Incidence, Clinical Characteristics, and Impact of Absent Echocardiographic Signs in Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: Echocardiography is the primary imaging modality for diagnosis of infective endocarditis (IE) in prosthetic valve endocarditis (PVE) including IE after transcatheter aortic valve implantation (TAVI). This study aimed to evaluate the characteristics and clinical outcomes of patients with absent compared with evident echocardiographic signs of TAVI-IE. METHODS: Patients with definite TAVI-IE derived from the Infectious Endocarditis after TAVI International Registry were investigated comparing those with absent and evident echocardiographic signs of IE defined as vegetation, abscess, pseudo-aneurysm, intracardiac fistula, or valvular perforation or aneurysm. RESULTS: Among 578 patients, 87 (15.1%) and 491 (84.9%) had absent (IE-neg) and evident (IE-pos) echocardiographic signs of IE, respectively. IE-neg were more often treated via a transfemoral access with a self-expanding device and had higher rates of peri-interventional complications (eg, stroke, major vascular complications) during the TAVI procedure (P < .05 for all). IE-neg had higher rates of IE caused by Staphylococcus aureus (33.7% vs 23.2%; P = .038) and enterococci (37.2% vs 23.8%; P = .009) but lower rates of coagulase-negative staphylococci (4.7% vs 20.0%, P = .001). IE-neg was associated with the same dismal prognosis for in-hospital mortality in a multivariate binary regression analysis (odds ratio: 1.51; 95% confidence interval [CI]: .55-4.12) as well as a for 1-year mortality in Cox regression analysis (hazard ratio: 1.10; 95% CI: .67-1.80). CONCLUSIONS: Even with negative echocardiographic imaging, patients who have undergone TAVI and presenting with positive blood cultures and symptoms of infection are a high-risk patient group having a reasonable suspicion of IE and the need for an early treatment initiation.

Perivalvular Extension of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. METHODS: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. RESULTS: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all). CONCLUSIONS: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes.

Use and outcomes of dual antiplatelet therapy for acute coronary syndrome in patients with chronic kidney disease: insights from the Canadian Observational Antiplatelet Study (COAPT).

Chronic kidney disease (CKD) increases the risk of adverse outcomes in acute coronary syndrome (ACS). The optimal regimen of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) in CKD poses a challenge due to the increased bleeding and clotting tendencies, particularly since patients with CKD were underrepresented in randomized controlled trials. We examined the practice patterns of DAPT prescription stratified by the presence of CKD. The multicentre prospective Canadian Observational Antiplatelet Study (COAPT) enrolled patients with ACS between December 2011 and May 2013. The present study is a subgroup analysis comparing type and duration of DAPT and associated outcomes among patients with and without CKD (eGFR < 60 ml/min/1.73 m2, calculated by CKD-EPI). Patients with CKD (275/1921, 14.3%) were prescribed prasugrel/ticagrelor less (18.5% vs 25.8%, p = 0.01) and had a shorter duration of DAPT therapy versus patients without CKD (median 382 vs 402 days, p = 0.003). CKD was associated with major adverse cardiovascular events (MACE) at 12 months (p < 0.001) but not bleeding when compared to patients without CKD. CKD was associated with MACE in both patients on prasugrel/ticagrelor (p = 0.017) and those on clopidogrel (p < 0.001) (p for heterogeneity = 0.70). CKD was associated with increased bleeding only among patients receiving prasugrel/ticagrelor (p = 0.007), but not among those receiving clopidogrel (p = 0.64) (p for heterogeneity = 0.036). Patients with CKD had a shorter DAPT duration and were less frequently prescribed potent P2Y12 inhibitors than patients without CKD. Overall, compared with patients without CKD, patients with CKD had higher rates of MACE and similar bleeding rates. However, among those prescribed more potent P2Y12 inhibitors, CKD was associated with more bleeding than those without CKD. Further studies are needed to better define the benefit/risk evaluation, and establish a more tailored and evidence-based DAPT regimen for this high-risk patient group.

Myocardial infarction with nonobstructive coronary artery disease (MINOCA): a review of pathophysiology and management.

