The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.

Tricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options. The tricuspid valve is complex anatomically, lying adjacent to important anatomic structures such as the right coronary artery and the atrioventricular node, and is the passageway for permanent pacemaker leads into the right ventricle. In addition, the mechanism of tricuspid pathology varies widely between patients, which can be due to primary, secondary, or a combination of causes, meaning that it is not possible for 1 type of device to be suitable for treatment of all cases of tricuspid valve disease. To best visualize the pathology, several modalities of advanced cardiac imaging are often required, including transthoracic echocardiography, transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, to best visualize the pathology. This detailed imaging provides important information for choosing the ideal transcatheter treatment options for patients with tricuspid valve disease, taking into account the need for the lifetime management of the patient. This review highlights the important background, anatomic considerations, therapeutic options, and future directions with regard to treatment of tricuspid valve disease.

Comparing Anticoagulation Strategies for Venous Thromboembolism Associated With Active Cancer: A Systematic Review and Meta-Analysis.

Background: Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE). Objectives: The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer. Methods: Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses. Results: Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88). Conclusions: DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis.

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

Considerations on the Management of Acute Postoperative Ischemia After Cardiac Surgery: A Scientific Statement From the American Heart Association.

Acute postoperative myocardial ischemia (PMI) after cardiac surgery is an infrequent event that can evolve rapidly and become a potentially life-threatening complication. Multiple factors are associated with acute PMI after cardiac surgery and may vary by the type of surgical procedure performed. Although the criteria defining nonprocedural myocardial ischemia are well established, there are no universally accepted criteria for the diagnosis of acute PMI. In addition, current evidence on the management of acute PMI after cardiac surgery is sparse and generally of low methodological quality. Once acute PMI is suspected, prompt diagnosis and treatment are imperative, and options range from conservative strategies to percutaneous coronary intervention and redo coronary artery bypass grafting. In this document, a multidisciplinary group including experts in cardiac surgery, cardiology, anesthesiology, and postoperative care summarizes the existing evidence on diagnosis and treatment of acute PMI and provides clinical guidance.

P2Y12 Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions.

BACKGROUND: It remains unclear whether P2Y12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). OBJECTIVES: We sought to assess the effects of P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity. METHODS: We pooled patient-level data from randomized controlled trials comparing P2Y12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding. RESULTS: Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; Pinteraction = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; Pinteraction = 0.920). CONCLUSIONS: P2Y12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853).

Sex-Related Outcomes of Medical, Percutaneous, and Surgical Interventions for Coronary Artery Disease: JACC Focus Seminar 3/7.

Biological and sociocultural differences between men and women are complex and likely account for most of the variations in the epidemiology and treatment outcomes of coronary artery disease (CAD) between the 2 sexes. Worse outcomes in women have been described following both conservative and invasive treatments of CAD. For example, increased levels of residual platelet reactivity during treatment with antiplatelet drugs, higher rates of adverse cardiovascular outcomes following percutaneous coronary revascularization, and higher operative and long-term mortality after coronary bypass surgery have been reported in women compared with in men. Despite the growing recognition of sex-specific determinants of outcomes, representation of women in clinical studies remains low and sex-specific management strategies are generally not provided in guidelines. This review summarizes the current evidence on sex-related differences in patients with CAD, focusing on the differential outcomes following medical therapy, percutaneous coronary interventions, and coronary artery bypass surgery.

Perioperative management of P2Y12 inhibitors in patients undergoing cardiac surgery within 1 year of PCI.

AIMS: To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding. CONCLUSION: Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: An ADAPT-DES Substudy.

