Michalis Hamilos

Long-Term Clinical Outcome After Fractional Flow Reserve–Guided Treatment in Patients With Angiographically Equivocal Left Main Coronary Artery Stenosis

Background— Significant left main coronary artery stenosis is an accepted indication for surgical revascularization. The potential of angiography to evaluate the hemodynamic severity of a stenosis is limited. The aims of the present study were to assess the long-term clinical outcome of patients with an angiographically equivocal left main coronary artery stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR) and to determine the relationship between quantitative coronary angiography and FFR. Methods and Results— In 213 patients with an angiographically equivocal left main coronary artery stenosis, FFR measurements and quantitative coronary angiography were performed. When FFR was ≥0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; n=138). When FFR was <0.80, coronary artery bypass grafting was performed (surgical group; n=75). The 5-year survival estimates were 89.8% in the nonsurgical group and 85.4% in the surgical group (P=0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (P=0.50). Percent diameter stenosis at quantitative coronary angiography correlated significantly with FFR (r=−0.38, P<0.001), but a very large scatter was observed. In 23% of patients with a diameter stenosis <50%, the left main coronary artery stenosis was hemodynamically significant by FFR. Conclusions— In patients with equivocal stenosis of the left main coronary artery, angiography alone does not allow appropriate individual decision making about the need for revascularization and often underestimates the functional significance of the stenosis. The favorable outcome of an FFR-guided strategy suggests that FFR should be assessed in such patients before a decision is made “blindly” about the need for revascularization.

Prognostic Value of Fractional Flow Reserve: Linking Physiologic Severity to Clinical Outcomes

BACKGROUND Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

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.

Differential Effects of Drug-Eluting Stents on Local Endothelium-Dependent Coronary Vasomotion

OBJECTIVES The aim of our study was to compare coronary vasomotion after implantation of a second-generation biolimus A9-eluting stent (BES) and of a sirolimus-eluting stent (SES). BACKGROUND Drug-eluting stents (DES) have been associated with impaired local coronary vasomotion, delayed endothelialization, and increased late thrombotic risk. New DES with different drugs, pharmacokinetics, and polymers have been developed. METHODS Nineteen patients with a BES and 15 patients with a SES were studied 9 months after stent implantation. Endothelium-dependent and -independent coronary vasomotion were tested proximally and distally to the stent as well as at a reference segment during right atrial pacing at increasing heart rates. Quantitative coronary angiographic measurements were performed offline. RESULTS Of the patients with BES, 2 showed vasoconstriction with increased heart rate and 17 showed vasodilatation. Of the patients with a SES, 9 showed vasoconstriction while 6 showed vasodilatation. The SES showed significant vasoconstriction at both the proximal (-2.3 +/- 10% vs. 7.9 +/- 10%) and the distal (-5.4 +/- 9% vs. 6.1 +/- 8%) segments to the stent compared with the BES (p = 0.003 for proximal, p < 0.001 for distal segment). Endothelium-independent vasomotion after intracoronary nitrates did not differ significantly between the 2 groups (p = NS for proximal and distal segment). CONCLUSIONS Unlike the case with the SES, endothelium-dependent vasomotion at adjacent stent segments seems to be preserved after BES implantation. This result may be explained by the different drug release kinetics, DES design, or characteristics of polymer used in the stent system.

Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses

AIMS The present analysis addresses the potential clinical and physiologic significance of discordance in severity of coronary artery disease between the angiogram and fractional flow reserve (FFR) in a large and unselected patient population. METHODS AND RESULTS Between September 1999 and December 2011, FFR and percent diameter stenosis (DS) as assessed by quantitative coronary angiography were obtained in 2986 patients (n = 4086 coronary stenoses), in whom at least one stenosis was of intermediate angiographic severity. Fractional flow reserve correlated slightly but significantly with DS [-0.38 (95% CI: -0.41; -0.36); P < 0.001]. The sensitivity, specificity, and diagnostic accuracy of a ≥ 50% DS for predicting FFR ≤ 0.80 were 61% (95% CI: 59; 63), 67% (95% CI: 65; 69), and 0.64 (95% CI: 0.56; 0.72), respectively. In different anatomical settings, sensitivity and specificity showed marked variations between 35 to 74% and 58 to 76%, respectively, resulting in a discordance in 35% of all cases for these thresholds. For an angiographic threshold of 70% DS, the diagnostic performance by the Youdens index decreased from 0.28 to 0.11 for the overall population. CONCLUSION The data confirm that one-third of a large patient population shows discordance between angiogram ≥ 50%DS and FFR ≤ 0.8 thresholds of stenosis severity. Left main stenoses are often underestimated by the classical 50% DS cut-off compared with FFR. This discordance offers physiologic insights for future trials. It is hypothesized that the discordance between angiography and FFR is related to technical limitations, such as imprecise luminal border detection by angiography, as well as to physiologic factors, such as variable minimal microvascular resistance.

