Mortality Associated With Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: North American Mitraclip for Functional Mitral Regurgitation Registry.

The association, if any, between the effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients who undergo mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip system (Abbott Vascular, Santa Clara, CA). This study's objective was to determine the association between EROA/LVEDV and 1-year mortality in patients who undergo m-TEER with MitraClip. In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. We studied 525 patients with secondary MR who underwent m-TEER. Most patients were male (63%) and were New York Heart Association class III (61%) or IV (21%). Mitral regurgitation was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely, with median = 0.19 mm2/ml, interquartile range [0.12,0.28] mm2/ml, and 187 patients (36%) had values <0.15 mm2/ml. Postprocedural mitral regurgitation severity was substantially alleviated, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%; 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation (Ln) of EROA/LVEDV was associated with 1-year mortality (odds ratio 0.600, 95% confidence interval 0.386 to 0.933, p = 0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. In conclusion, lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in this multicenter registry. The slope of the association is steep at low values but gradually flattens as Ln(EROA/LVEDV) increases.

Projected Outcomes of Optimized Statin and Ezetimibe Therapy in US Military Veterans with Coronary Artery Disease.

Importance: Many patients with coronary artery disease (CAD) do not achieve the guideline-directed goals for low-density lipoprotein cholesterol (LDL-C) levels. Objective: To estimate reductions in the rates of adverse events associated with CAD in a large US military veteran population that may be achieved through use of optimized statin therapy alone or with ezetimibe compared with the prevailing lipid-lowering therapy (LLT). Design, Setting, and Participants: In this observational cohort study, US military veterans with CAD were identified by coronary angiography between June 2015 and September 2020 across 82 US Department of Veterans Affairs health care facilities. Exposures: The exposures were observed LLT, LLT with an optimized statin regimen, and LLT with optimized statin and ezetimibe. Main Outcomes and Measures: Observed rates of death, myocardial infarction, stroke, and coronary revascularization, and potential reductions in those outcomes with optimized LLT based on expected further reductions in LDL-C levels and application of formulas from The Cholesterol Treatment Trialists' Collaboration. Results: The analysis cohort comprised 111 954 veterans (mean [SD] age, 68.4 [8.8] years; 109 390 men [97.7%]; 91 589 White patients [81.8%]; 17 592 Black patients [15.7%]). The median (IQR) observation period for this study was 3.4 (2.1-4.0) years. At the time of index angiography, 66 877 patients (59.7%) were treated with statin therapy, and 623 patients (0.6%) were treated with ezetimibe. At 6 months, the number of patients with statin prescriptions increased to 74 400 (68.7%), but the number of patients with high-intensity statin prescriptions was only 57 297 (52.9%). At 6 months, ezetimibe use remained low (n = 1168 [1.1%]), and LDL-C levels were 70 mg/dL or more in 56 405 patients (52.1%). At 4 years, observed incidences of death, myocardial infarction, stroke, and coronary revascularization were 21.6% (95% CI, 21.3%-21.8%), 5.0% (95% CI, 4.9%-5.2%), 2.2% (95% CI, 2.1%-2.3%), and 15.4% (95% CI, 15.2%-15.7%), respectively. With optimized statin treatment, projected absolute reductions in these incidences were 1.3% (95% CI, 0.9%-1.7%), 0.8% (95% CI, 0.7%-1.0%), 0.2% (95% CI, 0.1%-0.3%), and 2.3% (95% CI, 2.0%-2.7%), respectively. With optimized statin and ezetimibe treatment, projected absolute reductions were 1.8% (95% CI, 1.2%-2.4%), 1.1% (95% CI, 0.9%-1.3%), 0.3% (95% CI, 0.2%-0.4%), and 3.1% (95% CI, 2.6%-3.6%), respectively. Conclusions and Relevance: In this cohort study of veterans with CAD, suboptimal LLT was prevalent in the clinical setting. Optimization of statin therapy was projected to produce clinically relevant reductions in the risks of death and cardiovascular events. Despite a lesser lipid-lowering efficacy of ezetimibe, its widespread use on a population level in conjunction with optimized statin therapy may be associated with further meaningful reductions in cardiovascular risk.

