Balloon-Expandable Valve Geometry After Transcatheter Aortic Valve Replacement in Low-Risk Patients With Bicuspid Versus Tricuspid Aortic Stenosis.

BACKGROUND: Prospective bicuspid low-risk transcatheter aortic valve replacement (TAVR) registries' data demonstrated encouraging short-term results. Detailed data on transcatheter heart valve (THV) geometry after deployment using contemporary devices are lacking. This study sought to examine valve geometry after TAVR in patients with bicuspid aortic stenosis (AS). METHODS: The study population was patients from the LRT (Low Risk TAVR) trial who underwent TAVR using the SAPIEN 3 THV for bicuspid and tricuspid AS. THV geometry measured on 30-day computed tomography (CT) included valve height, angle, depth, and eccentricity. Additionally, THV hemodynamics and outcomes post-TAVR were compared among patients with bicuspid and tricuspid AS. RESULTS: A total of 107 patients from the LRT trial using the SAPIEN 3 THV were included in our analysis. On 30-day CT, the valve height ratio (1.07 vs. 1.07; p = 0.348), depths (right [5.6 mm vs. 6.2 mm; p = 0.223], left [5.3 mm vs. 4.4 mm; p = 0.082] and non [4.8 mm vs. 4.5 mm; p = 0.589] coronary cusps), eccentricities (1.08 vs. 1.07; p = 0.9550), and angles (except the right [3.9 degrees vs. 6.3 degrees; p = 0.003] and left [3.6 degrees vs. 6.0 degrees; p = 0.007]) were similar between bicuspid and tricuspid patients. Hemodynamics, stroke, and mortality were similar at 1 year. CONCLUSION: Despite challenging bicuspid anatomy of the aortic valve, our comprehensive CT analysis supports similar THV geometry between patients with bicuspid and tricuspid AS undergoing TAVR using the SAPIEN 3 THV in low-risk patients. This translated to excellent short-term clinical outcomes and THV hemodynamics in both aortic valve morphologies. TRIAL REGISTRY: NCT02628899, https://clinicaltrials.gov/ct2/show/NCT02628899.

Randomized Trial of Aspirin Versus Warfarin After Transcatheter Aortic Valve Replacement in Low-Risk Patients.

BACKGROUND: The optimal antithrombotic regimen after transcatheter aortic valve replacement remains unclear. METHODS: In this randomized open-label study, low-risk patients undergoing transfemoral transcatheter aortic valve replacement at 7 centers in the United States were randomized 1:1 to low-dose aspirin or warfarin plus low-dose aspirin for 30 days. Patients who could not be randomized were enrolled in a separate registry. Computed tomography or transesophageal echocardiography was performed at 30 days. The primary effectiveness end point was a composite of the following at 30 days: hypoattenuated leaflet thickening, at least moderately reduced leaflet motion, hemodynamic dysfunction (mean aortic valve gradient ≥20 mm Hg, effective orifice area ≤1.0 cm2, dimensionless valve index <0.35, or moderate or severe aortic regurgitation), stroke, or transient ischemic attack. RESULTS: Between July 2018 and October 2019, 94 patients were randomly assigned, 50 to aspirin and 44 to warfarin plus aspirin, and 30 were enrolled into the registry. In the intention-to-treat analysis of the randomized cohort, the composite primary effectiveness end point was met in 26.5% for aspirin versus 7.0% for warfarin plus aspirin (P=0.014; odds ratio, 4.8 [95% CI, 1.3-18.3]). The rate of hypoattenuated leaflet thickening was 16.3% for aspirin versus 4.7% for warfarin plus aspirin (P=0.07; odds ratio, 4.0 [95% CI, 0.8-20.0]). There was no excess bleeding at 30 days with anticoagulation. In the as-treated analysis of pooled randomized and registry cohorts, the rate of hypoattenuated leaflet thickening was 16.7% for aspirin versus 3.1% for warfarin plus aspirin (P=0.011; odds ratio, 6.3 [95% CI, 1.3-30.6]). CONCLUSIONS: In low-risk transcatheter aortic valve replacement patients, anticoagulation with warfarin may prevent transcatheter heart valve dysfunction in the short term without excess bleeding. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03557242.

Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Bicuspid Aortic Valve Stenosis.