On the Inappropriateness of Noninvasive Multidetector Computed Tomography Coronary Angiography to Trigger Coronary Revascularization: A Comparison With Invasive Angiography

OBJECTIVES Our purpose was to evaluate the appropriateness of multidetector computed tomography angiography (MDCTA) as an anatomical standard for decision making in patients with known or suspected coronary artery disease. BACKGROUND Although correlative studies between MDCTA and coronary angiography (CA) show good agreement, MDCTA visualizes plaque burden and calcifications well before luminal dimensions are encroached. METHODS Pressure-derived fractional flow reserve (FFR) was obtained in 81 patients (116 vessels) who underwent both CA and MDCTA. Segments were visually graded for stenosis severity as: G0 = normal, G1 = nonobstructive (<50% diameter reduction), and G2 = obstructive (> or =50% diameter reduction). RESULTS Concordance between segmental severity scores by MDCTA and CA was good (k = 0.74; 95% confidence interval: 0.56 to 0.92). Diagnostic performance of MDCTA for detection of functionally significant stenosis based on FFR was low (sensitivity 79%; specificity 64%; positive likelihood ratio 2.2; negative likelihood ratio 0.3). Revascularization was considered appropriate in the presence of reduced FFR (< or =0.75). Decision making based on MDCTA guidance would result in revascularization in the absence of ischemia in 22% of patients (18 of 81) and inappropriate deferral in 7% (6 of 81), while revascularization in the absence of ischemia would be 16% (13 of 81) and inappropriate deferral 12% (10 of 81) with decisions guided by CA. Combined evaluation of stenosis severity using both anatomy (with either CA or MDCTA) and function (with FFR) yields the highest proportion of appropriate decisions: 90% and 91%, respectively (p = 0.0001 vs. CA only, p = 0.0001 vs. MDCTA only). CONCLUSIONS Similar to CA, anatomical assessment of coronary stenosis severity by MDCTA does not reliably predict its functional significance.

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.

Interference of Drug-Eluting Stents With Endothelium-Dependent Coronary Vasomotion Evidence for Device-Specific Responses

Background—There is evidence that endothelial coverage of drug-eluting stents might be delayed or absent, a risk factor for late thrombotic events. We studied the effects of different drug-polymer-device iterations on endothelium-dependent coronary vasomotion. Systemic markers of endothelial inflammation were correlated with coronary vasomotor changes. Methods and Results—Patients with paclitaxel-eluting stents (n=11), sirolimus-eluting stents (n=21), biolimus A9-eluting stents (n=28), zotarolimus-eluting stents (n=10), and bare-metal stents (n=13) were studied 10, 9, 9, 9, and 12 months after implantation, respectively. Endothelium-dependent coronary vasomotion was tested proximally and distally to the stent and at a reference vessel segment during atrial pacing at increasing heart rates by quantitative coronary angiography. Indexes of platelet-monocyte binding and other biomarkers were studied in a subgroup of 19 patients. The baseline characteristics and hemodynamics of the patients in the different stent groups were comparable. Significant differences were observed across the 5 stent groups, concerning the vasomotion of segments proximal (P=0.006) and distal (P=0.003) to the stent. Normal vasomotion (vasodilatation) was maintained in the biolimus A9-eluting stent, zotarolimus-eluting stent, and bare-metal stent groups, whereas vasoconstriction was observed in the sirolimus-eluting stent and paclitaxel-eluting stent groups. Platelet-monocyte binding in whole blood showed a significant inverse correlation with vasomotion in reference but not in segments adjacent to the stent (r=−0.57; P=0.01). Conclusions—Paclitaxel-eluting stents and sirolimus-eluting stents seem to cause endothelial dysfunction of the implanted vessel, whereas biolimus A9-eluting stents and zotarolimus-eluting stents behave more closely to bare-metal stents, with preserved endothelial vasomotor response. Coronary vasoconstriction was not associated with detectable systemic endothelial activation.