Association of Residual Ischemic Disease With Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Anatomical scoring systems have been used to assess completeness of revascularization but are challenging to apply to large real-world datasets. OBJECTIVES: The aim of this study was to assess the prevalence of complete revascularization and its association with longitudinal clinical outcomes in the U.S. Department of Veterans Affairs (VA) health care system using an automatically computed anatomic complexity score. METHODS: Patients undergoing percutaneous coronary intervention (PCI) between October 1, 2007, and September 30, 2020, were identified, and the burden of prerevascularization and postrevascularization ischemic disease was quantified using the VA SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score. The association between residual VA SYNTAX score and long-term major adverse cardiovascular events (MACE; death, myocardial infarction, repeat revascularization, and stroke) was assessed. RESULTS: A total of 57,476 veterans underwent PCI during the study period. After adjustment, the highest tertile of residual VA SYNTAX score was associated with increased hazard of MACE (HR: 2.06; 95% CI: 1.98-2.15) and death (HR: 1.50; 95% CI: 1.41-1.59) at 3 years compared to complete revascularization (residual VA SYNTAX score = 0). Hazard of 1- and 3-year MACE increased as a function of residual disease, regardless of baseline disease severity or initial presentation with acute or chronic coronary syndrome. CONCLUSIONS: Residual ischemic disease was strongly associated with long-term clinical outcomes in a contemporary national cohort of PCI patients. Automatically computed anatomic complexity scores can be used to assess the longitudinal risk for residual ischemic disease after PCI and may be implemented to improve interventional quality.

Impact of Operator Volumes and Experience on Outcomes After Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting and Tracking (CART) Program.

BACKGROUND: Recent analyses of the volume-outcome relationship for percutaneous coronary intervention (PCI) have suggested a less robust association than previously reported. It is unknown if novel factors such as lifetime operator experience influence this relationship. OBJECTIVES: To assess the relationship between annual volumes and outcomes for PCI and determine whether lifetime operator experience modulates the association. METHODS: Annual PCI volumes for facilities and operators within the Veterans Affairs Healthcare System and their relationship with 30-day mortality following PCI were described. The influence of operator lifetime experience on the volume-outcome relationship was assessed. Hierarchical logistic regression was used to adjust for patient and procedural factors. RESULTS: 57,608 PCIs performed from 2013 to 2018 by 382 operators and 63 institutions were analyzed. Operator annualized PCI volume averaged 47.6 (standard deviation [SD] 49.1) and site annualized volume averaged 189.2 (SD 105.2). Median operator experience was 9.0 years (interquartile range [IQR] 4.0-15.0). There was no independent relationship between operator annual volume, institutional volume, or operator lifetime experience with 30-day mortality (p > 0.10). However, the interaction between operator volume and lifetime experience was associated with a marginal decrease in mortality (odds ratio [OR] 0.9998, 95% CI 0.9996-0.9999). CONCLUSIONS: There were no significant associations between facility or operator-level procedural volume and 30-day mortality following PCI in a nationally integrated healthcare system. There was a marginal association between the interaction of operator lifetime experience, operator annual volume, and 30-day mortality that is unlikely to be clinically relevant, though does suggest an opportunity to explore novel factors that may influence the volume-outcome relationship.

Clinical Characteristics and Outcomes Among Patients Undergoing High-Risk Percutaneous Coronary Interventions by Single or Multiple Operators: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Background High-risk percutaneous coronary intervention (HR-PCI) is increasingly common among contemporary patients with coronary artery disease. Experts have advocated for a collaborative 2-operator approach to support intraprocedural decision-making for these complex interventions. The impact of a second operator on patient and procedural outcomes is unknown. Methods and Results Patients who underwent HR-PCI from 2015 to 2018 within the Veterans Affairs Healthcare System were identified. Propensity-matched cohorts were generated to compare the outcomes following HR-PCI performed by a single or multiple (≥2) operators. The primary end point was the 12-month rate of major adverse cardiovascular events. We identified 6672 patients who underwent HR-PCI during the study period; 6211 (93%) were treated by a single operator, and 461 (7%) were treated by multiple operators, with a nonsignificant trend toward increased multioperator procedures over time. A higher proportion of patients treated by multiple operators underwent left main (10% versus 7%, P=0.045) or chronic total occlusion intervention (11% versus 5%, P<0.001). Lead interventionalists participating in multioperator procedures practiced at centers with higher annual HR-PCI volumes (124±71.3 versus 111±69.2; standardized mean difference, 0.197; P<0.001) but otherwise performed a similar number of HR-PCI procedures per year (34.4±35.3 versus 34.7±30.7; standardized mean difference, 0.388; P=0.841) compared with their peers performing single-operator interventions. In a propensity-matched cohort, there was no significant difference in major adverse cardiovascular events (32% versus 30%, P=0.444) between patients who underwent single-operator versus multioperator HR-PCI. Adjusted analyses accounting for site-level variance showed no significant differences in outcomes. Conclusions Patients who underwent multioperator HR-PCI had similar outcomes compared with single-operator procedures. Further studies are needed to determine if the addition of a second operator offers clinical benefits to a subset of HR-PCI patients undergoing left main or chronic total occlusion intervention.