PURPOSE OF REVIEW: Myocardial infarction with nonobstructive coronary artery disease (MINOCA) (≥ 50% stenosis) accounts for 5-8% of acute coronary syndrome (ACS) presentations. The demographic characteristics, risk factors, and management of patients with MINOCA differ from those with atherosclerotic ACS. The objective of this review is to provide a contemporary understanding of the epidemiology, pathophysiology, clinical presentation, and management of MINOCA. RECENT FINDINGS: MINOCA is increasingly being recognized as an important and distinct cause of myocardial infarction among patients presenting with ACS. The predominant pathophysiologic mechanisms of MINOCA include both coronary (epicardial vasospasm, coronary microvascular disorder, spontaneous coronary artery dissection, coronary thrombus/embolism) and noncoronary (Takotsubo cardiomyopathy, myocarditis) pathologies. Coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offers important investigative modalities to facilitate diagnosis for appropriate management of MINOCA patients. SUMMARY: MINOCA is an important cause of ACS observed in certain patients with unique challenges for diagnosis and management. A high index of suspicion and a comprehensive diagnostic evaluation are critical for early recognition and successful management.

Antithrombotic therapy after transcatheter aortic valve replacement: current perspective.

PURPOSE OF REVIEW: Transcatheter aortic valve replacement (TAVR) has expanded as a treatment option for severe aortic stenosis throughout the surgical risk spectrum. Decreasing procedural risk and inclusion of lower risk population has shifted the focus to optimization of postprocedural management and balancing the thrombotic and bleeding complications. In this review, we outline various patient and procedure related factors affecting choice of antithrombotic therapy post TAVR and provide an update of recent development in this area. RECENT FINDINGS: Multiple studies have confirmed the high incidence of both ischemic and bleeding complications in the early to midterm post-TAVR. In addition, new data has emerged for the role of high resolution computed tomography to detect decreased leaflet mobility and leaflet micro thrombi associated with implications for bioprosthetic valve dysfunction and cerebrovascular events post TAVR. Randomized clinical trials have reported increased bleeding with dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC) plus antiplatelet therapy. These findings suggest that aspirin monotherapy or OAC monotherapy likely provides the appropriate balance for antithrombotic protection and risk of bleeding. SUMMARY: Majority of patients undergoing TAVR have multiple comorbidities and are at increased risk of ischemic and bleeding complications. In the absence of robust clinical evidence, there is significant variability among guideline recommendations and antithrombotic therapy post TAVR across institutions. The available evidence confirms a high rate of bleeding with more potent and prolonged antithrombotic regimens without a documented benefit for clinical endpoints. The authors favor a conservative anti thrombotic approach and suggest monotherapy with aspirin or systemic anticoagulation based upon an individual's risk of thromboembolic complications. DAPT is reserved for patients with recent stenting and OAC plus aspirin is prescribed for patients with established CAD in the post TAVR setting.

Revascularization strategies for left main coronary artery disease: current perspectives.

PURPOSE OF REVIEW: Left main coronary artery disease (LMCAD) represents a high-risk subset of coronary artery disease with significant morbidity and mortality if not treated in a timely manner. In this review, we survey the contemporary evidence on the management of LMCAD, highlight advances, and provide in-depth review of data comparing surgical and percutaneous approaches. RECENT FINDINGS: LMCAD represents a heterogeneous condition and management should be guided by key clinical and anatomic factors. In recent years, there has been a wealth of published prospective data including results of the EXCEL and NOBLE trials. Coronary artery bypass graft (CABG), remains the gold standard for optimal long-term outcomes and the greatest benefit seen in patients with higher anatomic complexity and longer life expectancy. Percutaneous coronary intervention (PCI) offers a less-invasive approach with rapid recovery. PCI is optimal in situations when surgery cannot be offered in a timely manner due to hemodynamic instability, for high-risk surgical patients, or those with limited life expectancy, if LMCAD is anatomically simple. As a result of continued technological and procedural improvements in both PCI and CABG, cardiovascular specialists possess a growing armamentarium of approaches to treat LMCAD. Thus, center specialization and use of a heart team approach are increasingly vital, though barriers remain. SUMMARY: Emerging evidence continues to support CABG as the gold standard for achieving optimal long-term outcomes in patients with LMCAD. PCI offers a more expeditious approach with rapid recovery and is a safe and effective alternative in appropriately selected candidates.

Assessment and management of coronary artery disease in patients undergoing transcatheter aortic valve replacement.

