Differential modulation of polyunsaturated fatty acids in patients with myocardial infarction treated with ticagrelor or clopidogrel.

Untargeted metabolomics is used to refine the development of biomarkers for the diagnosis of cardiovascular disease. Myocardial infarction (MI) has major individual and societal consequences for patients, who remain at high risk of secondary events, despite advances in pharmacological therapy. To monitor their differential response to treatment, we performed untargeted plasma metabolomics on 175 patients from the platelet inhibition and patient outcomes (PLATO) trial treated with ticagrelor and clopidogrel, two common P2Y12 inhibitors. We identified a signature that discriminates patients, which involves polyunsaturated fatty acids (PUFAs) and particularly the omega-3 fatty acids docosahexaenoate and eicosapentaenoate. The known cardiovascular benefits of PUFAs could contribute to the efficacy of ticagrelor. Our work, beyond pointing out the high relevance of untargeted metabolomics in evaluating response to treatment, establishes PUFA metabolism as a pathway of clinical interest in the recovery path from MI.

Rubidium-82 Positron Emission Tomography With Intravenous Ergonovine to Diagnose Vasospastic Angina.

The gold standard to diagnose vasospastic angina is intracoronary reactivity testing, which is performed selectively at dedicated centres. Noninvasive imaging with single-photon emission computerized tomography (SPECT) or echocardiography does not enable accurate localization of spasm or quantification of change in myocardial perfusion in response to an abnormal vasoreactivity. Rubidium-82 positron emission tomography myocardial perfusion imaging (82Rb PET-MPI) with intravenous ergonovine was used to diagnose refractory vasospastic angina in a patient with a complex ischemic syndrome, recent coronary stenting, and persistent atypical angina despite maximal tolerable doses of guideline-directed medical therapy.

Outcomes of left main revascularization in patients with acute coronary syndromes and stable ischemic heart disease: Analysis from the EXCEL trial.

BACKGROUND: Prompt revascularization is often required in acute coronary syndromes (ACS), whereas stable ischemic heart disease (SIHD) may allow for more measured procedural planning. Whether the acuity of presentation preferentially affects outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LMCAD) is unknown. We investigated whether the acuity of presentation discriminated patients who derived a differential benefit from PCI versus CABG in the randomized Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial. METHODS: We used multivariable Cox models to assess the interaction between the acuity of presentation, type of revascularization and outcomes in patients with low or intermediate SYNTAX scores enrolled in EXCEL. RESULTS: At baseline, 1151 patients (60.7%) presented with SIHD and 746 patients (39.3%) presented with an ACS. The acuity of presentation was not associated with the primary endpoint of all-cause death, MI, or stroke at 3 years (multivariable adjusted hazard ratio [HR] 0.94; 95% CI 0.70-1.26, P = .64). The primary endpoint rate was similar in patients assigned to PCI versus CABG whether they presented with SIHD (adjusted HR 1.04; 95% CI 0.73-1.48]) or with ACS (HR 0.82; 95% CI 0.54-1.26) (Pinteraction = .34). CONCLUSIONS: The acuity of presentation did not predict outcomes in patients with LMCAD undergoing revascularization, nor did it discriminate patients who derive greater event-free survival from PCI versus CABG.

Surgery Versus Transcatheter Interventions for Significant Paravalvular Prosthetic Leaks.

OBJECTIVES: This study sought to assess the relative merit of surgical correction (SC) versus transcatheter reduction on long-term outcomes in patients with significant paravalvular leak (PVL) refractory to medical therapy. BACKGROUND: PVL is the most frequent dysfunction following prosthetic valve replacement. Although repeat surgery is the gold standard, transcatheter reduction (TR) of PVL has been associated with reduced mortality. METHODS: From 1994 to 2014, 231 patients underwent SC (n = 151) or TR (n = 80) PVL correction. Propensity matching and Cox proportional hazards regression models were used to assess the effect of either intervention on long-term rates of all-cause death or hospitalization for heart failure. Survival after TR and SC were further compared with the survival in a matched general population and to matched patients undergoing their first surgical valve replacement. RESULTS: Over a median follow-up of 3.5 years, SC was associated with an important reduction in all-cause death or hospitalization for heart failure compared with TR (hazard ratio: 0.28; 95% confidence interval: 0.18 to 0.44; p < 0.001). There was a trend towards reduced all-cause death following SC versus TR (hazard ratio: 0.61; 95% confidence interval: 0.37 to 1.02; p = 0.06). Neither intervention normalized survival when compared with a general population or patients undergoing their first surgical valve replacement. CONCLUSIONS: In patients with significant prosthetic PVL, surgery is associated with better long-term outcomes compared with transcatheter intervention, but results in important perioperative mortality and morbidity. Future studies are needed in the face of increasing implementation of transcatheter PVL interventions across the world.

