Adoption and clinical outcomes of fenestrated endovascular aneurysm repair in a regional, multistate community hospital system.

OBJECTIVE: Complex endovascular abdominal aortic aneurysm (AAA) repair techniques have evolved over the last decade, yet patterns of physician and hospital system adoption of fenestrated endovascular aneurysm repair (FEVAR) remain poorly defined. We investigated clinical outcomes, use trends, and surgeon and hospital experience for FEVAR in a large community hospital system. METHODS: We conducted a retrospective cohort study of all FEVAR procedures within our 5-state hospital system between April 2012 and June 2021. AAA repair volumes (open, EVAR, and FEVAR) were captured at the hospital and surgeon levels using Current Procedural Terminology and International Classification of Diseases codes. Clinical and outcomes data were collected for FEVAR patients. To consider if surgeon or hospital experience influenced outcomes, sequential case number was used to divide patients into surgeon experience and hospital experience groups. Inverse probability weighted and generalized linear mixed models, adjusted for demographics and comorbidities, were built to examine risk-adjusted outcomes for surgeon and hospital experience groups. RESULTS: Of 3850 patients treated with AAA procedures of any kind between 2012 and 2021, 160 (4.2%) underwent FEVAR. FEVAR procedures were performed by 34 different surgeons at 12 hospitals, with intraoperative complications and unplanned adjunctive procedures occurring in 18.8% (n = 30) and 19.4% (n = 31) of patients, respectively. Among FEVAR patients, in-hospital mortality was 1.3% (n = 2) and postoperative morbidity was 16.9% (n = 27). Renal function decline occurred postoperatively in 5.1% of patients. Early (<30 day) postoperative endoleaks occurred in 15.3% of patients (n = 21). Target vessel patency was 95.6% on initial postoperative imaging. Surgeon and hospital experience had a small positive impact on outcomes after the first one to three cases. Significant decreases in operative time, fluoroscopy time, and estimated blood loss were observed with increased surgeon experience, relative to a surgeon's first case (P < .05). There were lower odds of intraoperative complications after a surgeon's first case (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03-0.77, for cases 2-3) or after a hospital's first one to three cases (OR, 0.19; 95% CI, 0.04-0.89, for cases 4-8; OR, 0.12; 95% CI, 0.03-0.55 for cases 9-49). CONCLUSIONS: Clinical outcomes of FEVAR across our hospital system compare favorably with previously published reports. Although system-wide FEVAR adoption increased 3-fold over the last decade, FEVAR continued to be performed by a minority of hospitals in our system. The results from this cohort demonstrate low rates of adverse events, high rates of technical efficiency, and a small impact of surgeon and hospital experience, thereby supporting this advanced endovascular technology as a safe, efficacious, and generalizable treatment alternative to open repair for patients with complex aortic anatomy.

Genetic deletion of Polo-like kinase 2 reduces alpha-synuclein serine-129 phosphorylation in presynaptic terminals but not Lewy bodies.

Phosphorylation of alpha-synuclein at serine-129 is an important marker of pathologically relevant, aggregated forms of the protein in several important human diseases, including Parkinson's disease, Dementia with Lewy bodies, and Multiple system atrophy. Although several kinases have been shown to be capable of phosphorylating alpha-synuclein in various model systems, the identity of the kinase that phosphorylates alpha-synuclein in the Lewy body remains unknown. One member of the Polo-like kinase family, PLK2, is a strong candidate for being the Lewy body kinase. To examine this possibility, we have used a combination of approaches, including biochemical, immunohistochemical, and in vivo multiphoton imaging techniques to study the consequences of PLK2 genetic deletion on alpha-synuclein phosphorylation in both the presynaptic terminal and preformed fibril-induced Lewy body pathology in mouse cortex. We find that PLK2 deletion reduces presynaptic terminal alpha-synuclein serine-129 phosphorylation, but has no effect on Lewy body phosphorylation levels. Serine-129 mutation to the phosphomimetic alanine or the unphosphorylatable analog aspartate does not change the rate of cell death of Lewy inclusion-bearing neurons in our in vivo multiphoton imaging paradigm, but PLK2 deletion does slow the rate of neuronal death. Our data indicate that inhibition of PLK2 represents a promising avenue for developing new therapeutics, but that the mechanism of neuroprotection by PLK2 inhibition is not likely due to reducing alpha-synuclein serine-129 phosphorylation and that the true Lewy body kinase still awaits discovery.