PURPOSE OF REVIEW: Coronary artery disease (CAD) is commonly observed in patients undergoing transcatheter aortic valve replacement (TAVR). Significant variability exists across institutions for strategies used for CAD diagnosis and its management. The heart team often relies upon traditional practice patterns and the decision for revascularization by percutaneous coronary intervention (PCI) is influenced by patient, angiographic, operator, and system-related factors. RECENT FINDINGS: Contemporary coronary tomography angiography (CTA) shows significant promise for detection of clinically important CAD and preliminary data support CTA use for TAVR patients. The prognostic implications of CAD in a TAVR population remain unclear with studies showing conflicting data for the benefits of PCI. Recent trials show that medical management is an effective initial treatment strategy for stable CAD, a finding likely also applicable for asymptomatic and stable TAVR patients. In addition, PCI performed pre-TAVR, concomitant with TAVR or after TAVR has been shown to produce similar outcomes. Dual antiplatelet therapy (DAPT) is mandated after PCI but associated with increased risk of bleeding in TAVR population with accumulating evidence for single antiplatelet therapy (SAPT) post-TAVR unless DAPT or anticoagulation is indicated for another reason. SUMMARY: Although coronary angiography remains the predominant modality for CAD assessment, CTA is increasingly being used in TAVR patients. There is limited evidence to guide CAD management in TAVR patients with significant variability in practice patterns. Medical therapy is recommended for asymptomatic and stable CAD patients with applicability for TAVR population. Despite prior concerns, recent studies suggest successful coronary access post-TAVR and similar outcomes for PCI offered pre-TAVR, concomitant with TAVR and post-TAVR settings. Safety of DAPT should be an important consideration for PCI in TAVR patients. Ongoing studies will determine the preferred testing for CAD diagnosis, benefit of revascularization, timing of PCI, and optimum antithrombotic therapy for TAVR populations.

Percutaneous management of coronary bifurcation lesions: current perspective.

PURPOSE OF REVIEW: Coronary artery disease affecting bifurcations poses a challenge for percutaneous intervention. Several techniques and strategies for percutaneous management of bifurcation lesions have been described in the literature with variable data available for outcomes. In this review, we provide an overview of the strategies and techniques used for percutaneous intervention of bifurcation lesions with an update of recent technical developments and clinical evidence. RECENT FINDINGS: The coronary bifurcation lesions of both left main and other coronary segments are best treated with a provisional stenting strategy where main branch is treated with a stent placement and side branch intervention reserved for angiographically or physiologically determined hemodynamically significant residual stenosis despite application of a proximal stent optimization technique. When a provisional stent strategy is not likely to be successful due to anatomic or morphologic lesion characteristics and a large side branch or distal left main bifurcation is involved, an upfront bifurcation stenting strategy with double kissing crush technique may provide the optimum results. Coronary imaging and fractional flow determination may guide lesion specific management, facilitate device selection and improve clinical outcomes for percutaneous therapy for bifurcation lesions. SUMMARY: Despite advances in technology and procedural techniques, percutaneous intervention of coronary bifurcation lesions remains challenging and associated with higher adverse outcomes compared to non bifurcation lesions. Among the several bifurcation strategies, a provisional stenting approach is preferred for technical simplicity and better long term outcomes. Double kissing crush technique provides superior clinical results and should be preferred when a two stent strategy is indicated. Use of coronary imaging and physiology assessment should be incorporated in the algorithm of bifurcation interventions for greater technical and clinical success.

Distal transradial access for cardiac catheterization: A systematic scoping review.

OBJECTIVE: Systematically review the literature for cardiac catheterization and coronary angiography via distal transradial access (dTRA) and its outcomes. BACKGROUND: dTRA, via anatomical snuffbox, may have several advantages over conventional transradial access (cTRA) for percutaneous cardiac procedures, including easier left-sided access for aorto-coronary grafts, future proximal radial artery preservation, and patient and operator comfort. However, its procedural characteristics and safety profile remain unclear. METHODS: Ovid MEDLINE and EMBASE were searched from inception to September 2018. Two authors independently performed two-stage selection and data extraction. Reports assessing the dTRA approach for cardiac intervention in adults reporting any outcomes were eligible. Descriptive summary statistics were calculated from pooled data. RESULTS: A total of 19 publications comprising 4,212 participants undergoing dTRA were included. Mean age was 63.8 years, and 23.0% were female. dTRA was primarily undertaken for assessment of stable coronary artery disease (87.6%), with 41.7% for diagnostic procedures and 46.9% undergoing percutaneous coronary intervention. The overall success rate for undertaking the dTRA approach was 95.4% (69-100%). Complications occurred in 2.4% of cases, of which the leading complications were bleeding/hematoma (18.2%). Complication rates did not significantly differ between dTRA and cTRA. The occurrence of radial artery occlusion in patients undergoing dTRA was low (1.7%). CONCLUSIONS: Observational data demonstrate that dTRA is a safe and feasible method for percutaneous cardiac procedures, with high rates of procedural success and low rates of complication. As data comparing dTRA with cTRA remain limited, future high-quality randomized comparative studies are required.

