Aficamten: A Breakthrough Therapy for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

Aficamten is a novel cardiac myosin inhibitor that has demonstrated its ability to safely lower left ventricular outflow tract (LVOT) gradients and improve heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). Based on the REDWOOD-HCM open label extension (OLE) study, participants receiving aficamten had significantly reduced resting and Valsalva LVOT gradient within 2 weeks after initiating treatment, with ongoing improvements over 24 weeks, and recent evidence suggests effects can sustain up to 48 weeks. While beta-blockers, calcium channel blockers, and disopyramide have shown some benefits in managing HCM, they have limited direct impact on the underlying disease process in patients with obstructive HCM. Aficamten achieves its therapeutic effect by reducing hypercontractility and improving diastolic function in obstructive HCM. Mavacamten was the first cardiac myosin inhibitor approved for symptomatic obstructive HCM. However, aficamten has a shorter human half-life (t1/2) and fewer drug-drug interactions, making it a preferable treatment option. This review evaluates the long-term clinical value and safety of aficamten in patients with obstructive HCM based on available data from completed and ongoing clinical trials. Additionally, the molecular basis of sarcomere-targeted therapy in reducing LVOT gradients is explored, and its potential in managing obstructive HCM is discussed.

Low-Dose vs Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Trial.

BACKGROUND: Current guidelines recommend a target international normalized ratio (INR) range of 2.5 to 3.5 in patients with a mechanical mitral prosthesis. The Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) Mitral randomized controlled noninferiority trial assessed safety and efficacy of warfarin at doses lower than currently recommended in patients with an On-X (Artivion, Inc) mechanical mitral valve. METHODS: After On-X mechanical mitral valve replacement, followed by at least 3 months of standard anticoagulation, 401 patients at 44 North American centers were randomized to low-dose warfarin (target INR, 2.0-2.5) or standard-dose warfarin (target INR, 2.5-3.5). All patients were prescribed aspirin, 81 mg daily, and encouraged to use home INR testing. The primary end point was the sum of the linearized rates of thromboembolism, valve thrombosis, and bleeding events. The design was based on an expected 7.3% event rate and 1.5% noninferiority margin. RESULTS: Mean patient follow-up was 4.1 years. Mean INR was 2.47 and 2.92 (P <.001) in the low-dose and standard-dose warfarin groups, respectively. Primary end point rates were 11.9% per patient-year in the low-dose group and 12.0% per patient-year in the standard-dose group (difference, -0.07%; 95% CI, -3.40% to 3.26%). The CI >1.5%, thus noninferiority was not achieved. Rates (percentage per patient-year) of the individual components of the primary end point were 2.3% vs 2.5% for thromboembolism, 0.5% vs 0.5% for valve thrombosis, and 9.13% vs 9.04% for bleeding. CONCLUSIONS: Compared with standard-dose warfarin, low-dose warfarin did not achieve noninferiority for the composite primary end point. (PROACT Clinicaltrials.gov number, NCT00291525).

Interhospital failure to rescue after coronary artery bypass grafting.

OBJECTIVE: We evaluated whether interhospital variation in mortality rates for coronary artery bypass grafting was driven by complications and failure to rescue. METHODS: An observational study was conducted among 83,747 patients undergoing isolated coronary artery bypass grafting between July 2011 and June 2017 across 90 hospitals. Failure to rescue was defined as operative mortality among patients developing complications. Complications included the Society of Thoracic Surgeons 5 major complications (stroke, surgical reexploration, deep sternal wound infection, renal failure, prolonged intubation) and a broader set of 19 overall complications. After creating terciles of hospital performance (based on observed:expected mortality), each tercile was compared on the basis of crude rates of (1) major and overall complications, (2) operative mortality, and (3) failure to rescue (among major and overall complications). The correlation between hospital observed and expected (to address confounding) failure to rescue rates was assessed. RESULTS: Median Society of Thoracic Surgeons predicted mortality risk was similar across hospital observed:expected mortality terciles (P = .831). Mortality rates significantly increased across terciles (low tercile: 1.4%, high tercile: 2.8%). Although small in magnitude, rates of major (low tercile: 11.1%, high tercile: 12.2%) and overall (low tercile: 36.6%, high tercile: 35.3%) complications significantly differed across terciles. Nonetheless, failure to rescue rates increased substantially across terciles among patients with major (low tercile: 9.1%, high tercile: 14.3%) and overall (low tercile: 3.3%, high tercile: 6.8%) complications. Hospital observed and expected failure to rescue rates were positively correlated among patients with major (R2 = 0.14) and overall (R2 = 0.51) complications. CONCLUSIONS: The reported interhospital variability in successful rescue after coronary artery bypass grafting supports the importance of identifying best practices at high-performing hospitals, including early recognition and management of complications.

Interhospital variability in failure to rescue rates following aortic valve surgery.