OBJECTIVES: This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD). BACKGROUND: The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined. METHODS: The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with ≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of >0.5 mg/dL or a relative increase of ≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. The primary endpoint was the 2-year rate of net adverse clinical events (NACE): All-cause mortality, myocardial infarction (MI), definite or probable stent thrombosis, or major bleeding. RESULTS: Of 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted HR: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95% CI: 1.22-2.55; MI, HR: 1.67; 95% CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95% CI: 1.10-2.65; and major bleeding, HR: 1.38; 95% CI: 1.06-1.80). Compared with the CA-AKI-/CKD- group, the CA-AKI+/CKD- (HR: 1.83; 95% CI: 1.33-2.52), CA-AKI-/CKD+ (HR: 1.56; 95% CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95% CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95% CI: 1.65-4.31) groups were at higher risk of NACE. CONCLUSIONS: CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

Contemporary coronary artery bypass graft surgery and subsequent percutaneous revascularization.

Patients who have undergone coronary artery bypass graft (CABG) surgery are susceptible to bypass graft failure and progression of native coronary artery disease. Although the saphenous vein graft (SVG) was traditionally the most-used conduit, arterial grafts (including the left and right internal thoracic arteries and the radial artery) have improved patency rates. However, the need for secondary revascularization remains common, and percutaneous coronary intervention (PCI) has become the most common modality of secondary revascularization after CABG surgery. Procedural characteristics and clinical outcomes differ considerably from those associated with PCI in patients without previous CABG surgery, owing to altered coronary anatomy and differences in conduit pathophysiology. In particular, SVG PCI carries an increased risk of complications, and operators are shifting their focus towards embolic protection strategies and complex native-vessel interventions, increasingly using SVGs as conduits to facilitate native-vessel PCI rather than pursuing SVG PCI. In this Review, we discuss the differences in conduit pathophysiology, changes in CABG surgery techniques, and the latest evidence in terms of PCI in patients with previous CABG surgery, with a particular emphasis on safety and long-term efficacy. We explore the subject of contemporary CABG surgery and subsequent percutaneous revascularization in this complex patient population.

Perioperative risk and antiplatelet management in patients undergoing non-cardiac surgery within 1 year of PCI.

Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, especially in patients with recent percutaneous coronary intervention (PCI). We aimed to illustrate the types and timing of different surgeries occurring after PCI, and to evaluate the risk of thrombotic and bleeding events according to the perioperative antiplatelet management. Patients undergoing urgent or elective non-cardiac surgery within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, or stent thrombosis) at 30 days. Perioperative bleeding was defined as ≥ 2 units of blood transfusion. A total of 1092 surgeries corresponding to 747 patients were classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones, and were associated with an increased risk of both MACE and bleeding. Preoperative interruption of antiplatelet therapy (of any kind) occurred in 44.6% of all NCS and was more likely for procedures occurring later post-PCI and at intermediate risk. There was no significant association between interruption of antiplatelet therapy and adverse cardiac events. Among patients undergoing NCS within 1 year of PCI, perioperative ischemic and bleeding events primarily depend on the estimated surgical risk and urgency of the procedure, which are increased early after PCI. Preoperative antiplatelet interruption was not associated with an increased risk of cardiac events.

P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients' characteristics. DESIGN: Individual patient level meta-analysis of randomised controlled trials. DATA SOURCES: Searches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data. ELIGIBILITY CRITERIA: Randomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. MAIN OUTCOME MEASURES: The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. RESULTS: The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P<0.001; τ2=0.03), which was consistent across subgroups, except for type of P2Y12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y12 inhibitor rather than clopidogrel was part of the DAPT regimen. CONCLUSIONS: P2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. REGISTRATION: PROSPERO CRD42020176853.

Three dimensional reconstruction of coronary artery stents from optical coherence tomography: experimental validation and clinical feasibility.

The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps: 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and final stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro-computed tomography (µCT) and stereoscopy as references. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. The experimental and clinical studies showed that our algorithm (1) can reproduce the complex spatial stent configuration with high precision and reproducibility, (2) is feasible in 3D reconstructing stents deployed in bifurcations, and (3) enables CFD studies to assess the local hemodynamic environment within the stent. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can lay the ground for optimization of stenting procedures, patient-specific computational stenting simulations, and research and development of new stent scaffolds and stenting techniques.