Fulminant Vasculitis Complicated by ST-Elevation Myocardial Infarction and Stroke.

Acute coronary syndrome is a rare complication of vasculitis. We present a case of fulminant medium-vessel vasculitis, most likely PAN, complicated by STEMI and stroke, that was successfully treated with percutaneous revascularization, high-quality stroke care, and immunosuppression. This case highlights the importance of prompt diagnosis and treatment of vasculitis and the recognition of coronary and cerebral ischemia as potentially serious complications.

Impact of the COVID-19 pandemic on cardiac arrest systems of care.

PURPOSE OF REVIEW: The emergence of severe acute respiratory syndrome coronavirus 2 virus, which causes coronavirus disease 2019 (COVID-19), led to the declaration of a global pandemic by the World Health Organization on March 11, 2020. As of February 6, 2021, over 105 million persons have been infected in 223 countries and there have been 2,290,488 deaths. As a result, emergency medical services and hospital systems have undergone unprecedented healthcare delivery reconfigurations. Here, we review the effects of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) epidemiology and systems of care. RECENT FINDINGS: Areas severely affected by the pandemic have reported increased incidence of OHCA, lower rates of successful resuscitation, and increased mortality. COVID-19 has significantly impacted patient outcomes through increased disease severity, decreased access to care, and the reshaping of emergency medical response and hospital-based healthcare systems and policies. The pandemic has negatively influenced attitudes toward resuscitation and challenged providers with novel ethical dilemmas provoked by the scarcity of healthcare resources. SUMMARY: The COVID-19 pandemic has had direct, indirect, psychosocial, and ethical impacts on the cardiac arrest chain of survival.

Comparison of Patients With Nonobstructive Coronary Artery Disease With Versus Without Myocardial Infarction (from the VA Clinical Assessment Reporting and Tracking [CART] Program).

Comparisons of the outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA) and patients with nonobstructive coronary artery disease (CAD) without myocardial infarction (MI) are limited. Here we compare the outcomes of patients with MINOCA and patients with nonobstructive CAD without MI and assess the influence of medical therapy on outcomes in these patients. Veterans who underwent coronary angiography between 2008 to 2017 with nonobstructive CAD were divided into those with or without pre-procedural troponin elevation. Patients with prior revascularization, heart failure, or who presented with cardiogenic shock, STEMI, or unstable angina were excluded. After propensity matching, outcomes were compared between groups. The primary outcome was major adverse cardiovascular events (MACE: mortality, myocardial infarction, and revascularization) within one year: 3,924 patients with nonobstructive CAD and a troponin obtained prior to angiography were identified (n=1,986 with elevated troponin) and restricted to 1,904 patients after propensity-matching. There was a significantly higher risk of MACE among troponin-positive patients compared with those with a negative troponin (HR 2.37; 95% CI, 1.67 to 3.34). Statin (HR 0.32; 95% CI, 0.22 to 0.49) and ACE inhibitor (HR 0.49; 95% CI, 0.32 to 0.75) therapy after angiography was associated with decreased MACE, while P2Y12 inhibitor, calcium-channel and beta-blocker therapy were not associated with outcomes. In conclusion, Veterans with MINOCA are at increased risk for MACE compared with those with nonobstructive CAD and negative troponin at the time of angiography. Specific medications were associated with a reduction in MACE, suggesting an opportunity to explore novel approaches for secondary prevention in this population.

Outcomes of urgent/emergent transcatheter mitral valve repair (MitraClip): A single center experience.

