A Case of Transcatheter Aortic Valve Implantation in a Centenarian Patient.

Calcified aortic stenosis has become the most common form of acquired valvular heart disease in very old patients. Despite this fact, a majority of these patients were turned down by surgery owing to a risk of mortality > 10% in patients older than 90 years. In recent years, transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic option for severe aortic stenosis. However, there is a paucity of data regarding the outcomes of TAVI in patients older than 100 years. We present the oldest patient who has undergone successful TAVI reported in the current literature.

Evaluation of anticoagulation use and subsequent stroke in patients with atrial fibrillation after empiric surgical left atrial appendage closure: A retrospective case-control study.

BACKGROUND: Surgical exclusion of the left atrial appendage (LAA) can be performed at the time of cardiac operation as a potential modality to decrease cardioembolic risk attributable to atrial fibrillation (AF), but it remains unclear if this decreases stroke incidence. Furthermore, it is not known whether LAA exclusion impacts the decision to discontinue anticoagulation impacting subsequent stroke risk. HYPOTHESIS: LAA exclusion does not significantly alter subsequent anticoagulation use or stroke incidence. METHODS: We studied 124 patients from Olmsted County with prior history of AF who underwent cardiac surgery at our institution between 1993 and 2015. Patients were divided into two groups on the basis of LAA exclusion and matched (1:1) according to 16 pretreatment variables using propensity scores obtained from a logistic regression model. Outcome data collected through chart review for survival, stroke, and the presence and duration of anticoagulation were compared between groups. RESULTS: The proportion of patients receiving anticoagulation at discharge and at 5 years was not significantly different between patients who underwent LAA exclusion and those who did not; 90% vs 81%, P = 0.156, 48% vs 49%, P = 0.722, respectively. On Kaplan-Meier analysis there were no significant differences in time free from stroke between cases and controls. Patients discharged on oral anticoagulation (OAC) had significantly lower risk of stroke (HR = 0.19, 95% confidence interval [CI] = 0.06-0.59, P = 0.004), independent of whether LAA closure was used. CONCLUSION: LAA exclusion did not appear to reduce early or late stroke. Only OAC was associated with a reduction in stroke risk, underscoring the need for continued anticoagulation in high-risk patients.

Association of Surgical Left Atrial Appendage Occlusion With Subsequent Stroke and Mortality Among Patients Undergoing Cardiac Surgery.

Importance: Surgical occlusion of the left atrial appendage (LAAO) may be performed during concurrent cardiac surgery. However, few data exist on the association of LAAO with long-term risk of stroke, and some evidence suggests that this procedure may be associated with subsequent development of atrial fibrillation (AF). Objective: To evaluate the association of surgical LAAO performed during cardiac surgery with risk of stroke, mortality, and development of subsequent AF. Design, Setting, and Participants: Retrospective cohort study using a large US administrative database that contains data from adult patients (≥18 years) with private insurance or Medicare Advantage who underwent coronary artery bypass graft (CABG) or valve surgery between January 1, 2009, and March 30, 2017, with final follow-up on March 31, 2017. One-to-one propensity score matching was used to balance patients on 76 dimensions to compare those with vs without LAAO, stratified by history of prior AF at the time of surgery. Exposures: Surgical LAAO vs no surgical LAAO during cardiac surgery. Main Outcomes and Measures: The primary outcomes were stroke (ie, ischemic stroke or systemic embolism) and all-cause mortality. The secondary outcomes were postoperative AF (AF within 30 days after surgery among patients without prior AF) and long-term AF-related health utilization (event rates of outpatient visits and hospitalizations). Results: Among 75 782 patients who underwent cardiac surgery (mean age, 66.0 [SD, 11.2] years; 2 2091 [29.2%] women, 25 721 [33.9%] with preexisting AF), 4374 (5.8%) underwent concurrent LAAO, and mean follow-up was 2.1 (SD, 1.9) years. In the 8590 propensity score-matched patients, LAAO was associated with a reduced risk of stroke (1.14 vs 1.59 events per 100 person-years; hazard ratio [HR], 0.73 [95% CI, 0.56-0.96]; P = .03) and mortality (3.01 vs 4.30 events per 100 person-years; HR, 0.71 [95% CI, 0.60-0.84]; P < .001). LAAO was associated with higher rates of AF-related outpatient visits (11.96 vs 10.26 events per person-year; absolute difference, 1.70 [95% CI, 1.60-1.80] events per person-year; rate ratio, 1.17 [95% CI, 1.10-1.24]; P < .001) and hospitalizations (0.36 vs 0.32 event per person-year; absolute difference, 0.04 [95% CI, 0.02-0.06] event per person-year; rate ratio, 1.13 [95% CI, 1.05-1.21]; P = .002). In patients with prior AF (6438/8590 [74.9%]) with vs without LAAO, risk of stroke was 1.11 vs 1.71 events per 100 person-years (HR, 0.68 [95% CI, 0.50-0.92]; P = .01) and risk of mortality was 3.22 vs 4.93 events per 100 person-years (HR, 0.67 [95% CI, 0.56-0.80]; P < .001), respectively. In patients without prior AF (2152/8590 [25.1%]) with vs without LAAO, risk of stroke was 1.23 vs 1.26 events per 100 person-years (HR, 0.95 [95% CI, 0.54-1.68]), risk of mortality was 2.30 vs 2.49 events per 100 person-years (HR, 0.92 [95% CI, 0.61-1.37]), and risk of postoperative AF was 27.7% vs 20.2% events per 100 person-years (HR, 1.46 [95% CI, 1.22-1.73]; P < .001). The interaction term between prior AF and LAAO was not significant (P = .29 for stroke and P = .16 for mortality). Conclusions and Relevance: Among patients undergoing cardiac surgery, concurrent surgical LAAO, compared with no surgical LAAO, was associated with reduced risk of subsequent stroke and all-cause mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of surgical LAAO.