Cardiovascular procedural deferral and outcomes over COVID-19 pandemic phases: A multi-center study.

BACKGROUND: The COVID-19 pandemic has disrupted routine cardiovascular care, with unclear impact on procedural deferrals and associated outcomes across diverse patient populations. METHODS: Cardiovascular procedures performed at 30 hospitals across 6 Western states in 2 large, non-profit healthcare systems (Providence St. Joseph Health and Stanford Healthcare) from December 2018-June 2020 were analyzed for changes over time. Risk-adjusted in-hospital mortality was compared across pandemic phases with multivariate logistic regression. RESULTS: Among 36,125 procedures (69% percutaneous coronary intervention, 13% coronary artery bypass graft surgery, 10% transcatheter aortic valve replacement, and 8% surgical aortic valve replacement), weekly volumes changed in 2 distinct phases after the initial inflection point on February 23, 2020: an initial period of significant deferral (COVID I: March 15-April 11) followed by recovery (COVID II: April 12 onwards). Compared to pre-COVID, COVID I patients were less likely to be female (P = .0003), older (P < .0001), Asian or Black (P = .02), or Medicare insured (P < .0001), and COVID I procedures were higher acuity (P < .0001), but not higher complexity. In COVID II, there was a trend toward more procedural deferral in regions with a higher COVID-19 burden (P = .05). Compared to pre-COVID, there were no differences in risk-adjusted in-hospital mortality during both COVID phases. CONCLUSIONS: Significant decreases in cardiovascular procedural volumes occurred early in the COVID-19 pandemic, with disproportionate impacts by race, gender, and age. These findings should inform our approach to future healthcare disruptions.

Trends in vascular complications and associated treatment strategies following transfemoral transcatheter aortic valve replacement.

OBJECTIVE: Vascular complications (VC) and bleeding complications impact morbidity and mortality after transfemoral transcatheter aortic valve replacement (TF-TAVR). Few contemporary studies have detailed these complications, associated treatment strategies, or clinical outcomes. We examined the incidence, predictors, treatment strategies, and outcomes of VCs in a multicenter cohort of patients undergoing TF-TAVR. METHODS: We performed a retrospective registry and chart review of all nonclinical trial TF-TAVR patients from seven centers within a five-state hospital system from 2012 to 2016. Bleeding and VC were recorded as defined by the Valve Academic Research Consortium recommendations. Procedural and 30-day outcomes and 1-year mortality were compared between patients with no, minor, or major VC. Multivariable logistic and Cox regressions were used to identify predictors of major VC and mortality, respectively. RESULTS: Over the study period, 1573 patients underwent TF-TAVR, with 96 (6.1%) experiencing a major VC and 77 (4.9%) experiencing a minor VC. The majority of VCs were access site related (74.2%), occurred intraoperatively (52.6%), and required interventional treatment (73.2%). The site, timing, and treatment method of VCs did not significantly change over the study period. Patients with VCs had a greater need for blood transfusion, longer postoperative length of stay, higher rates of cardiac events, increased vascular-related 30-day readmission, and higher 30-day mortality. Female sex (odds ratio [OR], 3.00; 95% CI, 1.91-4.72) and prior percutaneous coronary intervention (OR, 2.14 ; 95% CI, 1.38-3.31) were the strongest predictors of major VC. VCs modestly decreased over the study period: every 90-day increase in surgery date decreased the odds of major VC by 6% (95% CI, 1%-10%). Patients with major VCs had worse 1-year survival (OR, 79%; 95% CI, 69%-86%) compared with patients with minor VCs (OR, 92%; 95% CI, 82%-96%) or no VCs (OR, 88%; 95% CI, 87%-90%; P = .002). However, for patients who survived more than 30 days, the 1-year survival did not differ between groups For patients who survived more than 30 days, male sex (hazard ratio, 1.84; 95% CI, 1.30-2.60) and the logit of STS mortality risk score (hazard ratio, 1.98; 95% CI, 1.48-2.65) were the strongest predictors of mortality. After adjusting for other factors, minor and major VC were not predictors of 1-year mortality for patients who survived more than 30 days. CONCLUSIONS: In our contemporary cohort, VCs after TF-TAVR have modestly decreased in recent years, but continue to impact perioperative outcomes. Patient selection, consideration of alternative access routes, and prompt recognition and treatment of VCs are critical elements in optimizing early clinical outcomes after TF-TAVR.