Upstream anticoagulation for patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: Insights from the TOTAL trial.

OBJECTIVES: To assess the relationship between preprocedural anticoagulation use and clinical and angiographic outcomes. BACKGROUND: For patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the optimal timing of anticoagulant administration remains uncertain. METHODS: Patients enrolled in the TOTAL trial were stratified based on whether or not they had received any parenteral anticoagulant prior to randomization and PCI. Baseline and procedural characteristics were compared. For one-year clinical outcomes, Cox proportional modeling adjusted on a propensity score was used to analyze differences between groups. Angiographic endpoints were analyzed by logistic regression models adjusted for propensity scores. RESULTS: In the trial, 10,064 patients were enrolled and underwent PCI. Preprocedural anticoagulation was used in 6,381 patients (63%).The most common anticoagulant was intravenous unfractionated heparin (5,188, 81%). Patients who received preprocedural anticoagulation had higher rates of TIMI-2-3 or TIMI-3 flow and lower grades of thrombus prior to PCI. Pretreatment with anticoagulation was associated with lower use of bailout thrombectomy, GP IIb/IIIa inhibitors, and intra-aortic balloon pump. After adjustment, preprocedural anticoagulation was associated with lower rates of CABG and minor bleeding at 1 year but there were no significant differences in death, stroke, recurrent MI, cardiogenic shock, or congestive heart failure. CONCLUSIONS: Preprocedural anticoagulation is associated with improved flow and reduced thrombus in the IRA prior to PCI, less bailout thrombectomy during PCI but no difference in death, recurrent infarction, or heart failure at 1 year.

Randomized trial of primary PCI with or without routine manual thrombectomy.

BACKGROUND: During primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results. METHODS: We randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days. RESULTS: The primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02). CONCLUSIONS: In patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).

Long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in fibrinolytic-treated STEMI patients undergoing early PCI.

The long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in patients undergoing early percutaneous coronary intervention (PCI) after fibrinolytic therapy is unknown. From May 2014 to August 2016, 212 patients undergoing PCI within 24 h of Tenecteplase (TNK), Aspirin, and Clopidogrel for ST-elevated myocardial infarction (STEMI) were randomized at four Canadian sites to receive additional Clopidogrel or Ticagrelor initiated prior to PCI. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline), at 4 and 24 h post PCI, and follow-up appointment. A mixed-model analysis with time as the repeated measure and drug as the between-subjects factor was calculated using 2 separate 1 × 4 ANOVAs, with students t-tests used to compare drugs within each time point. Complete clinical follow-up data (median 115.0 days; IQR 80.3-168.8) was available in 50 patients (23.6%) randomized to either Clopidogrel (n = 23) or Ticagrelor (n = 27). Analyses revealed significant decreases in PRU from baseline to 4 h (261.4 vs. 71.7; Mdiff = - 189.7; p < 0.001) to 24 h (71.7 vs. 27.7; Mdiff = - 44.0; p < 0.001) to end of follow-up (27.7 vs.17.9; Mdiff = - 9.9. p = 0.016) for those randomized to Ticagrelor and significant decreases in PRU only from baseline to 4 h (271.3 vs. 200.8; Mdiff = - 70.5, p = < 0.001) in patients receiving Clopidogrel, and a significantly greater proportion of patients with adequate platelet inhibition (PRU < 208) on long-term follow-up (Clopidogrel, 82.6% vs. Ticagrelor, 100.0%; p = 0.038). Our results demonstrate that in patients undergoing PCI within 24 h of fibrinolysis for STEMI, Ticagrelor provides prolonged platelet inhibition compared with Clopidogrel.

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial.

BACKGROUND: Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. METHODS: The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. FINDINGS: Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015). INTERPRETATION: Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. FUNDING: Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.

Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI.

