Fractional Flow Reserve to Guide Treatment of Patients With Multivessel Coronary Artery Disease.

BACKGROUND: There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. OBJECTIVES: The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. METHODS: The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. RESULTS: The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months' extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). CONCLUSIONS: In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555).

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

Diagnosis and Management of Spontaneously Recanalized Coronary Thrombus Guided by Optical Coherence Tomography　- Lessons From the French "Lotus Root" Registry.

BACKGROUND: Spontaneous reanalyzed coronary thrombus (SRCT) has been reported in autopsy series, but little is known about SRCT, and it is potentially under-diagnosed in clinical practice.Methods and Results:SRCT identified on OCT were included in a French multicenter series, the Lotus Root French Registry. A total of 34 SRCT were identified on OCT in 33 patients (23 male; median age, 56 years; IQR, 52-65 years); 23/33 patients (70%) presented with angina pectoris and/or dyspnea. Three angiographic aspects were distinguished retrospectively: braided, pseudo-dissected, and hazy. Stenosis severity on quantitative coronary analysis varied between 11% and 100% (median, 45%), whereas the reduction in lumen area on OCT varied between 20% and 92% (median, 68%). A typical "lotus root" aspect was confirmed on OCT, consisting of multiple circular concave-edged channels of varying size, numbering between 3 and 12 depending on the slice, separated by smooth-edged septa of high luminosity without posterior attenuation. OCT also served to guide treatment, with stenting in 91% of cases. During the 17-month follow-up 91% of patients had excellent evolution. One death and 3 ACS events occurred. CONCLUSIONS: In this large SRCT cohort, angiography had limited diagnostic value whereas OCT could be used to define disease characteristics and guide treatment of lesions inducing angina pectoris and/or silent myocardial ischemia. OCT-guided management was associated with good prognosis.

Delayed Formation of a Massive Atrial Hematoma After Coronary Intervention Manifesting With an Isolated Cough: Multimodality Imaging and Outcome.

Coronary artery perforation is a relatively rare but potentially life-threatening complication of percutaneous coronary intervention because it could result in cardiac tamponade; exceptionally, distal coronary perforation could cause an acute formation of a mural hematoma, which could also prove lethal without adequate management. We report an exceptional case of a 76-year-old man in whom an important left atrial hematoma formed progressively over weeks after a planned percutaneous coronary intervention and manifested with an isolated cough. Diagnosis was made using multimodality imaging. A conservative strategy was adopted and produced a favourable outcome.

Impact of Routine Fractional Flow Reserve on Management Decision and 1-Year Clinical Outcome of Patients With Acute Coronary Syndromes: PRIME-FFR (Insights From the POST-IT [Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease] and R3F [French FFR Registry] Integrated Multicenter Registries - Implementation of FFR [Fractional Flow Reserve] in Routine Practice).

BACKGROUND: Fractional flow reserve (FFR) is not firmly established as a guide to treatment in patients with acute coronary syndromes (ACS). Primary goals were to evaluate the impact of integrating FFR on management decisions and on clinical outcome of patients with ACS undergoing coronary angiography, as compared with patients with stable coronary artery disease. METHODS AND RESULTS: R3F (French FFR Registry) and POST-IT (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease), sharing a common design, were pooled as PRIME-FFR (Insights From the POST-IT and R3F Integrated Multicenter Registries - Implementation of FFR in Routine Practice). Investigators prospectively defined management strategy based on angiography before performing FFR. Final decision after FFR and 1-year clinical outcome were recorded. From 1983 patients, in whom FFR was prospectively used to guide treatment, 533 sustained ACS (excluding acute ST-segment-elevation myocardial infarction). In ACS, FFR was performed in 1.4 lesions per patient, mostly in left anterior descending (58%), with a mean percent stenosis of 58±12% and a mean FFR of 0.82±0.09. In patients with ACS, reclassification by FFR was high and similar to those with non-ACS (38% versus 39%; P=NS). The pattern of reclassification was different, however, with less patients with ACS reclassified from revascularization to medical treatment compared with those with non-ACS (P=0.01). In ACS, 1-year outcome of patients reclassified based on FFR (FFR against angiography) was as good as that of nonreclassified patients (FFR concordant with angiography), with no difference in major cardiovascular event (8.0% versus 11.6%; P=0.20) or symptoms (92.3% versus 94.8% angina free; P=0.25). Moreover, FFR-based deferral to medical treatment was as safe in patients with ACS as in patients with non-ACS (major cardiovascular event, 8.0% versus 8.5%; P=0.83; revascularization, 3.8% versus 5.9%; P=0.24; and freedom from angina, 93.6% versus 90.2%; P=0.35). These findings were confirmed in ACS explored at the culprit lesion. In patients (6%) in whom the information derived from FFR was disregarded, a dire outcome was observed. CONCLUSIONS: Routine integration of FFR into the decision-making process of ACS patients with obstructive coronary artery disease is associated with a high reclassification rate of treatment (38%). A management strategy guided by FFR, divergent from that suggested by angiography, including revascularization deferral, is safe in ACS.

Mechanisms of stent thrombosis analysed by optical coherence tomography: insights from the national PESTO French registry.

