Comparison of in-hospital outcomes of ST-elevation myocardial infarction patients with cardiogenic shock receiving left ventricular mechanical circulatory support devices based on transfer status.

BACKGROUND: We aimed to compare outcomes in patients who receive on-site left ventricular mechanical support versus those transferred to other facilities for mechanical support in ST-elevation myocardial infarction (STEMI) patients with cardiogenic shock. METHODS: This retrospective study analyzed data from the 2016 to 2020 Nationwide Inpatient Sample (NIS) database. We identified patients with STEMI and cardiogenic shock who received Impella and LVAD placement during their hospital stay. They were divided into two groups: those with in-house (direct) placement and those transferred to higher-level medical centers. The primary goal was to compare mortality rates between these groups. RESULTS: During the study, 15,934 (75.2%) received in-house left ventricular support, while 5255 (24.8%) were transferred. Mean age (63 vs. 64 years) and female percentage (25 vs. 26%) were similar. The average time from admission to receiving LV support was 0.8 days for direct group versus 2.8 days for transfer group (p < 0.001). Transferred patients had a higher rate of prior heart failure (68 vs. 79%, p < 0.001) and peripheral vascular disease (10 vs. 14%, p < 0.001) but a lower rate of hypertension (23 vs. 17%, p = 0.003). There were no significant differences in other comorbidities. Primary outcome mortality did not significantly differ (44.9 vs. 44.2, p = 0.66). After multivariate analysis, transferred patients had higher rates of ECMO usage, acute kidney injury, renal replacement therapy, major bleeding, and ischemic stroke. Length of stay (8 vs. 15 days, p < 0.001) and total charges ($391,472 vs. $581,183, p < 0.001) were significantly higher in the transferred group. CONCLUSION: Among STEMI patients with cardiogenic shock, our study found no significant difference in mortality between patients transferred for and those with on-site LV support. Those transferred patients experienced more complications, longer length of stay, and increased hospital costs.

Outcomes in patients with COVID-19 and new onset heart blocks: Insight from the National Inpatient Sample database.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a worldwide health crisis since it first appeared. Numerous studies demonstrated the virus's predilection to cardiomyocytes; however, the effects that COVID-19 has on the cardiac conduction system still need to be fully understood. AIM: To analyze the impact that COVID-19 has on the odds of major cardiovascular complications in patients with new onset heart blocks or bundle branch blocks (BBB). METHODS: The 2020 National Inpatient Sample (NIS) database was used to identify patients admitted for COVID-19 pneumonia with and without high-degree atrioventricular blocks (HDAVB) and right or left BBB utilizing ICD-10 codes. The patients with pre-existing pacemakers, suggestive of a prior diagnosis of HDAVB or BBB, were excluded from the study. The primary outcome was inpatient mortality. Secondary outcomes included total hospital charges (THC), the length of hospital stay (LOS), and other major cardiac outcomes detailed in the Results section. Univariate and multivariate regression analyses were used to adjust for confounders with Stata version 17. RESULTS: A total of 1058815 COVID-19 hospitalizations were identified within the 2020 NIS database, of which 3210 (0.4%) and 17365 (1.6%) patients were newly diagnosed with HDAVB and BBB, respectively. We observed a significantly higher odds of in-hospital mortality, cardiac arrest, cardiogenic shock, sepsis, arrythmias, and acute kidney injury in the COVID-19 and HDAVB group. There was no statistically significant difference in the odds of cerebral infarction or pulmonary embolism. Encounters with COVID-19 pneumonia and newly diagnosed BBB had a higher odds of arrythmias, acute kidney injury, sepsis, need for mechanical ventilation, and cardiogenic shock than those without BBB. However, unlike HDAVB, COVID-19 pneumonia and BBB had no significant impact on mortality compared to patients without BBB. CONCLUSION: In conclusion, there is a significantly higher odds of inpatient mortality, cardiac arrest, cardiogenic shock, sepsis, acute kidney injury, supraventricular tachycardia, ventricular tachycardia, THC, and LOS in patients with COVID-19 pneumonia and HDAVB as compared to patients without HDAVB. Likewise, patients with COVID-19 pneumonia in the BBB group similarly have a higher odds of supraventricular tachycardia, atrial fibrillation, atrial flutter, ventricular tachycardia, acute kidney injury, sepsis, need for mechanical ventilation, and cardiogenic shock as compared to those without BBB. Therefore, it is essential for healthcare providers to be aware of the possible worse predicted outcomes that patients with new-onset HDAVB or BBB may experience following SARS-CoV-2 infection.

