Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation.

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).

Non-vitamin K antagonist oral anticoagulants in patients with valvular heart disease.

The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban have transformed the management of atrial fibrillation (AF), but are only approved by regulatory authorities for stroke prophylaxis in patients with so-called "non-valvular AF." This terminology has spawned confusion about which patients with valvular heart disease benefit from NOACs and which should be treated with vitamin K antagonists (VKAs) instead. Patients with valvular heart disease other than mechanical prosthetic valves or severe mitral stenosis (including those with bioprosthetic valves) were included in pivotal trials demonstrating the benefit of NOACs over VKAs, and consensus guidelines recommend NOACs over VKAs in these patients. Subsequent devoted randomized controlled trials in patients with AF and bioprosthetic valves, including transcatheter valves, have confirmed the safety of NOACs in this population. In patients with rheumatic mitral stenosis, observational studies indicate that NOACs may be safe and effective, but randomized controlled trials are ongoing. By contrast, a randomized controlled trial showed that dabigatran is harmful in patients with mechanical prosthetic mitral valves; however, these data may not extrapolate to patients with mechanical valve prostheses in other locations or to other NOACs, and randomized controlled trials are ongoing. In this review, we discuss these data in greater depth, and make recommendations for the use of NOACs in patients with valvular heart disease.

Risk/Benefit Tradeoff of Antithrombotic Therapy in Patients With Atrial Fibrillation Early and Late After an Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From AUGUSTUS.

BACKGROUND: In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo. METHODS: In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y12 inhibitor were randomized to blinded aspirin or placebo and to open-label apixaban or VKA for 6 months. In a post hoc analysis, we compared the risk of 3 composite bleeding outcomes and 3 composite ischemic outcomes from randomization through 30 days and from 30 days to 6 months with apixaban and VKA and with aspirin and placebo. RESULTS: Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23-1.70]) and fewer severe ischemic events (absolute risk difference, -0.91% [95% CI, -1.74 to -0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23-2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, -0.17% [95% CI, -1.33 to 0.98]). CONCLUSIONS: In patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention receiving a P2Y12 inhibitor, apixaban is preferred over VKA. Use of aspirin immediately and for up to 30 days results in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events. After 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events. These results inform shared, patient-centric decision making on the ideal duration of the use of aspirin after an acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation receiving oral anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Transcatheter aortic valve replacement associated infective endocarditis case series: broadening the criteria for diagnosis is the need of the hour.

BACKGROUND: Transcatheter valve replacement (TAVR) is an important therapeutic intervention for patients with aortic valve stenosis. As TAVR has become available to a broader population, there has been an increase in the number of less common, yet potentially catastrophic, complications. TAVR related infective endocarditis (TAVR-IE) is a rare, but potentially fatal, complication. CASE SERIES: We present here two patients that we encountered for TAVR associated infective endocarditis. Our first patient presented 5 weeks after his TAVR. His initial presentation was consistent with signs of sepsis. The patient then developed Mobitz type I block during hospital course. His TEE was negative for features of infective endocarditis. Due to high suspicion, patient was taken for surgical exploration and was found to have multiple foci of vegetation adhered to the stent frame. Our second patient presented with new onset pulmonary edema, worsening heart failure and systemic inflammatory response. A TEE was done for persistent MSSA bacteremia which showed stable prosthetic valve function with no signs of infective endocarditis. Patient was discharged with a prolonged course of intravenous antibiotics. Patient was re-admitted for worsening sepsis and blood cultures were positive for MSSA. Patient was taken for surgical exploration of his prosthetic aortic valve which showed purulent aortic root abscess. CONCLUSION: Through these cases, we aim to raise awareness on TAVR-IE. Due to the atypical clinical presentation, the modified Duke criteria may not be sufficient to diagnose TAVR-IE. Transesophageal echocardiogram in TAVR-IE may be negative or indeterminate. Prosthetic valve shadow may obscure smaller vegetations and/or smaller abscesses. A negative transesophageal echocardiogram should not rule out TAVR-IE and further diagnostic imaging modalities should be considered. PET/CT after administration of 18F-FDG (fluorodeoxyglucose) is a useful diagnostic tool in the diagnosis of infective endocarditis where TEE has been negative or inconclusive. Multi-modal imaging, in addition to the modified Duke criteria, can facilitate early diagnosis and improved mortality outcomes.