OBJECTIVES: Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI. METHODS AND RESULTS: Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, P<.001) and at 24 hours (34.5±35.0 and 153.5±75.5, respectively, P<.001). The primary end point was observed in 87.8% (n=65) in the ticagrelor-treated patients compared to 57.6% (n=38) of clopidogrel-treated patients, P<.001. CONCLUSION: Fibrinolysis-treated STEMI patients who received clopidogrel and aspirin at the time of fibrinolysis and were undergoing early PCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, https://clinicaltrials.gov/ct2/show/NCT01930591).

Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis.

BACKGROUND: The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. METHODS: We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. RESULTS: Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays. CONCLUSIONS: There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

Non-infarct related artery revascularization in ST-segment elevation myocardial infarction patients with multivessel disease.

PURPOSE OF REVIEW: Multivessel disease (MVD) is common in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) and is associated with significant risk of future cardiovascular (CV) events including short and longer-term mortality. In this review, we examine the pathophysiologic construct contributing to adverse prognosis of MVD in STEMI, relevant available evidence that currently guides the management of the noninfarct-related artery (IRA) stenosis and define the remaining knowledge gaps for future studies. RECENT FINDINGS: Results of recent small sized randomized trials, when pooled, suggest improvement in CV outcomes including CV mortality and repeat revascularization with revascularization of the non-IRA stenosis compared with medical management alone. In addition, there does not appear to be an increase in bleeding, contrast-induced nephropathy or stroke, as suggested by earlier observational data. SUMMARY: These recent data have led to a Class IIb recommendation in the American College of Cardiology/American Heart Association guidelines stating that non-IRA revascularization may be considered in selected patients with STEMI and MVD who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure. The ongoing COMPLETE and CULPRIT-SHOCK studies will provide additional data to further inform the role of non-IRA revascularization and its timing in the management of these patients.

Subclinical bioprosthetic aortic valve thrombosis: clinical and translational implications.

PURPOSE OF REVIEW: A recently published study has alerted the cardiovascular community to the existence of a significant and previously unrecognized risk of subclinical valve thrombosis following implantation of surgical and catheter-based bioprosthetic valves. The purpose of this article is to review our current understanding of this new clinical entity and to identify unanswered questions and areas for future research. RECENT FINDINGS: Subclinical bioprosthetic valve thrombosis (BPVT) is a more common phenomenon than previously appreciated. It appears that the incidence of BPVT is higher following transcatheter aortic valve replacement compared with surgical aortic valve replacement. Four-dimensional computed tomography (CT) is the most sensitive imaging modality for detection of leaflet immobility and subclinical BPVT. Certain echocardiographic findings, such as increasing transaortic gradients, increased cusp thickness and abnormal cusp mobility, predict the presence of BPVT on four-dimensional CT. There is a growing body of evidence linking subclinical BPVT with premature valvular hemodynamic deterioration and structural valve degeneration. Furthermore, subclinical leaflet thrombosis may constitute a nidus for unrecognized subacute cerebral or other thromboembolic events. Oral anticoagulation seems effective in both the prevention and treatment of BPVT. SUMMARY: Subclinical valve thrombosis is an important and underappreciated cause of early bioprosthetic valve failure. Although several recent studies have improved our understanding of this newly recognized clinical entity, a number of questions remain unanswered. Further studies are warranted to elucidate the true incidence of subclinical BPVT, its clinical consequences, as well as the optimal antithrombotic regimen following bioprosthetic valve implantation. The subgroups of patients at highest risk of BPVT will need to be identified for risk stratification purposes. Several ongoing clinical trials will shed some light on these important issues.

Clinical outcomes after trans-catheter aortic valve replacement in men and women in Ontario, Canada.