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes.

OBJECTIVES: The aim of this study was to evaluate 1-year outcomes of valve-in-mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves. METHODS: A multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites. RESULTS: Between February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation. CONCLUSIONS: At 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement-induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC.

Anatomic classification of mitral annular calcification for surgical and transcatheter mitral valve replacement.

BACKGROUND AND AIM OF THE STUDY: A systematic approach to quantify mitral annular calcification (MAC) in all-comers by multidetector computed tomography (MDCT) is essential to guide treatment, but lacking. METHODS: From September 2015 to July 2019, 82 patients with MAC underwent MDCT at two institutions to evaluate for surgical mitral valve replacement (SMVR), transcatheter mitral valve replacement (TMVR), or medical management. Type 1 MAC was defined as <270° annular calcium and Type 2 as ≥270°. Absence/presence of predicted left ventricular outflow tract (LVOT) obstruction with virtual valve placement was used to further define Type 2 MAC into 2A/B for our treatment algorithm. RESULTS: Type 1 MAC was present in 51.2%, Type 2A in 18.3%, and Type 2B in 30.5%. Operable Type 1 patients (50.0%) underwent hybrid transatrial TMVR or SMVR. Type 2A underwent a variety of treatments, and Type 2B surgical candidates (40.0%) underwent hybrid transatrial TMVR secondary to difficult suture anchoring with significant MAC and predicted LVOT obstruction. At a follow-up of 29.6 ± 12.0 months, mortality was 42.7% with 46.3% in the intervention group and 39.0% in the medical group (p = 0.47). All percutaneous TMVR patients expired. This translated to a disproportionate number of Type 2A deaths (80.0% with intervention), but all were high/extreme surgical risk. The hybrid TMVR group consisted of 95.0% Type 1/2B patients and had a lower Society of Thoracic Surgeons predicted risk of operative mortality (7.4% vs. 9.2%, p = 0.43)/mortality. CONCLUSIONS: The highest mortality was seen in percutaneous TMVR Type 2A MAC patients, but they were at the greatest risk. Here we provide an objective MAC treatment algorithm for all-comers based on operability/anatomy.

Selection of the Optimal Candidate to MitraClip for Secondary Mitral Regurgitation: Beyond Mitral Valve Morphology.

Secondary mitral regurgitation (MR) occurs despite structurally normal valve apparatus due to an underlying disease of the myocardium leading to disruption of the balance between tethering and closing forces with ensuing failure of leaflet coaptation. In patients with heart failure (HF) and left ventricular dysfunction, secondary MR is independently associated with poor outcome, yet prognostic benefits related to the correction of MR have remained elusive. Surgery is not recommended for the correction of secondary MR outside coronary artery bypass grafting. Percutaneous mitral valve repair (PMVR) with MitraClip implantation has recently evolved as a new transcatheter treatment option of inoperable or high-risk patients with severe MR, with promising results supporting the extension of guideline recommendations. MitraClip is highly effective in reducing secondary MR in HF patients. However, the derived clinical benefit is still controversial as two randomized trials directly comparing PMVR vs. optimal medical therapy in severe secondary MR yielded virtually opposite conclusions. We reviewed current evidence to identify predictors of PMVR-related outcomes in secondary MR useful to improve the timing and the selection of patients who would derive maximal benefit from MitraClip intervention. Beyond mitral valve anatomy, optimal candidate selection should rely on a comprehensive diagnostic workup and a fine-tuned risk stratification process aimed at (i) recognizing the substantial heterogeneity of secondary MR and its complex interaction with the myocardium, (ii) foreseeing hemodynamic consequences of PMVR, (iii) anticipating futility and (iv) improving symptoms, quality of life and overall survival.