OBJECTIVES: The aim of this study was to evaluate clinical outcomes and transcatheter heart valve hemodynamic parameters after transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic stenosis (AS). BACKGROUND: TAVR is approved for low-risk patients in the United States. However, patients with bicuspid AS were excluded from the randomized cohorts of the pivotal low-risk trials. METHODS: The LRT (Low Risk TAVR) trial was an investigator-initiated, prospective, multicenter study and was the first and only U.S. Food and Drug Administration-approved investigational device exemption trial to evaluate the feasibility of TAVR with either balloon-expandable or self-expanding valves in low-risk patients with bicuspid AS. The primary endpoint was all-cause mortality at 30 days. Baseline and follow-up echocardiography and computed tomography to detect leaflet thickening were analyzed in an independent core laboratory. RESULTS: Sixty-one low-risk patients with symptomatic, severe AS and bicuspid aortic valves (78.3% Sievers type 1 morphology) underwent TAVR at 6 centers from 2016 to 2019. The mean age was 68.6 years, and 42.6% were men. At 30 days, there was zero mortality and no disabling strokes. The rate of new permanent pacemaker implantation was 13.1%; just 1 patient had a moderate paravalvular leak at 30 days. Hypoattenuated leaflet thickening was observed in 10% of patients at 30 days. CONCLUSIONS: TAVR appears to be safe in patients with bicuspid AS, with short length of hospital stay, zero mortality, and no disabling strokes at 30 days. Subclinical leaflet thrombosis was observed in a minority of patients at 30 days but did not appear to be associated with clinical events.

Myocardial Protection and Financial Considerations of Custodiol Cardioplegia in Minimally Invasive and Open Valve Surgery.

OBJECTIVE: Single-dose antegrade crystalloid cardioplegia with Custodiol-HTK (histidine-tryptophan-ketoglutarate) has been used for many years. Its safety and efficacy were established in experimental and clinical studies. It is beneficial in complex valve surgery because it provides a long period of myocardial protection with a single dose. Thus, valve procedures (minimally invasive or open) can be performed with limited interruption. The aim of this study is to compare the use of Custodiol-HTK cardioplegia with traditional blood cardioplegia in patients undergoing minimally invasive and open valve surgery. METHODS: A single-institution, retrospective case-control review was performed on patients who underwent valve surgery in Lee Memorial Health System at either HealthPark Medical Center or Gulf Coast Medical Center from July 1, 2011, through March 7, 2015. A total of 181 valve cases (aortic or mitral) performed using Custodiol-HTK cardioplegia were compared with 181 cases performed with traditional blood cardioplegia. Each group had an equal distribution of minimally invasive and open valve cases. Right chest thoracotomy or partial sternotomy was performed on minimally invasive valve cases. Demographics, perioperative data, clinical outcomes, and financial data were collected and analyzed. RESULTS: Patient outcomes were superior in the Custodiol-HTK cardioplegia group for blood transfusion, stroke, and hospital readmission within 30 days (P < 0.05). No statistical differences were observed in the other outcomes categories. Hospital charges were reduced on average by $3013 per patient when using Custodiol-HTK cardioplegia. CONCLUSIONS: Use of Custodiol-HTK cardioplegia is safe and cost-effective when compared with traditional repetitive blood cardioplegia in patients undergoing minimally invasive and open valve surgery.

Acute type a dissection: impact of antegrade cerebral perfusion under moderate hypothermia.

BACKGROUND: The optimal method of arterial cannulation and circulation management for acute type A aortic dissection (type A) remains debated. Moderate hypothermic circulatory arrest (MHCA) and unilateral selective antegrade cerebral perfusion (uSACP) is effective in the elective setting. In this study, the impact of MHCA and uSACP on outcomes for type A repair was evaluated. METHODS: A retrospective review identified 346 patients who underwent type A repair under circulatory arrest, including 193 patients who had MHCA/uSACP. Measured outcomes included operative mortality, permanent neurologic deficit (PND) and temporary neurologic deficit, renal failure, and tracheostomy. Propensity-adjusted, multivariable logistic regression analysis was used to model adverse outcomes. RESULTS: The mean age of MHCA/uSACP patients was 56 years. The mean temperature during MHCA was 26.9 ± 2.0°C. Operative mortality for MHCA/SACP patients was 9.8% compared with 20.3% for the non-MHCA/SACP group (p < 0.01). Propensity score analysis found that MHCA/uSACP did not represent an adverse risk factor for mortality, temporary neurologic deficit, PND, renal failure, or the need for tracheostomy compared with non-MHCA/uSACP techniques. There was a 2.32-fold higher incidence of PND among patients who underwent cross-clamping of the dissected aorta during cooling before circulatory arrest (p < 0.05). CONCLUSIONS: Emergent type A repair can be accomplished with respectable operative risk using MHCA/uSACP. Cross-clamping the dissected aorta before MHCA increases the incidence of PND. These data suggest that MHCA/uSACP represents an effective circulation management strategy for patients undergoing repair of type A and obviates the need for deep hypothermic circulatory arrest.