Myosin MyTH4-FERM structures highlight important principles of convergent evolution.

Myosins containing MyTH4-FERM (myosin tail homology 4-band 4.1, ezrin, radixin, moesin, or MF) domains in their tails are found in a wide range of phylogenetically divergent organisms, such as humans and the social amoeba Dictyostelium (Dd). Interestingly, evolutionarily distant MF myosins have similar roles in the extension of actin-filled membrane protrusions such as filopodia and bind to microtubules (MT), suggesting that the core functions of these MF myosins have been highly conserved over evolution. The structures of two DdMyo7 signature MF domains have been determined and comparison with mammalian MF structures reveals that characteristic features of MF domains are conserved. However, across millions of years of evolution conserved class-specific insertions are seen to alter the surfaces and the orientation of subdomains with respect to each other, likely resulting in new sites for binding partners. The MyTH4 domains of Myo10 and DdMyo7 bind to MT with micromolar affinity but, surprisingly, their MT binding sites are on opposite surfaces of the MyTH4 domain. The structural analysis in combination with comparison of diverse MF myosin sequences provides evidence that myosin tail domain features can be maintained without strict conservation of motifs. The results illustrate how tuning of existing features can give rise to new structures while preserving the general properties necessary for myosin tails. Thus, tinkering with the MF domain enables it to serve as a multifunctional platform for cooperative recruitment of various partners, allowing common properties such as autoinhibition of the motor and microtubule binding to arise through convergent evolution.

Direct real-time detection of the structural and biochemical events in the myosin power stroke.

A principal goal of molecular biophysics is to show how protein structural transitions explain physiology. We have developed a strategic tool, transient time-resolved FRET [(TR)(2)FRET], for this purpose and use it here to measure directly, with millisecond resolution, the structural and biochemical kinetics of muscle myosin and to determine directly how myosin's power stroke is coupled to the thermodynamic drive for force generation, actin-activated phosphate release, and the weak-to-strong actin-binding transition. We find that actin initiates the power stroke before phosphate dissociation and not after, as many models propose. This result supports a model for muscle contraction in which power output and efficiency are tuned by the distribution of myosin structural states. This technology should have wide application to other systems in which questions about the temporal coupling of allosteric structural and biochemical transitions remain unanswered.

Characterization of a myosin VII MyTH/FERM domain.

A group of closely related myosins is characterized by the presence of at least one MyTH/FERM (myosin tail homology; band 4.1, ezrin, radixin, moesin) domain in their C-terminal tails. This domain interacts with a variety of binding partners, and mutations in either the MyTH4 or the FERM domain of myosin VII and myosin XV result in deafness, highlighting the functional importance of each domain. The N-terminal MyTH/FERM region of Dictyostelium myosin VII (M7) has been isolated as a first step toward gaining insight into the function of this domain and its interaction with binding partners. The M7 MyTH4/FERM domain (MF1) binds to both actin and microtubules in vitro, with dissociation constants of 13.7 and 1.7 µM, respectively. Gel filtration and UV spectroscopy reveal that MF1 exists as a monomer in solution and forms a well-folded, compact conformation with a high degree of secondary structure. These results indicate that MF1 forms an integrated structural domain that serves to couple actin filaments and microtubules in specific regions of the cytoskeleton.