Hospital participation in clinical trials for patients with acute myocardial infarction: Results from the National Cardiovascular Data Registry.

BACKGROUND: Little is known about the proportion of hospitals in the United States that offer clinical trial enrollment opportunities and how patient outcomes differ between hospitals that do and do not participate in clinical trials. METHODS: In the nationwide Chest Pain-MI registry, we described the proportion of hospitals that enrolled patients with acute myocardial infarction (MI) in clinical trials from 2009 to 2014. Hospital-level adherence to every eligible MI performance measure was compared between hospitals that did and did not enroll patients in clinical trials. Using linked Medicare data, we also compared 1-year major adverse cardiovascular events (MACE: death, MI, heart failure, or stroke) among patients ≥65 years old treated at trial versus nontrial hospitals. RESULTS: Among 766 hospitals, 430 (56.1%) enrolled ≥1 MI patient in a clinical trial during the study period, but the proportion of hospitals enrolling patients in clinical trials declined from 36.8% in 2009 to 26.6% in 2014. Complete adherence to performance measures was delivered to a greater proportion of patients at trial hospitals than nontrial hospitals (72.6% vs 64.9%, P < .001; adjusted OR 1.07, 95% CI 1.03-1.12). One-year MACE rates were also lower for trial hospitals (adjusted HR 0.96, 95% CI 0.93-0.99). CONCLUSIONS: Hospitals are becoming less likely to engage in clinical trials for patients with MI. Patients admitted to hospitals that participated in clinical trials more often received guideline-adherent care and had better long-term outcomes.

First-in-human experience with Aortix intraaortic pump.

BACKGROUND: There are limited options for percutaneous mechanical circulatory support (pMCS) in patients requiring high-risk percutaneous coronary intervention. OBJECTIVES: This first-in-human, single-center study aimed to evaluate the safety and feasibility of a novel pMCS device in high-risk percutaneous coronary intervention patients. METHODS: Aortix (Procyrion, Houston, Texas) is a pMCS device deployed in the descending aorta via the femoral artery that uses axial flow to provide cardiac unloading and augment renal and systemic perfusion. We assessed the use and effect of the Aortix device in six patients undergoing high-risk PCI. All patients had impaired left ventricular function, complex coronary disease, renal dysfunction, and suitable iliofemoral anatomy for Aortix placement via transfemoral approach. We recorded periprocedural events including hemodynamic effects of the device on cardiac output and urine output. We then followed patients up to 30 days following the PCI procedure for adverse events. RESULTS: Aortix delivery (18 Fr sheath) took 4-9 min, mean support time was 70 (range 47-95) min, and mean flow rate through the device was 3.5 L/min. During support, mean rate of urine output increased 10-fold (range 2.5-25.0x). Estimated GFR improved at discharge compared with baseline (mean increase 6.95 ± 8.09 mL/min). There were no device failures and PCI was successful in all patients. Aortix was removed and hemostasis was achieved with a vascular closure device and manual pressure. No patients experienced adverse events or hemodynamic compromise. No clinically significant hemolysis occurred (mean LDH 239.2 ± 73.6 mU/mL at baseline and 206.4 ± 82.2 mU/mL at discharge). No vascular access complications were observed. CONCLUSIONS: Aortix, a novel pMCS device, was successfully deployed and retrieved in all initial patients undergoing high-risk PCI. We noted no significant hemolysis with temporary use of this axial flow device. Improvement in eGFR suggests a potential renal protective effect and is an important area for future investigation in patients with impaired left ventricular function and renal dysfunction.

Should All Low-risk Patients Now Be Considered for TAVR? Operative Risk, Clinical, and Anatomic Considerations.