The wise radialist's guide to optimal transfemoral access: Selection, performance, and troubleshooting.

Transradial access (TRA) has reduced vascular access-site complication (VASC) and bleeding rates in patients undergoing coronary angiography and intervention. A "radial-first" approach should be adopted and indications of TRA extended in order to maximize its beneficial effect. However, in certain clinical scenarios, transfemoral access (TFA) is a preferable or a mandatory route to successfully perform the procedure. Since the widespread adoption of TRA, a paradoxical increase in VASC rates has been observed in patients undergoing TFA, which might be attributed to a combination of increased risk profile of both the procedures and the patients, and a loss of skills in securing TFA by those who are now default radial operators. In the present article we provide recommendations on how to optimize patient selection for TRA and TFA, how to manage access site crossover, and how to perform state-of-the-art femoral artery puncture. © 2016 Wiley Periodicals, Inc.

Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris.

Alongside the remarkable advances in medical and invasive therapies for the treatment of ischemic heart disease, an increasing number of patients with advanced coronary artery disease unsuitable for revascularization continue to suffer from angina pectoris despite optimal medical therapy. Patients with chronic angina have poor quality of life and increased levels of anxiety and depression. A considerable number of innovative therapeutic modalities for the treatment of chronic angina have been investigated over the years; however, none of these therapeutic options has become a standard of care, and none are widely utilized. Current treatment options for refractory angina focus on medical therapy and secondary risk factor modification. Interventions to create increased pressure in the coronary sinus may alleviate myocardial ischemia by forcing redistribution of coronary blood flow from the less ischemic subepicardium to the more ischemic subendocardium, thus relieving symptoms of ischemia. Percutaneous, transvenous implantation of a balloon expandable, hourglass-shaped, stainless steel mesh in the coronary sinus to create a fixed focal narrowing and to increase backwards pressure, may serve as a new device-based therapy destined for the treatment of refractory angina pectoris.

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access: The Campeau Radial Paradox.

OBJECTIVES: The purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed. BACKGROUND: The recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted. METHODS: Logistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort. RESULTS: A total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%. CONCLUSIONS: In a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators.

Importance of angina in patients with coronary disease, heart failure, and left ventricular systolic dysfunction: insights from STICH.

BACKGROUND: Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina. OBJECTIVES: This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD. METHODS: We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long-term clinical outcomes. RESULTS: At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01). CONCLUSIONS: Angina does not predict all-cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Transcatheter reduction of paravalvular leaks: a systematic review and meta-analysis.

BACKGROUND: Significant paravalvular leak (PVL) after surgical valve replacement can result in intractable congestive heart failure and hemolytic anemia. Because repeat surgery is performed in only few patients, transcatheter reduction of PVL is emerging as an alternative option, but its safety and efficacy remain uncertain. In this study we sought to assess whether a successful transcatheter PVL reduction is associated with an improvement in clinical outcomes. METHODS: We identified 12 clinical studies that compared successful and failed transcatheter PVL reductions in a total of 362 patients. A Bayesian hierarchical meta-analysis was performed using cardiac mortality as a primary end point. The combined occurrence of improvement in New York Heart Association functional class or hemolytic anemia and the need for repeat surgery, were used as secondary end points. RESULTS: A successful transcatheter PVL reduction was associated with a lower cardiac mortality rate (odds ratio [OR], 0.08; 95% credible interval [CrI], 0.01-0.90) and with a superior improvement in functional class or hemolytic anemia, compared with a failed intervention (OR, 9.95; 95% CrI, 2.10-66.73). Fewer repeat surgeries were also observed after successful procedures (OR, 0.08; 95% CrI, 0.01-0.40). CONCLUSIONS: A successful transcatheter PVL reduction is associated with reduced all-cause mortality and improved functional class in patients deemed unsuitable for surgical correction.

Efficacy of a device to narrow the coronary sinus in refractory angina.

BACKGROUND: Many patients with coronary artery disease who are not candidates for revascularization have refractory angina despite standard medical therapy. The balloon-expandable, stainless steel, hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium. METHODS: We randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina (on a scale from I to IV, with higher classes indicating greater limitations on physical activity owing to angina) and myocardial ischemia, who were not candidates for revascularization, to implantation of the device (treatment group) or to a sham procedure (control group). The primary end point was the proportion of patients with an improvement of at least two CCS angina classes at 6 months. RESULTS: A total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02). The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly improved in the treatment group, as compared with the control group (improvement on a 100-point scale, 17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography. At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient had died and 3 had had a myocardial infarction. CONCLUSIONS: In this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant improvement in symptoms and quality of life in patients with refractory angina who were not candidates for revascularization. (Funded by Neovasc; COSIRA ClinicalTrials.gov number, NCT01205893.).