Direct stenting for stable angina pectoris is associated with reduced periprocedural microcirculatory injury compared with stenting after pre-dilation.

OBJECTIVES We conducted a randomized study to compare the effect of direct stenting (DS) and conventional stenting (CS) on post-procedural index of microcirculatory resistance (IMR) values. BACKGROUND Direct stenting has been suggested to reduce periprocedural microcirculatory injury compared with stenting that follows pre-dilation (CS). The index of microcirculatory resistance is a sensitive invasive marker of coronary microvascular resistance. METHODS Fifty patients admitted for elective percutaneous coronary intervention (PCI) were included. All patients had stable angina (Canadian Cardiovascular Society class <IV) related to a lesion suitable for DS and were randomized to DS (n = 25) or CS (n = 25). Baseline demographics and clinical and procedural data were comparable in both groups. An intracoronary pressure/temperature sensor-tipped guide wire was used. Thermodilution curves were obtained at baseline and during maximal hyperemia achieved by infusion of intravenous adenosine. The index of microcirculatory resistance was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time. RESULTS After otherwise-uneventful PCI, patients treated with CS had significantly greater IMR (DS 13 +/- 3, CS 24 +/- 14; p < 0.01) and tended to have greater post-PCI troponin T values (DS 0.035 +/- 0.04, CS 0.17 +/- 0.02; p = 0.07). In the whole sample, 20% of patients had post-PCI troponin release (troponin T >0.03 ng/ml). Patients with troponin elevation had significantly greater post-PCI IMR values than patients without troponin elevation: 24.7 +/- 13.2 versus 16.9 +/- 10.2; p = 0.04. CONCLUSIONS In patients undergoing successful coronary stenting for stable angina, DS is associated with reduced microvascular dysfunction induced by PCI as compared with CS.

In-hospital switching of oral P2Y12 inhibitor treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention: Prevalence, predictors and short-term outcome

BACKGROUND P2Y12 inhibitor switching has appeared in clinical practice as a consequence of prasugrel and ticagrelor availability, apart from clopidogrel, for use in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS In the context of the GReek AntiPlatelet REgistry (GRAPE) we assessed the prevalence, predictive factors and short-term outcome of in-hospital P2Y12 inhibitor switching in 1794 ACS patients undergoing PCI. RESULTS Switching occurred in 636 (35.5%) patients of which in the form of clopidogrel to a novel agent, novel agent to clopidogrel and between prasugrel and ticagrelor in 574 (90.4%), 34 (5.3%) and 27 (4.3%) patients, respectively. Presentation to non PCI-capable hospital, bivalirudin use, age ≥75 years (inverse predictor), and regional trends emerged as predictive factors of switching to a novel agent. At combined in-hospital and one-month follow-up, propensity matched pairs analysis showed no differences in major adverse cardiovascular (MACE) or bleeding events between switching from clopidogrel to a novel agent vs novel agent constant administration. More Bleeding Academic Research Consortium type 1, type 2 and any type events and fewer MACE were seen when switching from clopidogrel to a novel agent vs only clopidogrel administration (23.7%, 3.8%, 30.6%, 1.2% vs 8.9%, 1.2%, 12.0%, 3.8% with P < .001, P = .03, P < .001 and P = .03 respectively). CONCLUSIONS In a real-life experience with contemporary antiplatelet treatment in ACS patients undergoing PCI, in-hospital switching represents common clinical practice. Clinical factors and regional practice differences seem to affect this strategys choice, while switching to a novel agent may be associated with higher risk of bleeding.