PURPOSE OF REVIEW: This article reviews the current data on TAVR in low-risk patients with severe, symptomatic aortic stenosis, highlights the results of the recently published Medtronic Low Risk Randomized Study and PARTNER 3 trials, and describes specific clinical, anatomic, and procedural considerations regarding the optimal treatment choice in this population. RECENT FINDINGS: In low-risk patients, the Medtronic Low Risk Randomized Study demonstrated TAVR to be non-inferior to surgery with respect to the composite endpoint of death or disabling stroke while PARTNER 3 trial proved TAVR to be superior to surgery with regard to the composite endpoint of death, stroke, or rehospitalization. Recent trials demonstrate the safety and efficacy of TAVR in low-risk patients and have led to an FDA indication for the use of TAVR in these patients. However, the lack of long-term data on the rate of transcatheter valve deterioration in the younger population, higher incidence of paravalvular leak and pacemaker implantation following TAVR, along with certain intrinsic anatomic factors remain potential challenges to generalize TAVR in all low surgical risk patients. We describe specific clinical, anatomic, and procedural considerations regarding the optimal treatment choice for low-risk patients with severe, symptomatic AS.

An open-Label, 2 × 2 factorial, randomized controlled trial to evaluate the safety of apixaban vs. vitamin K antagonist and aspirin vs. placebo in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention: Rationale and design of the AUGUSTUS trial.

BACKGROUND: The optimal antithrombotic strategy for patients with atrial fibrillation (AF) who develop acute coronary syndrome (ACS) and/or the need for percutaneous coronary intervention (PCI) is uncertain. The risk of bleeding is a major concern when oral anticoagulation is required to prevent stroke, and concomitant therapy with antiplatelet agents is required to minimize recurrent ischemic events. DESIGN: AUGUSTUS is an international, multicenter randomized trial with a 2 × 2 factorial design to compare apixaban with vitamin K antagonists and aspirin with placebo in patients with AF who develop ACS and/or undergo PCI and are receiving a P2Y12 inhibitor. Patients will be evaluated for eligibility during their ACS and/or PCI hospitalization. The primary outcome is the composite of major and clinically relevant nonmajor bleeding defined by the International Society on Thrombosis and Haemostasis. A key secondary outcome is the composite of all-cause death and all-cause hospitalization. Other secondary objectives are to evaluate ischemic outcomes including the composite of death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and all-cause hospitalization and each individual component. The aim is to enroll approximately 4,600 patients from around 500 sites in 33 countries. SUMMARY: AUGUSTUS will provide insight into the optimal oral antithrombotic therapy strategy for patients with AF and concomitant coronary artery disease. The unique 2 × 2 factorial design will delineate the bleeding effects of various anticoagulant and antiplatelet therapies and generate evidence to guide the selection of the optimal antithrombotic regimen for this challenging group of patients. It is the largest and only prospective randomized trial to investigate in a blinded fashion the risk and benefits of aspirin on top of a non-vitamin K antagonist oral anticoagulant and P2Y12 receptor inhibition.

Variation in post-TAVR antiplatelet therapy utilization and associated outcomes: Insights from the STS/ACC TVT Registry.

BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended following transcatheter aortic valve replacement (TAVR); however, the optimal antiplatelet strategy is undefined, and little is known about practice patterns. We aimed to describe contemporary practice patterns of antiplatelet therapy and their relationship to outcomes post-TAVR. METHODS: The population was derived from the National Cardiovascular Data Registry, Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry with Center for Medical Services linkage for 1-year outcomes from October 1, 2011 to June 30,2016. The primary outcome measured was DAPT use in patients without anticoagulation. Secondary outcomes included death, major bleeding, myocardial infarction (MI), and stroke at 1 year. RESULTS: Overall, 16,694 patients underwent transfemoral TAVR at 444 hospitals and were discharged without anticoagulation. Among these, 13,546 (81.1%) patients were discharged on DAPT, whereas 3,148 patients (18.9%) were discharged on monotherapy. Patients discharged on DAPT versus monotherapy were similar in age, sex, and most comorbid illnesses but had higher rates of coronary artery disease (64.6% vs 52.3%; P < .01) and peripheral artery disease (25.2% vs 22.3%; P < .01). Hospital prescribing patterns varied significantly (median frequency of DAPT 85.7%, interquartile range 94.1%-74.2%). DAPT (vs monotherapy) patients had a similar mortality risk at 1 year (adjusted hazard ratio 0.92, 95% CI 0.81-1.05), significantly higher risk for major bleeding (1.48, 1.10-1.99), and similar hazard for stroke (1.04, 0.83-1.31) and MI (1.00, 0.72-1.39). CONCLUSIONS: In the United States, most patients were discharged on DAPT following TAVR. Practice patterns varied significantly among hospitals. Patients discharged with DAPT had a similar adjusted risk of mortality, stroke, and MI compared to antiplatelet monotherapy, although risk for bleeding was significantly higher. Future investigation is needed to define the optimal antiplatelet therapy for patients undergoing TAVR.