In-Depth Analysis of a Case of Persistent Severe Chronic Thromboembolic Pulmonary Hypertension.

Pulmonary hypertension (PH) is a disease characterized by an increase in the pulmonary vascular resistance that typically progresses to right heart failure and death. It is classified into five groups. Management depends on the group classification. Group four PH, chronic thromboembolic pulmonary hypertension (CTEPH) is thought to be a result of acute pulmonary emboli that cause fibrosis and scarring of the pulmonary arteries with consequent obstruction. The diagnosis of CTEPH is made by identifying perfusion abnormalities on ventilation/perfusion (V/Q) scan. Other studies required for the diagnostic evaluation include transthoracic echocardiogram, right heart catheterization, NT pro-B-type natriuretic peptide and thrombophilia evaluation. Several other tests needed to exclude other causes of pulmonary hypertension include high-resolution computed tomography (HRCT), connective tissue disease evaluation, thyroid function testing, human immunodeficiency virus testing, and liver ultrasonography to exclude portal hypertension. The treatment for CTEPH is surgical pulmonary endarterectomy (PEA). In patients who are not candidates or decline PEA, pulmonary balloon angioplasty may be useful, however, further studies are required. Several pulmonary artery hypertension medications have been studied in the management of inoperable CTEPH or persistent PH following PEA including bosentan (improves hemodynamics but not exercise capacity), macitentan (improves both hemodynamics and clinical parameters), and riociguat (improves both hemodynamics and exercise capacity). However, only riociguat is approved by the Food and Drug Administration for this indication.

Impact of Human Immunodeficiency Virus Infection on Takotsubo Cardiomyopathy Outcomes in a Large Nationwide Sample.

BACKGROUND/PURPOSE: Takotsubo cardiomyopathy (TCM) or stress-induced cardiomyopathy is characterized by transient wall-motion abnormalities often preceded by physical or emotional stress. Various baseline medical comorbidities were associated with worse outcomes, theoretically due to their effect on chronic stress exposure. The effect of concurrent human immunodeficiency virus (HIV) infection on outcomes of TCM has not been well-established. METHODS/MATERIAL: We conducted a US-wide analysis of TCM hospitalizations from 2006 to 2014 by querying the National Inpatient Sample database for the International Classification of Diseases, Ninth Revision TCM code, baseline characteristics, and inpatient outcomes. TCM patients with HIV were compared to TCM patients without HIV. Multivariate regression models were constructed to account for potential confounders. RESULTS: We identified 123,050 patients hospitalized with TCM; of those patients, 304 had positive HIV status. In an unadjusted analysis, in-hospital outcomes were worse in TCM patients with HIV infection in terms of development of acute kidney injury (16.8% vs 33.3%, P-value 0.002), use of invasive mechanical ventilation (18.3% vs 34.5%, P-value 0.003), and mortality (5.3% vs 17.1%, P-value <0.0001). After adjusting for age, gender, and comorbidities, there was no significant difference in the captured outcomes. CONCLUSION: TCM patients with concurrent HIV had numerically worse outcomes. After adjusting for potential confounders, the statistical significance no longer existed, suggesting that statistical difference was primarily driven by difference in baseline sociodemographic parameters and coexisting comorbidities.

Pulse-Chase Proteomics of the App Knockin Mouse Models of Alzheimer's Disease Reveals that Synaptic Dysfunction Originates in Presynaptic Terminals.

Compromised protein homeostasis underlies accumulation of plaques and tangles in Alzheimer's disease (AD). To observe protein turnover at early stages of amyloid beta (Aß) proteotoxicity, we performed pulse-chase proteomics on mouse brains in three genetic models of AD that knock in alleles of amyloid precursor protein (APP) prior to the accumulation of plaques and during disease progression. At initial stages of Aß accumulation, the turnover of proteins associated with presynaptic terminals is selectively impaired. Presynaptic proteins with impaired turnover, particularly synaptic vesicle (SV)-associated proteins, have elevated levels, misfold in both a plaque-dependent and -independent manner, and interact with APP and Aß. Concurrent with elevated levels of SV-associated proteins, we found an enlargement of the SV pool as well as enhancement of presynaptic potentiation. Together, our findings reveal that the presynaptic terminal is particularly vulnerable and represents a critical site for manifestation of initial AD etiology. A record of this paper's transparent peer review process is included in the Supplemental Information.