Ability to induce atrial fibrillation in the peri-operative period is associated with phosphorylation-dependent inhibition of TWIK protein-related acid-sensitive potassium channel 1 (TASK-1).

Peri-operative atrial fibrillation (peri-op AF) is a common complication following thoracic surgery. This arrhythmia is thought to be triggered by an inflammatory response and can be reproduced in various animal models. Previous work has shown that the lipid inflammatory mediator, platelet-activating factor (PAF), synthesized by activated neutrophils, can induce atrial and ventricular arrhythmias as well as repolarization abnormalities in isolated ventricular myocytes. We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. We now demonstrate that canine peri-op AF is associated with the phosphorylation-dependent loss of TASK-1 current. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel. Using a novel phosphorylation site-specific antibody targeting the phosphorylated channel, we have determined that peri-op AF is associated with the loss of TASK-1 current and increased phosphorylation of TASK-1 at this site.

GABAA receptors are expressed and facilitate relaxation in airway smooth muscle.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABA(A)) channels and metabotropic (GABA(B)) receptors. GABA(A) channels are ubiquitously expressed in neuronal tissues, and in mature neurons modulate an inward chloride current resulting in neuronal inhibition due to membrane hyperpolarization. In airway smooth muscle (ASM) cells, membrane hyperpolarization favors smooth muscle relaxation. Although GABA(A) channels and GABA(B) receptors have been functionally identified on peripheral nerves in the lung, GABA(A) channels have never been identified on ASM itself. We detected the mRNA encoding of the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, delta-, gamma(1-3)-, pi-, and theta-subunits in total RNA isolated from native human and guinea pig ASM and from cultured human ASM cells. Selected immunoblots identified the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, and gamma(2)-subunit proteins in native human and guinea pig ASM and cultured human ASM cells. The GABA(A) beta(3)-subunit protein was immunohistochemically localized to ASM in guinea pig tracheal rings. While muscimol, a specific GABA(A) channel agonist, did not affect the magnitude or the time to peak contractile effect of substance P, it directly concentration dependently relaxed a tachykinin-induced contraction in guinea pig tracheal rings, which was inhibited by the GABA(A)-selective antagonist gabazine. Muscimol also relaxed a contraction induced by an alternative contractile agonist histamine. These results demonstrate that functional GABA(A) channels are expressed on ASM and suggest a novel therapeutic target for the relaxation of ASM in diseases such as asthma and chronic obstructive lung disease.

Surgery for myocardial salvage in acute myocardial infarction and acute coronary syndromes.

This article addresses the pathophysiology, the treatment options, and their rationale in the setting of life-threatening acute myocardial infarction and acute on chronic ischemia. Although biases may exist between cardiologists and surgeons, with this review, we hope to provide the reader with information that will shed light on the options that best suit the individual patient in a given set of circumstances.

An overview of energy sources in clinical use for the ablation of atrial fibrillation.

Recent years have seen many developments in the field of alternative energy sources for arrhythmia surgery. The impetus behind these advances is to replace the traditional, "cut-and-sew" Cox maze III procedure with lesion sets that are simpler, shorter, and safer but just as effective. There is demand for technology to make continuous, linear, transmural ablations reliably with a versatile energy source via an epicardial approach. This would make minimally invasive endoscopic surgical ablation of atrial fibrillation (AF) without cardiopulmonary bypass and with a closed chest feasible. These advances would shorten cardio-pulmonary bypass and improve outcomes in patients having surgical ablation and concomitant cardiac surgery. This review summarizes the technology behind alternative energy sources used to treat AF. Alternative energy sources include hypothermic sources (cryoablation) and hyperthermic sources (radiofrequency, microwave, laser, ultrasound). For each source, the biophysical background, mode of tissue injury, factors affecting lesion size, and advantages and complications are discussed.