Objective: This study evaluated interhospital variability and determinants of failure-to-rescue for patients undergoing surgical aortic valve replacement. Methods: An observational study was conducted among 28,842 patients undergoing aortic valve replacement with or without coronary artery bypass grafting between July 2011 and June 2017 across 90 hospitals participating in the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Postoperative complications were defined as major (stroke, renal failure, reoperation, prolonged ventilation, sternal infection) and overall (major plus 14 other morbidities). Hospital terciles of observed to expected (O/E) mortality were compared on crude rates of major and overall complications, operative mortality, and failure to rescue (among major and overall complications). The correlation between hospital observed and expected failure-to-rescue rates was assessed. Results: Median Society of Thoracic Surgeons Adult Cardiac Surgery Database predicted mortality risk was similar across hospital O:E mortality terciles (P = .10). As expected, mortality rates significantly increased across terciles (low O/E tercile: 1.6%, high O/E tercile: 4.7%; P < .001). Failure-to-rescue rates increased substantially across hospital mortality terciles among patients with major (low tercile, 8.8% and high tercile, 20.8%) and overall (low tercile, 3.0% and high tercile, 8.9%) complications. Hospital-level expected failure to rescue had a higher correlation with observed complications for overall complications (R2 = 0.71) compared with Society of Thoracic Surgeons major complications (R2 = 0.24). Conclusions: Considerable interhospital variation exists in failure-to-rescue rates following aortic valve replacement. Hospitals in the low O/E mortality tercile experience failure to rescue nearly one-third less than those in the high O/E mortality tercile. Efforts to advance quality will benefit from identifying and disseminating optimal rescue strategies in this patient population.

Mid-term outcomes of concomitant Cox-Maze IV: Results from a multicenter prospective registry.

BACKGROUND: Benefits of concomitant atrial fibrillation (AF) surgical treatment are well established. Cardiac societies support treating AF during cardiac surgery with a class I recommendation. Despite these guidelines, adoption has been inconsistent. We report results of routine performance of concomitant Cox-Maze IV (CMIV) from participating centers using a standardized, prospective registry. METHODS: Nine surgeons at four cardiac surgery programs enrolled 807 patients undergoing concomitant CMIV surgery over 12 years. Lesions were created using bipolar radiofrequency clamps and cryoablation probes. Follow-up occurred at 3- and 6-months, then annually for 3 years. Freedom from AF was defined as no episode >30 s of atrial arrhythmia. RESULTS: Sixty-four percent of patients were male, mean age 69 years, mean left atrial size 4.6 cm, mean preoperative AF duration 4.0 years, mean EuroSCORE 6.4, and mean CHADS2 score 3.1. Thirty-day postoperative mortality and neurologic event rates were 3.3% and 1.3%, respectively. New pacemaker implant rate was 6.3%. Freedom from AF rates at 1- and 3-years stratified by preoperative AF type were: paroxysmal 94.6% and 87.5%, persistent 82.1% and 81.9%, and longstanding persistent 84.1% and 78.1%. At 3-year follow up, 84% of patients were off antiarrhythmic drugs and 74% of sinus rhythm patients were off oral anticoagulants. CONCLUSIONS: Routine CMIV is safe and effective. Acceptable outcomes can be achieved across multiple centers and multiple operators even in a moderate risk patient population undergoing more complex procedures. Surgeons and institutions should be encouraged by all cardiac societies to adopt the CMIV procedure to maximize patient benefit.

Temporal trends and predictors of surgical ablation for atrial fibrillation across a multistate healthcare system.

BACKGROUND: Multiple class I and class IIa recommendations exist related to surgical ablation (SA) of atrial fibrillation (AF) in patients undergoing cardiac surgery. OBJECTIVE: Examine temporal trends and predictors of SA for AF in a large US healthcare system. METHODS: We retrospectively analyzed data from the Society for Thoracic Surgery (STS) Adult Cardiac Surgery Database for 21 hospitals in the Providence St. Joseph Health system. All patients with preoperative AF who underwent isolated coronary artery bypass graft (CABG) surgery, isolated aortic valve replacement (AVR), AVR with CABG surgery (AVR+CABG), isolated mitral valve repair or replacement (MVRr), and MVRr with CABG surgery (MVRr+CABG) from July 1, 2014, to March 31, 2020 were included. Temporal trends in SA were evaluated using the Cochran-Armitage trends test. A multilevel logistic regression model was used to examine patient-, hospital-, and surgeon-level predictors of SA. RESULTS: Among 3124 patients with preoperative AF, 910 (29.1%) underwent SA. This was performed most often in those undergoing isolated MVRr (n = 324, 44.8%) or MVRr+CABG (n = 75, 35.2%). Rates of SA increased over time and were highly variable between hospitals. Years since graduation from medical school for the primary operator was one of the few predictors of SA: odds ratio (95% confidence interval) = 0.71 (0.56-0.90) for every 10-year increase. Annual surgical (both hospital and operator) and AF catheter ablation volumes were not predictive of SA. CONCLUSION: Wide variability in rates of SA for AF exist, underscoring the need for greater preoperative collaboration between cardiologists, electrophysiologists, and cardiac surgeons.

WITHDRAWN: Low-Dose Versus Standard Warfarin After Mechanical Mitral Valve Replacement: A Randomized Controlled Trial.

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A Reproducible and Effective Technique for Coronary Sinus Injury Repair.