Push and pull of tropomyosin's opposite effects on myosin attachment to actin. A chimeric tropomyosin host-guest study.

Tropomyosin is a ubiquitous actin-binding protein with an extended coiled-coil structure. Tropomyosin-actin interactions are weak and loosely specific, but they potently influence myosin. One such influence is inhibitory and is due to tropomyosin's statistically preferred positions on actin that sterically interfere with actin's strong attachment site for myosin. Contrastingly, tropomyosin's other influence is activating. It increases myosin's overall actin affinity ∼4-fold. Stoichiometric considerations cause this activating effect to equate to an ∼4(7)-fold effect of myosin on the actin affinity of tropomyosin. These positive, mutual, myosin-tropomyosin effects are absent if Saccharomyces cerevisiae tropomyosin replaces mammalian tropomyosin. To investigate these phenomena, chimeric tropomyosins were generated in which 38-residue muscle tropomyosin segments replaced a natural duplication within S. cerevisiae tropomyosin TPM1. Two such chimeric tropomyosins were sufficiently folded coiled coils to allow functional study. The two chimeras differed from TPM1 but in opposite ways. Consistent with steric interference, myosin greatly decreased the actin affinity of chimera 7, which contained muscle tropomyosin residues 228-265. On the other hand, myosin S1 increased by an order of magnitude the actin affinity of chimera 3, which contained muscle tropomyosin residues 74-111. Similarly, myosin S1-ADP binding to actin was strengthened 2-fold by substitution of chimera 3 tropomyosin for wild-type TPM1. Thus, a yeast tropomyosin was induced to mimic the activating behavior of mammalian tropomyosin by inserting a mammalian tropomyosin sequence. The data were not consistent with direct tropomyosin-myosin binding. Rather, they suggest an allosteric mechanism, in which myosin and tropomyosin share an effect on the actin filament.

Rapidly Developing Methicillin-Resistant Staphylococcus Aureus Pericarditis and Pericardial Tamponade.

Methicillin-resistant staphylococcus aureus (MRSA) pericarditis is a rare life-threatening infection. A 46-year-old female with hypertension, acquired immunodeficiency syndrome (AIDS) and recurrent neck abscesses, presented with a neck abscess and sepsis. Bloody purulent drainage from the abscess was found and antibiotics were started. Drainage was positive for MRSA. Four days after, course was complicated by acute pericarditis and pericardial tamponade; pericardial fluid was drained and was positive for MRSA. Vancomycin was continued, and aspirin and colchicine were started. Two days later, there was a recurrent pericardial fluid collection with loculation. Surgery was thought to be dangerous in the setting of CD4 count of 12. She was managed conservatively thereafter, with vancomycin, aspirin and colchicine, and was successfully discharged from the hospital.

Crossing Boundaries: A Rare Case of Cardiac Dysfunction.

Cardiac tumors are relatively rare. Secondary cardiac tumors are by far more common than primary cardiac tumors. Cardiac involvement may occur secondary to hematogenous metastases, direct invasion, or tumor growth into the venous system and extension into the right atrium. Patients can present with a spectrum of conditions, including embolization, obstruction of ventricular outflow tracts, direct invasion of myocardium causing impaired myocardial function, invasion of surrounding tissue, interference with valvular function causing valvular regurgitation, or constitutional non-specific signs and symptoms. Imaging modalities are essential for diagnosis. Management is mostly surgical, but can include other medical strategies as well. We present a case of a 65-year-old male with hepatocellular carcinoma with direct invasion to the heart through the venous system.

Retained Coronary Guidewire Extending to the Right Axillary Artery.