Challenges in Aortic Stenosis: Review of Antiplatelet/Anticoagulant Therapy Management with Transcatheter Aortic Valve Replacement (TAVR): TAVR with Recent PCI, TAVR in the Patient with Atrial Fibrillation, and TAVR Thrombosis Management.

PURPOSE OF REVIEW: This review aims to describe the current evidence and consensus recommendations around antiplatelet and anticoagulant management in three common clinical scenarios in transcatheter aortic valve replacement (TAVR): (1) recent percutaneous coronary intervention (PCI) preceding TAVR, (2) atrial fibrillation (AF) management in patients undergoing TAVR, and (3) bioprosthetic valve thrombosis management in TAVR. RECENT FINDINGS: Several small clinical trials have evaluated the use of single vs. dual antiplatelet therapy in patients undergoing TAVR, with most recent data favoring single antiplatelet therapy. There are several trials currently enrolling and in follow-up that evaluate the use of anticoagulants in combination with single and dual antiplatelet therapy for patients with AF undergoing TAVR, but as yet, there is no data to support a clear strategy. The use of DAPT after PCI continues to potentially shorten in patients undergoing elective PCI, thus prolonged DAPT may not be necessary post TAVR for the sake of PCI. Bioprosthetic valve thrombosis occurs more commonly than previously thought, but has uncertain clinical significance. In observational studies, antiplatelet therapy has little effect on bioprosthetic valve thrombosis, whereas anticoagulation is effective in both prevention and treatment of thrombosis. DAPT is currently recommended for 1-6 months for all patients without an indication for oral anticoagulation who undergo TAVR; however, there is a growing amount of evidence for single antiplatelet therapy. In the special situation of patients who have recently undergone PCI, the length of DAPT will depend on stent selection (BMS vs. DES), but may not be significantly prolonged unless the patient experienced an acute coronary syndrome prior to TAVR. There is no clear, optimal antithrombotic strategy for patients with AF who undergo TAVR, but avoidance of triple therapy by using OAC and low-dose ASA seems to be reasonable. OAC, not DAPT, is now known to prevent bioprosthetic valve thrombosis in TAVR and SAVR patients; however, the optimal therapy remains unknown. For patients who develop bioprosthetic valve thrombosis, OAC for 3-6 months, and repeat imaging is recommended to document resolution.

Data monitoring committees: Promoting best practices to address emerging challenges.