OBJECTIVES: To describe the outcomes of urgent/emergent transcatheter edge-to-edge mitral valve repair (TMVr) and compare the clinical, echocardiographic, and procedural characteristics of survivors and nonsurvivors. BACKGROUND: TMVr is a treatment strategy for select patients with severe primary or secondary mitral regurgitation. However, knowledge regarding outcomes for urgent/emergent TMVr is limited. METHODS: All urgent or emergent TMVr procedures using MitraClip performed at the University of Washington Medical Center between January 2018 and March 2019 were identified and clinical, echocardiographic, hemodynamic, procedural, and outcomes data were obtained by chart review. Outcomes included all-cause mortality, hospital mortality, procedural success, periprocedural complications, and hospital readmission. RESULTS: Of the 20 patients who underwent urgent/emergent TMVr, eight were treated for cardiogenic shock (CS), four for acute decompensated heart failure (ADHF) with hypoxemic respiratory failure requiring mechanical ventilation, and eight for ADHF with failure of inpatient medical therapy. Mechanical circulatory support (MCS) was used in six patients; preceding TMVr in three patients and immediately post-TMVr in three patients. Overall, 30-day mortality and hospital readmission rates were 21 and 13%, respectively. Over a median 153 days (IQR 20-491) of follow-up, 10 patients (50%) died. Preprocedure CS, new or ongoing MCS post-TMVr, refractory respiratory failure post-TMVr, and acute kidney injury post-TMVr were associated with mortality. CONCLUSIONS: In a single-center retrospective analysis, urgent/emergent TMVr in high-risk patients with ADHF or CS was associated with high short-term mortality and periprocedural complications. Prospective studies are warranted to inform patient selection and periprocedural management for urgent/emergent TMVr.

Outcomes of Emergency Transcatheter Aortic Valve Replacement.

OBJECTIVE: To identify outcomes of patients undergoing emergency transcatheter aortic valve replacement (TAVR) and determine predictors of in-hospital mortality. BACKGROUND: Emergency TAVR has emerged as a viable treatment strategy for patients with decompensated severe aortic stenosis and/or regurgitation; however, data on patients undergoing emergency TAVR are limited. METHODS: All emergency TAVR procedures were identified from a single tertiary academic center between January 2015 and August 2018. RESULTS: 31 patients underwent emergency TAVR due to cardiogenic shock (26 patients), electrical instability with incessant ventricular tachycardia (2 patients), severe refractory angina (2 patients), and decompensated heart failure with hypoxemic respiratory failure requiring mechanical ventilation (1 patient). Mechanical circulatory support (MCS) was used in 16 (51.6%). MCS initiation occurred immediately prior to TAVR in 10 patients and placed post-TAVR in 6 patients. 6 patients died before hospital discharge (in-hospital mortality 19.4%). 1-year and 2-year survival rates were 61.0% and 55.9%, respectively. Univariate predictors of in-hospital mortality were preprocedural pulmonary artery pulsatility index (PAPi) ≤1.8 (66.7% vs. 20.0%, p=0.01), intraprocedural cardiopulmonary resuscitation (CPR) (83.3% vs 4.0%, p ≤ 0.001), acute kidney injury post-TAVR (80.0% vs. 4.2%, p ≤ 0.001), initiation of dialysis post-TAVR (60.0% vs. 4.2%, p ≤ 0.001), and MCS initiation post-TAVR (50.0% vs. 12.0%, p=0.03). MCS initiation before TAVR was associated with improved survival compared with post-TAVR initiation. CONCLUSION: Emergency TAVR in extreme risk patients with acute decompensated heart failure or cardiogenic shock secondary to severe aortic valve disease is associated with high in-hospital mortality rates. Careful patient selection taking into account right heart function, assessed by PAPi, and early utilization of MCS may improve survival following emergency TAVR.

Correction: Comparative prognostic accuracy of sepsis scores for hospital mortality in adults with suspected infection in non-ICU and ICU at an academic public hospital.

[This corrects the article DOI: 10.1371/journal.pone.0222563.].

Comparative prognostic accuracy of sepsis scores for hospital mortality in adults with suspected infection in non-ICU and ICU at an academic public hospital.