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.

Quality of life among injectable and oral disease-modifying therapy users in the Pacific Northwest Multiple Sclerosis Registry.

BACKGROUND: Nine oral disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS) in the United States. Few studies have examined self-reported quality of life (QoL) and functional status outcomes among patients who switch to oral medications from injectable MS therapies. This study compares self-reported QoL and disability status between participants switching from injectable to oral DMTs, to those who stay on injectable DMTs continuously for the same time period. METHODS: Longitudinal data were assessed from relapsing MS participants in the Pacific Northwest MS Registry completing a minimum of two surveys between 2012 and 2018 with a maximum of 36 months between surveys. Stayers were defined as those who remained on injectable DMTs continuously from Time 1 to Time 2; switchers were those who switched from injectable to either fingolimod, teriflunomide or dimethyl fumarate during the same time interval. Outcomes of interest were physical and psychological QoL, measured by the Multiple Sclerosis Impact Scale (MSIS-29), and disability, measured by the Patient Determined Disease Steps (PDDS). To analyze the effect of switching to oral DMT on outcomes at Time 2, a one-to-two propensity score matching (PSM) was used to match switchers to stayers. Outcomes at Time 2 were analyzed using paired t-test for QoL scores, and Stuart Maxwell test for PDDS as a categorical variable. RESULTS: Among 2385 participants who returned consecutive yearly surveys, 413 met the inclusion criteria for stayers and 66 for switchers. After one-to-two PSM, 124 stayers were matched to 62 switchers. Paired t-test showed no differences between switchers and stayers for physical (mean difference: - 0.41; [95% confidence interval CI: - 3.3-2.4]; p = 0.78) or psychological (mean difference: - 0.23; [95% CI, - 1.6- 1.1]; p = 0.74) QoL. Additionally, no differences were seen between switchers and stayers in self-reported disability status. CONCLUSIONS: MS registry participants who switched to an oral DMT from injectable showed no significant differences in QoL or self-reported disability status compared to those remaining on injectable DMT continuously in the same time period.

Monosomy 17 in potentially curable HER2-amplified breast cancer: prognostic and predictive impact.

PURPOSE: HER2 copy number by fluorescence in situ hybridization (FISH) is typically reported relative to the centromere enumeration probe 17 (CEP17). HER2/CEP17 ratio could be impacted by alterations in the number of chromosome 17 copies. Monosomy of chromosome 17 (m17) is found in ~ 1900 cases of early-stage HER2-positive breast cancer annually in the United States; however, the efficacy of HER2-directed trastuzumab therapy in these patients is not well characterized. Here, we retrospectively identified HER2-amplified, stage I-III breast cancers with m17 and characterized the impact of trastuzumab treatment. METHODS: From January 1, 2000 to June 1, 2011, we identified 99 women with HER2-amplified m17 breast cancers, as defined by a CEP17 signal of < 1.5 per nucleus and a HER2/CEP17 ratio of ≥ 2.0. RESULTS: Most HER2-amplified m17 patients were treated with trastuzumab plus chemotherapy (51%, n = 50), whereas 31% (n = 31) received chemotherapy alone and 18% (n = 18) received no chemotherapy. The 4-year overall survival (OS) was superior with trastuzumab compared to chemotherapy alone or no chemotherapy (100 vs. 93 vs. 81%, respectively; p = 0.005). OS was not influenced by estrogen/progesterone-receptor (ER/PR) status, tumor stage, or degree of FISH positivity. A proportion of patients who would be considered HER2-negative by standard immunohistochemistry staging criteria (0-1+) were HER2 amplified by FISH. CONCLUSIONS: In the largest series reported to date, patients with HER2-amplified m17 cancers treated with trastuzumab have outcomes comparable to patients from the large phase III adjuvant trastuzumab trials who were HER2-positive, supporting the critical role of HER2-directed therapy in this patient population.

