural time (min), and contrast medium (ml) needed for diagnostic angiography and FFR were recorded. RESULTS A total of 296 stenoses (1.5 +/- 0.7 stenoses per patient) were assessed. The additional mean radiation dose, procedural time, and contrast medium needed to obtain FFR expressed as a percentage of the entire procedure were 30 +/- 16% (median 4 mSv, range 2.4 to 6.7 mSv), 26 +/- 13% (median 9 min, range 7 to 13 min), and 31 +/- 16% (median 50 ml, range 30 to 90 ml), respectively. The radiation dose and contrast medium during FFR were similar after intravenous and intracoronary adenosine, though the procedural time was slightly longer with intravenous adenosine (median 11 min, range 10 to 17 min, p = 0.04) than with intracoronary adenosine (median 9 min, range 7 to 13 min). When FFR was measured in 3 or more lesions, radiation dose, procedural time, and contrast medium increased. CONCLUSIONS The additional radiation dose, procedural time, and contrast medium to obtain FFR measurement are low as compared to other cardiovascular imaging modalities. Therefore, the combination of diagnostic angiography and FFR measurements is warranted to provide simultaneously anatomic and functional information in patients with coronary artery disease.

Thrombus aspiration in primary percutaneous coronary intervention in high‐risk patients with ST‐elevation myocardial infarction: A real‐world registry

Objectives: To evaluate the effect of thrombus aspiration in a real‐world all‐comer patient population with STEMI undergoing primary PCI. Background: Catheter thrombus aspiration in primary PCI was beneficial in randomized clinical trials. Methods: We enrolled 313 STEMI patients presenting with TIMI Flow Grade 0 or 1 in the infarct related artery at baseline angiogram undergoing primary PCI. Patients were divided in two groups based on whether thrombus aspiration was attempted. This decision was left at operators discretion. Procedural and long‐term clinical outcomes were compared between the two groups. Results: Baseline characteristics were similar between groups: 194 (62%) received thrombus aspiration and 119 underwent conventional PCI. Thrombus aspiration was associated with significantly lower post‐PCI TIMI Frame Count values (19 ± 15 vs. 25 ± 17; P = 0.002) and higher TIMI Flow Grade 3 (92% vs. 73%; P < 0.001). Postprocedural myocardial perfusion assessed by myocardial blush grade (MBG) was significantly increased in the thrombus aspiration group (MBG 3: 44% vs. 21%; P < 0.001). No significant difference was found between the two groups in clinical outcome at 30 days. At one year, patients treated with thrombus aspiration showed significantly higher overall survival (HR 0.41, 95% CI 0.20–0.81; log‐rank P = 0.010) and MACE‐free survival (HR 0.49, 95% CI 0.28–0.85; log‐rank P = 0.011). Conclusions: In real‐world all‐comer STEMI patients with occluded infarct‐related artery, thrombus aspiration prior to PCI improves coronary flow, myocardial perfusion, and long‐term clinical outcome as compared with PCI in the absence of thrombus aspiration.

Pressure–Diameter Relationship in Human Coronary Arteries

Background—To quantify the changes in arterial dimensions after the acute changes in pressure associated with percutaneous coronary intervention (PCI). Methods and Results—Forty-eight patients with one angiographically moderate-to-severe stenosis were included in the study. The pressure proximal and distal to the stenosis and the arterial diameter proximal and distal to the stenosis were measured at baseline, after intracoronary nitrates, and after stent PCI. In addition, in 8 patients distal pressure and coronary diameter were assessed while graded, controlled stenoses were created in the stented segment by progressive inflation of a balloon catheter. The mean diameter of the proximal coronary segment was 2.75±0.08 mm, 2.92±0.08 mm (+7.4%), and 3.10±0.07 mm (+14.7%) at baseline, after nitrates and after PCI, respectively (P<0.001). The mean diameter of the distal coronary segment was 2.07±0.09 mm, 2.23±0.09 mm (+9.7%), and 2.5±0.07 mm (+28.4%) at baseline, after nitrates and after PCI, respectively (P<0.001). The increase in distal diameter correlated significantly with the increase in distal pressure after PCI (r2=0.57; P<0.001). When graded stenoses were created, a decrease in diameter of 18±4% was observed with a pressure drop of 43±5 mm Hg. Conclusions—The diameter of coronary arteries markedly varies with their distending pressure. After re-establishment of a normal distending pressure by stenting of severe coronary stenoses, a proportional increase in vessel diameter is observed. This should be taken into account when choosing the stent diameter and is an argument to discourage direct stenting.

Transcriptional fingerprint of human whole blood at the site of coronary occlusion in acute myocardial infarction

AIMS Transcriptome patterns associated with acute myocardial infarction at the site of coronary occlusion are largely unknown. The aim of this study was to decipher the angiogenic, atherosclerotic, and inflammatory mRNA profiles in whole blood samples collected at the site of coronary occlusion in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS In five consecutive patients with STEMI, blood was sampled at the site of occlusion (local) and in the systemic circulation (peripheral) during primary percutaneous coronary intervention. RNA was extracted from whole blood samples. Among 221 genes involved in angiogenesis, inflammation and atherosclerosis, 24 were shown to be differentially modulated locally, by analysis with custom-designed DNA array technology. Validation in 28 distinct STEMI patients using real-time quantitative PCR identified seven out of these 24 genes to be consistently and significantly upregulated in local versus peripheral blood (p<0.05). Three genes were chemokine family members (CCL2, CCL18 and CXCL12), three genes belonged to the cell-cell and cell-extracellular matrix family (FN1, CDH5 and SPP1), and one gene was representative of the lipoprotein family (APOE). CONCLUSIONS We identified a set of whole blood transcripts induced at the site of coronary occlusion in the acute phase of myocardial infarction. Resolved genes indicate a predominant role for chemokines, cell-extracellular matrix, and lipoprotein alterations in the pathophysiology of acute myocardial infarction and the initial response to myocardial injury.