A phase II, sham-controlled, double-blinded study testing the safety and efficacy of the coronary sinus reducer in patients with refractory angina: study protocol for a randomized controlled trial.

BACKGROUND: A growing population of patients lives with severe coronary artery disease not amenable to coronary revascularization and with refractory angina despite optimal medical therapy. Percutaneous reduction of the coronary sinus is an emerging treatment for myocardial ischemia that increases coronary sinus pressure to promote a transcollateral redistribution of coronary artery in-flow from nonischemic to ischemic subendocardial territories. A first-in-man study has demonstrated that the percutaneous reduction of the coronary sinus can be performed safely in such patients. The COSIRA trial seeks to assess whether a percutaneous reduction of the coronary sinus can improve the symptoms of refractory angina in patients with limited revascularization options. METHODS/DESIGN: The COSIRA trial is a phase II double-blind, sham-controlled, randomized parallel trial comparing the percutaneously implanted coronary sinus Reducer (Neovasc Inc, Richmond, BC, Canada) to a sham implantation in 124 patients enrolled in Canada, Belgium, England, Scotland, Sweden and Denmark. All patients need to have stable Canadian Cardiovascular Society (CCS) class III or IV angina despite optimal medical therapy, with evidence of reversible ischemia related to disease in the left coronary artery, and a left ventricular ejection fraction >25%. Participants experiencing an improvement in their angina ≥2 CCS classes six months after the randomization will meet the primary efficacy endpoint. The secondary objective of this trial is to test whether coronary sinus Reducer implantation will improve left ventricular ischemia, as measured by the improvement in dobutamine echocardiogram wall motion score index and in time to 1 mm ST-segment depression from baseline to six-month post-implantation. DISCUSSION: Based on previous observations, the COSIRA is expected to provide a significant positive result or an informative null result upon which rational development decisions can be based. Patient safety is a central concern and extensive monitoring should allow an appropriate investigation of the safety related to the coronary sinus Reducer. TRIAL REGISTRATION: ClinicalTrials.gov identifier - NCT01205893.

Immediate vs. delayed stenting in acute myocardial infarction: a systematic review and meta-analysis.

AIMS: To conduct a meta-analysis of studies comparing immediate versus delayed stenting in populations where primary percutaneous coronary intervention (PCI) or early invasive revascularisation was the initial mode of reperfusion. METHODS AND RESULTS: We identified five non-randomised studies and one randomised trial for a total of 590 patients in studies comparing immediate to delayed stenting in populations where primary PCI or early invasive revascularisation was the initial mode of reperfusion. In non-randomised studies, delayed stenting was associated with a reduction of procedure-related angiographic events (OR=0.13, 95% credible interval [CrI]: 0.03- 0.36). No differences were observed in the rates of major bleeding (OR=0.81, 95% CrI: 0.01-13.42) and major adverse cardiac events (OR=0.40, 95% CrI: 0.09-1.91), between delayed and immediate stenting. In one randomised trial, delayed stenting was associated with a reduction in myocardial infarction during hospitalisation (39% vs. 60%; relative risk [RR]=0.55, 95% confidence interval [CI]: 0.39-0.80). None of the patients assigned to delayed stenting experienced a major adverse cardiac event in the interval between the initial angiogram and the stenting. CONCLUSIONS: Delayed stent implantation is associated with better angiographic outcomes. Randomised trials are required to assess whether delayed stenting translates into better long-term cardiac outcomes.

Percutaneous coronary interventions and cardiovascular outcomes for patients with chronic total occlusions.

OBJECTIVES: This study sought to assess the benefits of a coronary chronic total occlusion CTO recanalization after adjusting for the case-mix and the propensity to undergo the CTO intervention in a population of patients with stable coronary artery disease. BACKGROUND: The benefits of percutaneous recanalization of CTO are disputed. METHODS: In 1,602 patients with a least one CTO and treated by percutaneous coronary intervention (PCI), we derived a propensity score to undergo a CTO recanalization by comparing the characteristics of patients who did (n = 346) and did not (n = 1,256) undergo a CTO PCI attempt. Among the patients who underwent a CTO PCI attempt, we identified the angiographic predictors of failure. The primary analysis was ultimately performed by looking at the association between the outcome of the CTO recanalization and the survival free of death and cardiovascular rehospitalizations. Sensitivity analyses were performed by adjusting for the propensity to undergo a CTO recanalization, for the anatomical predictors of failure, and for the extent of coronary artery revascularization achieved. RESULTS: A successful CTO recanalization was not significantly associated with survival free of death and cardiovascular rehospitalization (HR = 0.90, 95% CI 0.64-1.25). Even more conservative hazards ratio point estimates were obtained with the sensitivity analyses. CONCLUSIONS: Successful percutaneous CTO recanalization is not associated with survival free of death and cardiovascular hospitalizations in a contemporary population of patients with symptomatic coronary artery disease.