BACKGROUND AND PURPOSE: Data monitoring committees are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of data monitoring committees from sponsors and investigators is essential in achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten data monitoring committees' independence and effectiveness. METHODS: An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary data monitoring committees. RESULTS AND CONCLUSIONS: Prospective data monitoring committee members need better training. Options could include didactic instruction as well as apprenticeships to provide real-world experience. Data monitoring committee members should be protected against legal liability arising from their service. While avoiding breaches in confidentiality of interim data remains a high priority, data monitoring committees should have access to unblinded efficacy and safety data throughout the trial to enable informed judgments about risks and benefits. Because overly rigid procedures can compromise their independence, data monitoring committees should have the flexibility necessary to best fulfill their responsibilities. Data monitoring committee charters should articulate principles that guide the data monitoring committee process rather than list a rigid set of requirements. Data monitoring committees should develop their recommendations by consensus rather than through voting processes. The format for the meetings of the data monitoring committee should maintain the committee's independence and clearly establish the leadership of the data monitoring committee chair. The independent statistical group at the Statistical Data Analysis Center should have sufficient depth of knowledge about the study at hand and experience with trials in general to ensure that the data monitoring committee has access to timely, reliable, and readily interpretable insights about emerging evidence in the clinical trial. Contracts engaging data monitoring committee members for industry-sponsored trials should have language customized to the unique responsibilities of data monitoring committee members rather than use language appropriate to consultants for product development. Regulatory scientists would benefit from experiencing data monitoring committee service that does not conflict with their regulatory responsibilities.

Aortic valve surgery and survival in patients with moderate or severe aortic stenosis and left ventricular dysfunction.

AIMS: We aimed to determine the frequency of aortic valve surgery (AVR) with or without coronary artery bypass grafting (CABG), among patients with moderate/severe aortic stenosis (AS) and left ventricular systolic dysfunction (LVSD), and its relationship with survival. METHODS AND RESULTS: The Duke Echocardiographic Database (N = 132 804) was queried for patients with mean gradient ≥25 mmHg and/or peak velocity ≥3 m/s and LVSD (left ventricular ejection fraction ≤50%) from 1 January 1995-28 February 2014. For analyses purposes, AS was defined both by mean gradient and calculated aortic valve area (AVA) criteria. Time-dependent indicators of AVR in multivariable Cox models were used to assess the relationship of AVR and all-cause mortality. A total of 1634 patients had moderate (N = 1090, 67%) or severe (N = 544, 33%) AS by mean gradient criteria. Overall, 287 (26%) patients with moderate AS and 263 (48%) patients with severe AS underwent AVR within 5 years of the qualifying echo. There were 863 (53%) deaths observed up to 5 years following index echo. After multivariable adjustment in an inverse probability weighted regression model, AVR was associated with higher 5-year survival amongst patients with moderate AS and severe AS whether classified by AVA or mean gradient criteria. Over all, AVR ± CABG compared with medical therapy was associated with significantly lower mortality [hazard ratio, HR = 0.49 (0.38, 0.62), P < 0.0001]. Compared with CABG alone, CABG + AVR was associated with better survival [HR = 0.18 (0.12, 0.27), P < 0.0001]. CONCLUSIONS: In patients with moderate/severe AS and LVSD, mortality is substantial and amongst those selected for surgery, AVR with or without CABG is associated with higher survival. Research is required to understand factors contributing to current practice patterns and the possible utility of transcatheter approaches in this high-risk cohort.

Long-term outcomes associated with hospital acquired thrombocytopenia among patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Acquired thrombocytopenia after a non-ST-segment-elevation-acute coronary syndrome (NSTE-ACS) has been associated with increased in-hospital mortality and hemorrhagic complications, but longer term outcomes are unclear. We examined the association between thrombocytopenia and long-term outcomes after accounting for thrombocytopenia severity and discharge medication use. METHODS: Data from 7,435 NSTE-ACS patients enrolled in the SYNERGY trial were analyzed. Severe thrombocytopenia was defined as a nadir platelet count <100 × 10(9)/L or a ≥ 50% drop from baseline. Mild thrombocytopenia was defined as a nadir platelet count between 100 and 149 × 10(9)/L with a <50% drop from baseline. The primary outcomes of interest were in-hospital GUSTO moderate-severe bleeding and 1-year mortality. RESULTS: Overall, 675 patients (9.1%) developed mild thrombocytopenia and 139 patients (1.9%) developed severe thrombocytopenia. In-hospital bleeding risks were higher in patients with mild (7.7%, adjusted HR 1.63, 95% CI 1.16-2.29) or severe (28.2%, adjusted HR 6.93, 95% CI 4.55-10.56) thrombocytopenia than in patients without thrombocytopenia (5.2%). One-year mortality rates were 6.5%, 8.1%, and 28.1% among patients with no, mild, and severe thrombocytopenia, respectively (log rank P < 0.001) but only severe thrombocytopenia remained significantly associated with increased mortality after adjustment: HR 4.07, 95% CI 2.86-5.78. Patients who developed severe thrombocytopenia were less likely to be discharged on guideline-recommended antiplatelet therapy. The relationship between severe thrombocytopenia and mortality was attenuated by but persisted after adjusting for discharge medication use (HR 2.83, 95% CI 1.49-5.38). CONCLUSIONS: Thrombocytopenia occurs commonly during the course of NSTE-ACS care; even mild decreases are associated with clinically meaningful bleeding. Patients who developed severe thrombocytopenia were less likely to be discharged on guideline-recommended antiplatelet therapy; this may contribute to their higher associated long-term mortality.