Three-year clinical outcomes of relapsing multiple sclerosis patients treated with dimethyl fumarate in a United States community health center.

BACKGROUND: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. OBJECTIVE: To track DMF patients' tolerability, disease progression, and lymphopenia. METHODS: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review. RESULTS: The mean age of patients starting DMF was 49.4 ± 12.0 years and 70% transitioned from a previous disease-modifying therapy (DMT). Of the patients, 38% discontinued DMF, 76% of whom discontinued due to side effects. Clinical relapse and MRI activity were low. Comparing patients who transitioned from interferon-ß (IFN), glatiramer acetate (GA), or natalizumab (NTZ), patients previously on NTZ had higher rates of relapse than those previously on GA (annualized relapse rate p = 0.039, percent relapse p = 0.021). Grade III lymphopenia developed in 11% of patients. Lymphopenia was associated with older age ( p < 0.001) and longer disease duration ( p < 0.001). CONCLUSION: Given the high rates of lymphopenia and discontinuation, it has become our clinical practice to more closely scrutinize older patients and those with a longer disease duration who are potential candidates for initiating DMF therapy.

A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links in Hair Bundles.

Tip links are thought to gate the mechanically sensitive transduction channels of hair cells, but how they form during development and regeneration remains mysterious. In particular, it is unclear how tip links are strung between stereocilia so that they are oriented parallel to a single axis; why their polarity is uniform despite their constituent molecules' intrinsic asymmetry; and why only a single tip link is present at each tip-link position. We present here a series of simple rules that reasonably explain why these phenomena occur. In particular, our model relies on each of the two ends of the tip link having distinct Ca2+-dependent stability and being connected to different motor complexes. A simulation employing these rules allowed us to explore the parameter space for the model, demonstrating the importance of the feedback between transduction channels and angled links, links that are 60° off-axis with respect to mature tip links. We tested this key aspect of the model by examining angled links in chick cochlea hair cells. As implied by the assumptions used to generate the model, we found that angled links were stabilized if there was no tip link at the tip of the upper stereocilium, and appeared when transduction channels were blocked. The model thus plausibly explains how tip-link formation and pruning can occur.

Telehealth Stroke Dysphagia Evaluation Is Safe and Effective.

BACKGROUND: Rapid evaluation of dysphagia poststroke significantly lowers rates of aspiration pneumonia. Logistical barriers often significantly delay in-person dysphagia evaluation by speech language pathologists (SLPs) in remote and rural hospitals. Clinical swallow evaluations delivered via telehealth have been validated in a number of clinical contexts, yet no one has specifically validated a teleswallow evaluation for in-hospital post-stroke dysphagia assessment. METHODS: A team of 6 SLPs experienced in stroke care and a telestroke neurologist designed, implemented, and tested a teleswallow evaluation for acute stroke patients, in which 100 patients across 2 affiliated, urban certified stroke centers were sequentially evaluated by a bedside and telehealth SLP. Inter-rater reliability was analyzed using percent agreement, Cohen's kappa, Kendall's tau-b, and Wilcoxon matched-pairs signed rank tests. Logistic regression models accounting for age and gender were used to test the impact of stroke severity and stroke location on agreement. RESULTS: We found excellent agreement for both liquid (91% agreement; kappa = 0.808; Kendall's tau-b = 0.813, p < 0.001; Wilcoxon signed rank = -0.818, p = 0.417) and solid (87% agreement; kappa = 0.792; Kendall's tau-b = 0.844, p < 0.001; Wilcoxon signed rank = 0.243, p = 0.808) dietary textures. From regression modeling, there is suggestive but inconclusive evidence that higher National Institute of Health Stroke Scale (NIHSS) scores correlate with lower levels of agreement for liquid diet recommendations (OR [95% CI] 0.895 [0.793-1.01]; p = 0.07). There was no impact of NIHSS score for solid diet recommendations and no impact of stroke location on solid or liquid diet recommendations. Qualitatively, we identified professional, logistical, technical, and patient barriers to implementation, many of which resolved with experience over time. CONCLUSIONS: Dysphagia evaluation by a remote SLP via telehealth is safe and effective following stroke. We plan to implement teleswallow across our multistate telestroke network as standard practice for poststroke dysphagia evaluation.

Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.

Sound detection by inner ear hair cells requires tip links that interconnect mechanosensory stereocilia and convey force to yet unidentified transduction channels. Current models postulate a static composition of the tip link, with protocadherin 15 (PCDH15) at the lower and cadherin 23 (CDH23) at the upper end of the link. In terminally differentiated mammalian auditory hair cells, tip links are subjected to sound-induced forces throughout an organism's life. Although hair cells can regenerate disrupted tip links and restore hearing, the molecular details of this process are unknown. We developed a novel implementation of backscatter electron scanning microscopy to visualize simultaneously immuno-gold particles and stereocilia links, both of only a few nanometers in diameter. We show that functional, mechanotransduction-mediating tip links have at least two molecular compositions, containing either PCDH15/CDH23 or PCDH15/PCDH15. During regeneration, shorter tip links containing nearly equal amounts of PCDH15 at both ends appear first. Whole-cell patch-clamp recordings demonstrate that these transient PCDH15/PCDH15 links mediate mechanotransduction currents of normal amplitude but abnormal Ca(2+)-dependent decay (adaptation). The mature PCDH15/CDH23 tip link composition is re-established later, concomitant with complete recovery of adaptation. Thus, our findings provide a molecular mechanism for regeneration and maintenance of mechanosensory function in postmitotic auditory hair cells and could help identify elusive components of the mechanotransduction machinery.

Correlation of actin crosslinker and capper expression levels with stereocilia growth phases.

During development of the chick cochlea, actin crosslinkers and barbed-end cappers presumably influence growth and remodeling of the actin paracrystal of hair cell stereocilia. We used mass spectrometry to identify and quantify major actin-associated proteins of the cochlear sensory epithelium from E14 to E21, when stereocilia widen and lengthen. Tight actin crosslinkers (i.e. fascins, plastins, and espin) are expressed dynamically during cochlear epithelium development between E7 and E21, with FSCN2 replacing FSCN1 and plastins remaining low in abundance. Capping protein, a barbed-end actin capper, is located at stereocilia tips; it is abundant during growth phase II, when stereocilia have ceased elongating and are increasing in diameter. Capping protein levels then decline during growth phase III, when stereocilia reinitiate barbed-end elongation. Although actin crosslinkers are readily detected by electron microscopy in developing chick cochlea stereocilia, quantitative mass spectrometry of stereocilia isolated from E21 chick cochlea indicated that tight crosslinkers are present there in stoichiometric ratios relative to actin that are much lower than their ratios for vestibular stereocilia. These results demonstrate the value of quantitation of global protein expression in chick cochlea during stereocilia development.

Presynaptic alpha-synuclein aggregation in a mouse model of Parkinson's disease.

Parkinson's disease and dementia with Lewy bodies are associated with abnormal neuronal aggregation of α-synuclein. However, the mechanisms of aggregation and their relationship to disease are poorly understood. We developed an in vivo multiphoton imaging paradigm to study α-synuclein aggregation in mouse cortex with subcellular resolution. We used a green fluorescent protein-tagged human α-synuclein mouse line that has moderate overexpression levels mimicking human disease. Fluorescence recovery after photobleaching (FRAP) of labeled protein demonstrated that somatic α-synuclein existed primarily in an unbound, soluble pool. In contrast, α-synuclein in presynaptic terminals was in at least three different pools: (1) as unbound, soluble protein; (2) bound to presynaptic vesicles; and (3) as microaggregates. Serial imaging of microaggregates over 1 week demonstrated a heterogeneous population with differing α-synuclein exchange rates. The microaggregate species were resistant to proteinase K, phosphorylated at serine-129, oxidized, and associated with a decrease in the presynaptic vesicle protein synapsin and glutamate immunogold labeling. Multiphoton FRAP provided the specific binding constants for α-synuclein's binding to synaptic vesicles and its effective diffusion coefficient in the soma and axon, setting the stage for future studies targeting synuclein modifications and their effects. Our in vivo results suggest that, under moderate overexpression conditions, α-synuclein aggregates are selectively found in presynaptic terminals.

Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity.

Measuring the abundance of many proteins over a broad dynamic range requires accurate quantitation. We show empirically that, in MS experiments, relative quantitation using summed dissociation-product ion-current intensities is accurate, albeit variable from protein to protein, and outperforms spectral counting. By applying intensities to quantify proteins in two complex but related tissues, chick auditory and vestibular sensory epithelia, we find that glycolytic enzymes are enriched threefold in auditory epithelia, whereas enzymes responsible for oxidative phosphorylation are increased at least fourfold in vestibular epithelia. This striking difference in relative use of the two ATP-production pathways likely reflects the isolation of the auditory epithelium from its blood supply, necessary to prevent heartbeat-induced mechanical disruptions. The global view of protein expression afforded by label-free quantitation with a wide dynamic range reveals molecular specialization at a tissue or cellular level.

Impella as a bridge-to-closure in post-infarction ventricular septal defect: a case series.

Background: Post-infarction ventricular septal defect (PIVSD) is a rare, life-threatening complication of acute myocardial infarction (AMI). Few studies report the use of mechanical circulatory support (MCS) for the treatment of cardiogenic shock in this setting. We describe our experience using a microaxial, transvalvular device (Impella, Abiomed, Danvers, MA, USA) as a bridge-to-closure for PIVSD. Case summary: We identified 13 patients from two centres with cardiogenic shock due to PIVSD who received an Impella device between January 2016 and February 2022. Nine patients were transferred from another hospital, three with MCS devices [two intra-aortic balloon pumps (IABP), 1 Impella CP]. Eight patients received Impella 5.0, three received Impella 5.5 (one escalated from Impella CP), and two received Impella CP. The median time from AMI to Impella insertion was 5 (3-6) days. Five patients died on Impella support without an attempt to close the ventricular septum (VSD). Seven patients underwent successful VSD closure: six had surgical and one had percutaneous closure. One patient died during attempted percutaneous closure. Time from Impella insertion to VSD closure was 10.5 (7.8-14.0) days. Time from AMI to Impella was 5.0 (2.0-5.3) days in the group that survived to closure, and 6.0 (4.0-7.0) days in those who did not. Thirty-day mortality was 46%. Discussion: Support with Impella improved clinical stability in most patients, yet multi-system organ failure leading to death occurred in many patients. Patients who survived closure had earlier time from AMI to Impella, underscoring that prompt recognition of PIVSD and initiation of MCS may improve survival to surgical or percutaneous closure.

Transcatheter Aortic Valve Replacement Outcomes in End-Stage Renal Disease Patients on Hemodialysis Requiring Midodrine.

Background: Patients with dialysis-dependent end-stage renal disease (ESRD) taking midodrine may be at high risk for poor outcomes following transcatheter aortic valve replacement (TAVR). We evaluated dialysis-dependent ESRD patients taking midodrine. Methods: We conducted a retrospective analysis of non-clinical trial TAVR patients from February 2012 to December 2020 from 11 facilities in a Western US health system. Patient groups included ESRD patients on midodrine before TAVR (ESRD [+M]), ESRD patients without midodrine (ESRD [-M]), and non-ESRD patients. The endpoints of 30-day and 1-year mortality were represented by Kaplan-Meier survival estimator and compared by log-rank test. Results: Forty-five ESRD (+M), 216 ESRD (-M), and 6898 non-ESRD patients were included. ESRD patients had more comorbid conditions, despite no significant difference in predicted Society of Thoracic Surgeons mortality risk between ESRD (+M) and ESRD (-M) (8.7% vs. 9.2%, p = 0.491). Thirty-day mortality was significantly higher for ESRD (+M) patients vs. ESRD (-M) patients (20.1% vs. 5.6%, p = 0.001) and for ESRD (+M) vs. non-ESRD patients (2.5%, p < 0.001). One-year mortality trended higher for ESRD (+M) vs. ESRD (-M) patients (41.9% vs. 29.8%, p = 0.07), and was significantly higher for ESRD (+M) vs. non-ESRD patients (10.7%, p < 0.001). Compared to ESRD (-M), ESRD (+M) patients had a higher incidence of 30-day stroke (6.7% vs. 1.4%, p = 0.033), 30-day vascular complications (6.7% vs. 0.9%, p = 0.011), and a lower rate of discharge to home (62.2% vs. 84.7%, p < 0.001). In contrast, ESRD (-M) patients had no significant differences from non-ESRD patients for these outcomes. Conclusions: Our experience suggests ESRD patients on midodrine are a higher acuity population with worse survival after TAVR, compared to ESRD patients not on midodrine. These findings may help with risk stratification for ESRD patients undergoing TAVR.