BACKGROUND: Sepsis is a global healthcare challenge and reliable tools are needed to identify patients and stratify their risk. Here we compare the prognostic accuracy of the sepsis-related organ failure assessment (SOFA), quick SOFA (qSOFA), systemic inflammatory response syndrome (SIRS), and national early warning system (NEWS) scores for hospital mortality and other outcomes amongst patients with suspected infection at an academic public hospital. MEASUREMENTS AND MAIN RESULTS: 10,981 adult patients with suspected infection hospitalized at a U.S. academic public hospital between 2011-2017 were retrospectively identified. Primary exposures were the maximum SIRS, qSOFA, SOFA, and NEWS scores upon inclusion. Comparative prognostic accuracy for the primary outcome of hospital mortality was assessed using the area under the receiver operating characteristic curve (AUROC). Secondary outcomes included mortality in ICU versus non-ICU settings, ICU transfer, ICU length of stay (LOS) >3 days, and hospital LOS >7 days. Adjusted analyses were performed using a model of baseline risk for hospital mortality. 774 patients (7.1%) died in hospital. Discrimination for hospital mortality was highest for SOFA (AUROC 0.90 [95% CI, 0.89-0.91]), followed by NEWS (AUROC 0.85 [95% CI, 0.84-0.86]), qSOFA (AUROC 0.84 [95% CI, 0.83-0.85]), and SIRS (AUROC 0.79 [95% CI, 0.78-0.81]; p<0.001 for all comparisons). NEWS (AUROC 0.94 [95% CI, 0.93-0.95]) outperformed other scores in predicting ICU transfer (qSOFA AUROC 0.89 [95% CI, 0.87-0.91]; SOFA AUROC, 0.84 [95% CI, 0.82-0.87]; SIRS AUROC 0.81 [95% CI, 0.79-0.83]; p<0.001 for all comparisons). NEWS (AUROC 0.86 [95% CI, 0.85-0.86]) was also superior to other scores in predicting ICU LOS >3 days (SOFA AUROC 0.84 [95% CI, 0.83-0.85; qSOFA AUROC, 0.83 [95% CI, 0.83-0.84]; SIRS AUROC, 0.75 [95% CI, 0.74-0.76]; p<0.002 for all comparisons). CONCLUSIONS: Multivariate prediction scores, such as SOFA and NEWS, had greater prognostic accuracy than qSOFA or SIRS for hospital mortality, ICU transfer, and ICU length of stay. Complex sepsis scores may offer enhanced prognostic performance as compared to simple sepsis scores in inpatient hospital settings where more complex scores can be readily calculated.

Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel.

Gene-targeted deletion of the potassium channel Kv1.3 (Kv1.3(-∕-)) results in "Super-smeller" mice with a sensory phenotype that includes an increased olfactory ability linked to changes in olfactory circuitry, increased abundance of olfactory cilia, and increased expression of odorant receptors and the G-protein, Golf. Kv1.3(-∕-) mice also have a metabolic phenotype including lower body weight and decreased adiposity, increased total energy expenditure (TEE), increased locomotor activity, and resistance to both diet- and genetic-induced obesity. We explored two cellular aspects to elucidate the mechanism by which loss of Kv1.3 channel in the olfactory bulb (OB) may enhance glucose utilization and metabolic rate. First, using in situ hybridization we find that Kv1.3 and the insulin-dependent glucose transporter type 4 (GLUT4) are co-localized to the mitral cell layer of the OB. Disruption of Kv1.3 conduction via construction of a pore mutation (W386F Kv1.3) was sufficient to independently translocate GLUT4 to the plasma membrane in HEK 293 cells. Because olfactory sensory perception and the maintenance of action potential (AP) firing frequency by mitral cells of the OB is highly energy demanding and Kv1.3 is also expressed in mitochondria, we next explored the structure of this organelle in mitral cells. We challenged wildtype (WT) and Kv1.3(-∕-) male mice with a moderately high-fat diet (MHF, 31.8 % kcal fat) for 4 months and then examined OB ultrastructure using transmission electron microscopy. In WT mice, mitochondria were significantly enlarged following diet-induced obesity (DIO) and there were fewer mitochondria, likely due to mitophagy. Interestingly, mitochondria were significantly smaller in Kv1.3(-∕-) mice compared with that of WT mice. Similar to their metabolic resistance to DIO, the Kv1.3(-∕-) mice had unchanged mitochondria in terms of cross sectional area and abundance following a challenge with modified diet. We are very interested to understand how targeted disruption of the Kv1.3 channel in the OB can modify TEE. Our study demonstrates that Kv1.3 regulates mitochondrial structure and alters glucose utilization; two important metabolic changes that could drive whole system changes in metabolism initiated at the OB.