Treatment of mechanical aortic valve thrombosis with heparin and eptifibatide.

A 75-year old woman with a history of coronary disease status post 3-vessel coronary artery bypass grafting (CABG) 8 years ago and a repeat one-vessel CABG 2 years ago in the setting of aortic valve replacement with a #19 mm St. Jude bileaflet mechanical valve for severe aortic stenosis presented with two to three weeks of progressive dyspnea and increasing substernal chest discomfort. Echocardiography revealed a gradient to 31 mmHg across her aortic valve, increased from a baseline of 13 mmHg five months previously. Fluoroscopy revealed thrombosis of her mechanical aortic valve. She was not a candidate for surgery given her multiple comorbidities, and fibrinolysis was contraindicated given a recent subdural hematoma 1 year prior to presentation. She was treated with heparin and eptifibatide and subsequently demonstrated resolution of her aortic valve thrombosis. We report the first described successful use of eptifibatide in addition to unfractionated heparin for the management of subacute valve thrombosis in a patient at high risk for repeat surgery or fibrinolysis.

Predictors of Disease Progression and Adverse Clinical Outcomes in Patients With Moderate Aortic Stenosis Using an Artificial Intelligence-Based Software Platform.

Patients with moderate aortic stenosis (AS) have a greater risk of adverse clinical outcomes than that of the general population. How this risk compares with those with severe AS, along with factors associated with outcomes and disease progression, is less clear. We analyzed serial echoes (from 2017 to 2019) from a single healthcare system using Tempus Next (Chicago, Illinois) software. AS severity was defined according to American Heart Association/American College of Cardiology guidelines. Outcomes of interest included death or heart failure hospitalization. We used Cox proportional hazards models and logistic regression to identify predictors of clinical outcome and disease progression, respectively. From 82,805 echoes for 61,546 patients, 1,770; 914; 565; and 1,463 patients had no, mild, moderate, or severe AS, respectively. Both patients with moderate and those with severe AS experienced a similar prevalence of adverse clinical outcomes (p = 0.45) that was significantly greater than that of patients without AS (p <0.01). In patients with moderate AS, atrial fibrillation (hazard ratio 3.29, 95% confidence interval 1.79 to 6.02, p <0.001) and end-stage renal disease (hazard ratio 3.34, 95% confidence interval 1.87 to 5.95, p <0.001) were associated with adverse clinical outcomes. One-third of patients with moderate AS with a subsequent echo (139/434) progressed to severe AS within 1 year. In conclusion, patients with moderate AS can progress rapidly to severe AS and experience a similar risk of adverse clinical outcomes; predictors include atrial fibrillation and low left ventricular ejection fraction. Machine learning algorithms may help identify these patients. Whether these patients may warrant earlier intervention merits further study.

National Variability in Pacemaker Implantation Rate Following TAVR: Insights From the STS/ACC TVT Registry.