Axillary transvalvular microaxial pump as extended bridge to transcatheter aortic valve replacement in cardiogenic shock with severe aortic stenosis.

Cardiogenic shock in the setting of severe aortic stenosis is associated with poor outcomes. We describe 5 patients with cardiogenic shock and severe aortic stenosis who received an axillary microaxial pump (Impella) as an extended bridge to transcatheter aortic valve replacement. The median (range) age was 65 (61-87) years old, 80% were male, and 80% presented with stage D or E cardiogenic shock. In most cases, balloon aortic valvuloplasty was performed prior to pump insertion. Stabilization by Impella allowed for heart team evaluation and additional interventions, including percutaneous coronary intervention, MitraClip, and cardioversion. After a median (range) of 7 (5-14) days of Impella support, semi-elective transcatheter aortic valve replacement was successfully performed. All patients survived to discharge. Four patients (80%) were alive beyond 1 year. In these high-risk patients, prolonged support with a microaxial pump allowed for stabilization, ancillary interventions, and multi-disciplinary heart team evaluation prior to transcatheter aortic valve replacement.

Comparable Outcomes for Transcarotid and Transfemoral Transcatheter Aortic Valve Replacement at a High Volume US Center.

With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods: We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center.

Discordance Between Standard Equations for Determination of LDL Cholesterol in Patients With Atherosclerosis.

BACKGROUND: Accurate estimation of low-density lipoprotein cholesterol (LDL-C) is important for guiding cholesterol-lowering therapy. Different methods currently exist to estimate LDL-C. OBJECTIVES: This study sought to assess discordance of estimated LDL-C using the Friedewald, Sampson, and Martin/Hopkins equations. METHODS: Electronic health record data from patients with atherosclerotic cardiovascular disease and triglyceride (TG) levels of <400 mg/dL between October 1, 2015, and June 30, 2019, were retrospectively analyzed. LDL-C was estimated using the Friedewald, Sampson, and Martin/Hopkins equations. Patients were categorized as concordant if LDL-C was <70 mg/dL with each pairwise comparison of equations and as discordant if LDL-C was <70 mg/dL for the index equation and ≥70 mg/dL for the comparator. RESULTS: The study included 146,106 patients with atherosclerotic cardiovascular disease (mean age: 68 years; 56% male; 91% White). The Martin/Hopkins equation consistently estimated higher LDL-C values than the Friedewald and Sampson equations. Discordance rates were 15% for the Friedewald vs Martin/Hopkins comparison, 9% for the Friedewald vs Sampson comparison, and 7% for the Sampson vs Martin/Hopkins comparison. Discordance increased at lower LDL-C cutpoints and in those with elevated TG levels. Among patients with TG levels of ≥150 mg/dL, a >10 mg/dL difference in LDL-C was present in 67%, 27%, and 23% of patients when comparing the Friedewald vs Martin/Hopkins, Friedewald vs Sampson, and Sampson vs Martin/Hopkins equations, respectively. CONCLUSIONS: Clinically meaningful differences in estimated LDL-C exist among equations, particularly at TG levels of ≥150 mg/dL and/or lower LDL-C levels. Reliance on the Friedewald and Sampson equations may result in the underestimation and undertreatment of LDL-C in those at increased risk.

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.