AIMS: Angiography has limited value for identifying the causes of stent thrombosis (ST). We studied a large cohort of patients by optical coherence tomography (OCT) to explore ST characteristics and mechanisms. METHODS AND RESULTS: A prospective multicentre registry was screened for patients with confirmed ST. Optical coherence tomography was performed after initial intervention to the culprit lesion (in 69% of cases in a deferred procedure). Stent thrombosis was classified as acute (AST), sub-acute (SAST), late (LST), and very late (VLST). Optical coherence tomography records were analysed in a central core lab. The analysis included 120 subjects aged 61.7 [51.4-70.7]; 89% male. Very late ST was the clinical presentation in 75%, LST in 6%, SAST in 15%, and AST in 4% of patients. Bare metal stents (BMS) were used in 39%, drug-eluting stents (DES) in 59% and bioresorbable vascular scaffolds in 2% of the cases. Optical coherence tomography identified an underlying morphological abnormality in 97% of cases, including struts malapposition (34%), neoatherosclerotic lesions (22%), major stent underexpansion (11%), coronary evagination (8%), isolated uncovered struts (8%), edge-related disease progression (8%), and neointimal hyperplasia (4%). Ruptured neoatherosclerotic lesions were more frequent with BMS than with DES (36 vs. 14%, P = 0.005), whereas coronary evaginations were more frequent with DES than with BMS (12 vs. 2%, P = 0.04). LST + VLST were mainly related to malapposition (31%) and neoatherosclerosis (28%), while prominent mechanisms for AST + SAST were malapposition (48%) and underexpansion (26%). CONCLUSION: In patients with confirmed ST, OCT imaging identified an underlying morphological abnormality in 97% of cases.

Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry.

BACKGROUND: There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. METHODS AND RESULTS: The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. CONCLUSION: This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Ticagrelor versus prasugrel in diabetic patients with an acute coronary syndrome. A pharmacodynamic randomised study.

Optimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention.

BACKGROUND: The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). OBJECTIVE: We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI. METHODS: We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥50%. RESULTS: One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17±14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6-22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index <16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p=0.9). CONCLUSION: In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index <16%.

ST elevation myocardial infarction with no structural lesions after a wasp sting.

BACKGROUND: Acute coronary syndromes after hymenoptera stings and other environmental exposures are referred to as the Kounis syndrome or allergic myocardial ischemia and infarction. CASE REPORT: We report the case of a 58-year-old man with transient inferior ST-segment elevation consistent with myocardial ischemia after a single wasp sting. Urgent cardiac catheterization revealed normal coronary arteries with a normal left ventriculogram. The evaluation and treatment of cardiac ischemia associated with an allergic reaction is discussed. CONCLUSION: ST elevation myocardial infarction after wasp envenomation is an exceptional and interesting pathology with a partially elucidated pathogenesis. The management of cardiac ischemia in this setting is uncertain.

High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.

OBJECTIVES: The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events. BACKGROUND: Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR. METHODS: A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month. RESULTS: Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70). CONCLUSIONS: Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.

Coronary artery spasm and dobutamine stress echocardiography.

AIMS: The aim of this article was to assess whether abnormal dobutamine stress echocardiography (DSE) can be due to a dobutamine-induced coronary spasm in patients with angiographically documented vasospastic coronary arteries. METHODS AND RESULTS: Between January 2004 and April 2008, we prospectively evaluated all patients with known or suspected coronary artery disease (CAD) referred to the echocardiography laboratory for dobutamine stress tests (6061 examinations). Those with abnormal DSE underwent coronary angiogram with a systematic methylergometrine intracoronary injection in the case of absence of significant coronary stenosis or spontaneous occlusive coronary spasm. Patients who had spontaneous occlusive coronary spasm or positive methylergometrine test, but no significant stenoses, were ultimately included in this study. About 581 patients had abnormal DSE, among them only 20 (3.4%) fulfilled the inclusion criteria. There were 15 males and 5 females, and mean age was 64.35 years (range 52-85); 8 patients had a known history of CAD and all of them had at least two established cardiovascular risk factors. The culprit vessel was the left anterior descending artery in 10 cases (50%), right coronary artery in 8 cases (40%), and left circumflex in 2 cases (10%). There was a systematic correspondence between the culprit arteries and dobutamine-induced wall motion abnormality territories. No complications occurred during examination or during the provocation test. All the patients were discharged with a calcium channel blocker and were doing well after 13 months of mean follow-up. CONCLUSION: Coronary artery spasm can be induced at DSE, but is a rare finding; it could, though, be clinically relevant as it may partly explain some erroneously labelled 'false-positive' examinations. Methylergometrine provocation test is a safe and advisable approach in such situations.

Intra-atrial thrombosis and pulmonary embolism complicating pacemaker leads for cardiac resynchronization therapy.

This is the first report of intracardiac thrombi and pulmonary embolism complicating pacemaker leads implanted for cardiac resynchronization therapy. Prompt diagnosis and successful therapy with a thrombolytic agent lead to a favourable outcome. This report suggests that long-term oral anticoagulation should be considered in patients with depressed left ventricular function undergoing cardiac resynchronization therapy in order to prevent this potentially serious complication.