Prevalence and prognostic impact of hsCRP elevation are age-dependent in women but not in men undergoing percutaneous coronary intervention.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) predicts outcomes after percutaneous coronary intervention (PCI). OBJECTIVE: We studied the prevalence and prognostic impact of hsCRP elevation according to age in men and women undergoing PCI. METHODS: We included patients undergoing PCI at our center from 2010 until 2017, excluding those with myocardial infarction (MI) on presentation, neoplastic disease and hsCRP >10 mg/L at baseline. Elevated hsCRP was defined as >3 mg/L. The outcome of interest was major adverse cardiac events (MACE) consisting of all-cause death, MI and target vessel revascularization. The association between hsCRP elevation and outcomes was assessed using adjusted Cox models. RESULTS: 10,432 men and 4,345 women were included. Elevation of hsCRP was present in 25.7% of men and 37.0% of women (p < .01). In men, prevalence of hsCRP elevation was stable across age strata (ptrend  = .42). In women, hsCRP elevation was most prevalent in patients <50 years (44.6%) and decreased stepwise with increasing age (ptrend < .001). After stratifying the population into age quartiles (Q1: <59 years, Q2: 59-66 years, Q3: 67-74 years, Q4: ≥75 years), hsCRP elevation was associated with increased risk of MACE across all age groups in men (HR [95% CI] Q1: 1.49 [1.12-1.98]; Q2: 1.51 [1.21-2.06]; Q3: 1.76 [1.27-2.51]; Q4: 1.43[1.03-1.97]). In women, hsCRP elevation was associated with increased risk of MACE only among older patients (HR [95% CI] Q1: 1.08 [0.64-0.82]; Q2: 1.52 [0.93-2.46]; Q3: 1.65 [1.08-2.50]; Q4: 1.52 [1.02-1.28]). CONCLUSION: Among patients undergoing PCI, prevalence and prognostic value of hsCRP elevation were age-dependent exclusively in women.

1-Year COMBO stent outcomes stratified by the PARIS bleeding prediction score: From the MASCOT registry.

BACKGROUND: The COMBO stent is a biodegradable-polymer sirolimus-eluting stent with endothelial progenitor cell capture technology for faster endothelialization. OBJECTIVE: We analyzed COMBO stent outcomes in relation to bleeding risk using the PARIS bleeding score. METHODS: MASCOT was an international registry of all-comers undergoing attempted COMBO stent implantation. We stratified patients as low bleeding-risk (LBR) for PARIS score ≤ 3 and intermediate-to-high (IHBR) for score > 3 based on baseline age, body mass index, anemia, current smoking, chronic kidney disease and need for triple therapy. Primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a non-target vessel or clinically-driven target lesion revascularization (TLR). Bleeding was adjudicated using the Bleeding Academic Research Consortium (BARC) definition. Dual antiplatelet therapy (DAPT) cessation was independently adjudicated. RESULTS: The study included 56% (n = 1270) LBR and 44% (n = 1009) IHBR patients. Incidence of 1-year TLF was higher in IHBR patients (4.1% vs. 2.6%, p = 0.047) driven by cardiac death (1.7% vs. 0.7%, p = 0.029) with similar rates of MI (1.8% vs. 1.1%, p = 0.17), TLR (1.5% vs. 1.6%, p = 0.89) and definite/ probable stent thrombosis (1.2% vs. 0.6%, p = 0.16). Incidence of 1-year major BARC 3 or 5 bleeding was significantly higher in IHBR patients (2.3% vs. 0.9%, p = 0.0094), as was the incidence of DAPT cessation (29.3% vs. 22.8%, p < 0.01), driven by physician-guided discontinuation. CONCLUSIONS: Patients with intermediate-to-high PARIS bleeding risk in the MASCOT registry experienced greater incidence of 1-year TLF, major bleeding and DAPT cessation than LBR patients, without significant differences in stent thrombosis.

Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes.

AIMS: To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). METHODS AND RESULTS: In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked ∼30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). CONCLUSIONS: Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for ≥8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.