Objective: Coronary sinus injury related to the use of a retrograde cardioplegia catheter is a rare but potentially life-threatening complication with mortality reported as high as 20%. We present a series of iatrogenic coronary sinus injuries as well as an effective method of repair without any ensuing mortality. Methods: There were 3,004 cases that utilized retrograde cardioplegia at our institution from 2007 to 2018. Of these, 15 patients suffered a coronary sinus injury, an incidence of 0.49%. A pericardial roof repair was performed in 14 cases in which autologous pericardium was sutured circumferentially to normal epicardium around the injury with purified bovine serum albumin and glutaraldehyde injected into the newly created space as a sealant. Incidence of perioperative morbidity and mortality, operative time, and length of stay were collected. Results: In our series, there were no intraoperative or perioperative mortalities. Procedure types included coronary artery bypass grafting (CABG), valve replacement and repair, or combined CABG and valve procedures. Median (interquartile range) cross-clamp time was 100 (88 to 131) minutes, cardiopulmonary bypass duration was 133 (114 to 176) minutes, and length of stay was 6 (4 to 8) days. None of the patients returned to the operating room for hemorrhage, and there were no complications associated with the repair of a coronary sinus injury when using the pericardial roof technique. Conclusions: Coronary sinus injuries can result in difficult to manage perioperative bleeding and potentially lethal consequences from cardiac manipulation. Our series supports the pericardial roof technique as an effective solution to a challenging intraoperative complication.

Cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Temporal Trends in Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting: Insights From the Washington Cardiac Care Outcomes Assessment Program.

Background Patient selection and outcomes for percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) have changed over the past decade. However, there is limited information on outcomes for both revascularization strategies in the same population. The study evaluated temporal changes in risk profile, procedural characteristics, and clinical outcomes for PCI- and CABG-treated patients. Methods and Results We analyzed all PCI and isolated CABG between 2005 and 2017 in nonfederal hospitals in Washington State. Descriptive analysis was performed to evaluate temporal changes in risk profile and, risk-adjusted in-hospital mortality. Over the study period, 178 474 PCI and 36 592 CABG procedures were performed. PCI and CABG volume decreased by 2.9% and 22.6%, respectively. Compared with 2005-2009, patients receiving either form of revascularization between 2014 and 2017 had a higher prevalence of comorbidities including diabetes mellitus and hypertension and dialysis. Presentation with ST-segment-elevation myocardial infarction (17% versus 20%) and cardiogenic shock (2.4% versus 3.4%) increased for patients with PCI compared with CABG. Conversely, clinical acuity decreased for patients receiving CABG over the study period. From 2005 to 2017, mean National Cardiovascular Data Registry CathPCI mortality score increased for patients treated with PCI (20.1 versus 22.4, P<0.0001) and decreased for patients treated with CABG (18.8 versus 17.8, P<0.0001). Adjusted observed/expected in-hospital mortality ratio increased for PCI (0.98 versus 1.19, P<0.0001) but decreased for CABG (1.21 versus 0.74, P<0.0001) over the study period. Conclusions Clinical acuity increased for patients treated with PCI rather than CABG. This resulted in an increase in adjusted observed/expected mortality ratio for patients undergoing PCI and a decrease for CABG. These shifts may reflect an increased use of PCI instead of CABG for patients considered to be at high surgical risk.

Intrathoracic complications associated with trans-femoral transcatheter aortic valve replacement: Implications for emergency surgical preparedness.

BACKGROUND: Intrathoracic complications (ITC) requiring emergency surgical intervention occur during transcatheter aortic valve replacement (TAVR). OBJECTIVES: Characterize the incidence, outcomes and predictors of ITC in a large cohort of transfemoral (TF) TAVR cases over a 5 year period. METHODS: Retrospective registry and chart review of all nonclinical trial TF-TAVR patients from seven centers within one hospital system from 2012-2016. ITC were defined as cardiac perforation, new or worsening pericardial effusion/tamponade, annular rupture, thoracic aortic injury, aortic valve dislodgement, and coronary artery occlusion. Procedural and 30-day outcomes and 1-year mortality were compared between ITC and no ITC patients. Multivariable logistic regression was used to identify predictors of ITC. RESULTS: Over the study period, 1,581 patients had TF-TAVR and 68 ITC occurred in 46 patients (2.9%). The most common ITCs were pericardial effusion/tamponade (59%), cardiac perforation (33%), and valve dislodgement (33%). ITC rate did not decline over time (rate (95% confidence interval) for 2012 = 0% (0-8.8%), 2013 = 1.3% (0-7.2%), 2014 = 4.4% (2.2-8.0%), 2015 = 3.5% (2.0-5.6%), and 2016 = 2.4% (1.5-3.8%)). ITC patients had worse 1-year survival (ITC: 60.7% (45.1-73.1%), no ITC: 88.7% (87.0-90.3%); p < .001). The majority of ITC patient deaths occurred within the first 30 days. Multivariable models to predict ITC were not successful. CONCLUSIONS: ITC did not decline over time in our cohort. Predictors of ITC could not be identified. While these events are rare, they are associated with worse procedural outcomes and mortality. Heart teams should continue to be prepared for emergency intervention.