BACKGROUND: Although permanent pacemaker (PPM) implantation is a common complication of transcatheter aortic valve replacement (TAVR), hospital variation and change in PPM implantation rates are ill defined. OBJECTIVES: The aim of this study was to determine hospital-level variation and temporal trends in the rate of PPM implantation following TAVR. METHODS: Using the American College of Cardiology/Society of Thoracic Surgeons TVT (Transcatheter Valve Therapy) Registry, temporal changes in variation of in-hospital and 30-day PPM implantation were determined among 184,452 TAVR procedures across 653 sites performed from 2016 to 2020. The variation in PPM implantation adjusted for valve type by annualized TAVR volume was determined, and characteristics of sites below, within, and above the 95% boundary were identified. A series of stepwise multivariable hierarchical models were then fit, and the median OR was used to measure variation in pacemaker rates among sites. RESULTS: From 2016 to 2020, the overall rate of PPM implantation was 11.3%, with wide variation across sites (range: 0%-36.4%); rates trended lower over time. Adjusted for annualized volume, there were 34 sites with PPM implantation rates above the 95th percentile CI and 28 with rates below, with wide variation among the remaining sites. After adjusting for patient-level covariates, there was variation among sites in the probability of PPM implantation (median OR: 1.39; 95% CI: 1.35-1.43, P < 0.001); although some of the variation was explained by the addition of valve type, residual variation in PPM implantation rates persisted in additional models incorporating site-level covariates (annualized volume, region, teaching status, hospital beds, etc). CONCLUSIONS: Although PPM implantation rates have decreased over time, substantial site-level variation remains even after accounting for observed patient characteristics and site-level factors. As there are numerous outlier sites both above and below the 95% confidence limit, dissemination of best practices from high-performing sites to low-performing sites and guideline-based education may be important quality improvement initiatives to reduce rates of this common complication.

A Multimodality Video-Based AI Biomarker For Aortic Stenosis Development And Progression.

Importance: Aortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up. Objective: A video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler. Here, we deploy DASSi to patients with no or mild/moderate AS at baseline to identify AS development and progression. Design Setting and Participants: We defined two cohorts of patients without severe AS undergoing echocardiography in the Yale-New Haven Health System (YNHHS) (2015-2021, 4.1[IQR:2.4-5.4] follow-up years) and Cedars-Sinai Medical Center (CSMC) (2018-2019, 3.4[IQR:2.8-3.9] follow-up years). We further developed a novel computational pipeline for the cross-modality translation of DASSi into cardiac magnetic resonance (CMR) imaging in the UK Biobank (2.5[IQR:1.6-3.9] follow-up years). Analyses were performed between August 2023-February 2024. Exposure: DASSi (range: 0-1) derived from AI applied to echocardiography and CMR videos. Main Outcomes and Measures: Annualized change in peak aortic valve velocity (AV-Vmax) and late (>6 months) aortic valve replacement (AVR). Results: A total of 12,599 participants were included in the echocardiographic study (YNHHS: n=8,798, median age of 71 [IQR (interquartile range):60-80] years, 4250 [48.3%] women, and CSMC: n=3,801, 67 [IQR:54-78] years, 1685 [44.3%] women). Higher baseline DASSi was associated with faster progression in AV-Vmax (per 0.1 DASSi increments: YNHHS: +0.033 m/s/year [95%CI:0.028-0.038], n=5,483, and CSMC: +0.082 m/s/year [0.053-0.111], n=1,292), with levels ≥ vs <0.2 linked to a 4-to-5-fold higher AVR risk (715 events in YNHHS; adj.HR 4.97 [95%CI: 2.71-5.82], 56 events in CSMC: 4.04 [0.92-17.7]), independent of age, sex, ethnicity/race, ejection fraction and AV-Vmax. This was reproduced across 45,474 participants (median age 65 [IQR:59-71] years, 23,559 [51.8%] women) undergoing CMR in the UK Biobank (adj.HR 11.4 [95%CI:2.56-50.60] for DASSi ≥vs<0.2). Saliency maps and phenome-wide association studies supported links with traditional cardiovascular risk factors and diastolic dysfunction. Conclusions and Relevance: In this cohort study of patients without severe AS undergoing echocardiography or CMR imaging, a new AI-based video biomarker is independently associated with AS development and progression, enabling opportunistic risk stratification across cardiovascular imaging modalities as well as potential application on handheld devices.