OBJECTIVE: Our objective was to evaluate sex-differences in outcomes after trans-catheter aortic valve replacement (TAVR) in a population-based cohort from Ontario, Canada. BACKGROUND: Prior studies comparing outcomes in men and women after TAVR have yielded divergent results. Some studies have suggested that women have better survival than men while others have not corroborated this finding. METHODS: A retrospective observational cohort study was conducted using chart abstraction data on all TAVR procedures performed between 2007 and 2013 in Ontario, Canada. Patients who had emergency TAVR procedures were excluded. The primary outcome was all-cause mortality at 30-days and 1-year. Secondary outcomes included mortality at last follow-up, cause-specific, and all-cause hospital readmission. Inverse probability of treatment weighting (IPTW) using propensity score was used to adjust for baseline differences between men and women. RESULTS: The final study cohort consisted of 453 women and 546 men with a mean follow-up of 3.5 years. Women were generally older and more frail but had less comorbid conditions. Women had lower unadjusted mean EuroScores (7% ± 5% vs 8% ± 7%; P = 0.008), but underwent significantly more trans-apical procedures (26.5% vs 19.2%; P = 0.006) than men. After IPTW, the groups were well balanced. Although mortality was numerically higher for women at 30-days (7.2% vs 5.4%), this was not statistically significant (P = 0.34). At 1-year, there was no difference in mortality (18.2% vs 19.2%; P = 0.85). There were no significant differences in all-cause readmission. CONCLUSION: In this population-based cohort including all patients undergoing TAVR, mortality or all-cause readmission were not significantly different between men and women. © 2017 Wiley Periodicals, Inc.

Factors associated with length of stay following trans-catheter aortic valve replacement - a multicenter study.

BACKGROUND: Most patients undergoing Transcatheter aortic valve implantation (TAVR) are elderly with significant co-morbidities and there is limited information available regarding factors that influence length of stay (LOS) post-procedure. The aim of this study was to identify the patient, and procedural factors that affect post-TAVR LOS using a contemporary multinational registry. METHODS: We conducted a retrospective cohort study, with patients recruited from three high volume tertiary institutions. The primary outcome was the LOS post-TAVR procedure. We examined patient and procedural factors in a cause-specific Cox multivariable regression model to elucidate their effect on LOS, accounting for the competing risk of post-procedural death. Hazard ratios (HR) greater than 1 indicate a shorter LOS, while HRs less than 1 indicate a longer LOS. RESULTS: The cohort consisted of 809 patients. Patient factors associated with longer LOS were older age, prior atrial fibrillation, and greater patient urgency. Patient factors associated with shorter LOS were lower NYHA class, higher ejection fraction and higher mean aortic valve gradients. Procedural characteristics associated with shorter LOS were conscious sedation (HR = 1.19, 95% CI 1.06-1.35, p = 0.004). Transapical access was associated with prolonged LOS (HR = 0.49, 95% CI 0.41-0.58, p < 0.001). CONCLUSION: This multicenter study identified potentially modifiable patient and procedural factors associated with a prolonged LOS. Future research is needed to determine if interventions focused on these factors will translate to a shorter LOS.

Arrhythmia burden in elderly patients with severe aortic stenosis as determined by continuous electrocardiographic recording: toward a better understanding of arrhythmic events after transcatheter aortic valve replacement.

BACKGROUND: This study sought to evaluate the prevalence of previously undiagnosed arrhythmias in candidates for transcatheter aortic valve replacement (TAVR) and to determine the impact on therapy changes and arrhythmic events after the procedure. METHODS AND RESULTS: A total of 435 candidates for TAVR underwent 24-hour continuous ECG monitoring the day before the procedure. Newly diagnosed arrhythmias were observed in 70 patients (16.1%) before TAVR: paroxysmal atrial fibrillation (AF)/atrial tachycardia (AT) in 28, advanced atrioventricular block or severe bradycardia in 24, nonsustained ventricular tachycardia in 26, and intermittent left bundle-branch block in 3 patients. All arrhythmic events but one were asymptomatic and led to a therapy change in 43% of patients. In patients without known AF/AT, the occurrence of AF/AT during 24-hour ECG recording was associated with a higher rate of 30-day cerebrovascular events (7.1% versus 0.4%; P=0.030). Among the 53 patients with new-onset AF/AT after TAVR, 30.2% had newly diagnosed paroxysmal AF/AT before the procedure. In patients who needed permanent pacemaker implantation after the procedure (n=35), 31.4% had newly diagnosed advanced atrioventricular block or severe bradycardia before TAVR. New-onset persistent left bundle-branch block after TAVR occurred in 37 patients, 8.1% of whom had intermittent left bundle-branch block before the procedure. CONCLUSIONS: Newly diagnosed arrhythmias were observed in approximately a fifth of TAVR candidates, led to a higher rate of cerebrovascular events, and accounted for a third of arrhythmic events after the procedure. This high arrhythmia burden highlights the importance of an early diagnosis of arrhythmic events in such patients to implement the appropriate therapeutic measures earlier.