This is a case of a 56-year-old female who presented with inferior ST segment elevation myocardial infarction (STEMI), treated with percutaneous intervention (PCI), which was complicated by a retained guidewire extending from left circumflex artery (at location of obtuse marginal (OM) stent) through the ascending aorta, the right brachiocephalic artery and into the right axillary artery. Patient underwent cardiac CT, with maximum intensity projection image showing the course of the retained guidewire. Percutaneous retrieval was deferred due to risk of damaging the stent, and the patient initially deferred coronary artery bypass (CABG) and surgical retrieval as. She was discharged on triple therapy with Aspirin, Clopidogril and Apixaban for 3 months with no bleeding or thromboembolic complications on a 3-month follow up with cardiology clinic, during which rediscussion of risks and benefits of CABG and surgical retrieval or retained wire took place with the patient. Patient agreed to undergo the procedure and guidewire was retrieved surgically and CABG was done.

Uncommon Anatomic Predisposition to Myocardial Infarction: A Case of Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is a recognized cause of acute coronary syndrome (ACS), and can be associated with life-threatening complications, including thrombus formation with consequent distal coronary artery embolization. Several studies have demonstrated a higher incidence of cardiovascular adverse events and cardiac death in patients with CAE or coronary artery aneurysms compared to those without such abnormalities. Management of symptomatic CAE is similar to coronary artery disease (CAD), where guideline-directed medical therapy is indicated due to coexistence of CAD with acquired CAE. Percutaneous coronary intervention can be attempted; however, it is challenging, as it is associated with lower procedural success, higher rates of stent thrombosis, and repeat revascularization.

Comprehensive assessment of coronary computed tomography angiography by using Leaman and Leiden score in overweight and obese patients.

Coronary computed tomography angiography (CCTA) is a non-invasive modality used to assess for coronary artery disease. The CT Leaman and Leiden scores utilize coronary plaque location, composition and severity of stenosis to risk stratify patients for cardiovascular events with remarkable precision. This study compares the CCTA Leaman and Leiden score between overweight and obese populations in addition to their associated baseline characteristics. All patients who underwent CCTA within the last 1 year from a single institution were included for initial analysis. Body mass index (BMI) was used to classify patients who were overweight (25.0 to < 30 kg/m2) or obese (≥ 30 kg/m2). Patients with a BMI of < 25 kg/m2 were excluded from further analysis. Patients were divided into overweight and obese groups. CT Leaman and Leiden scores, in addition to baseline characteristics were subsequently compared between the two groups. Overall, a strong correlation between CT Leaman and Leiden scores was found (R2 = 0.9831). Patients classified as obese have more coronary lesions 0.71 ± 0.12 vs 0.31 ± 0.50 in overweight patients (p = 0.02) and tended to have a higher positive CT Leiden (5.47 ± 4.10 vs 3.90 ± 1.36, p = 0.2) and Leaman (3.45 ± 2.58 vs 2.35 ± 0.90, p = 0.1). Furthermore, obese patients with a Leiden score > 5 had significantly higher scores compared to overweight patients (10.22 ± 2.54 vs 5.87 ± 0.64, p = 0.016). Obese patients had similar average CT Leaman and Leiden scores compared to overweight individuals but were more likely to have higher CT Leiden scores > 5 which may indicate a higher risk for adverse cardiovascular outcomes.

Long-lived metabolic enzymes in the crystalline lens identified by pulse-labeling of mice and mass spectrometry.

The lenticular fiber cells are comprised of extremely long-lived proteins while still maintaining an active biochemical state. Dysregulation of these activities has been implicated in diseases such as age-related cataracts. However, the lenticular protein dynamics underlying health and disease is unclear. We sought to measure the global protein turnover rates in the eye using nitrogen-15 labeling of mice and mass spectrometry. We measured the 14N/15N-peptide ratios of 248 lens proteins, including Crystallin, Aquaporin, Collagen and enzymes that catalyze glycolysis and oxidation/reduction reactions. Direct comparison of lens cortex versus nucleus revealed little or no 15N-protein contents in most nuclear proteins, while there were a broad range of 14N/15N ratios in cortex proteins. Unexpectedly, like Crystallins, many enzymes with relatively high abundance in nucleus were also exceedingly long-lived. The slow replacement of these enzymes in spite of young age of mice suggests their potential roles in age-related metabolic changes in the lens.

Mini-thin filaments regulated by troponin-tropomyosin.

Striated muscle thin filaments contain hundreds of actin monomers and scores of troponins and tropomyosins. To study the cooperative mechanism of thin filaments, "mini-thin filaments" were generated by isolating particles nearly matching the minimal structural repeat of thin filaments: a double helix of actin subunits with each strand approximately seven actins long and spanned by a troponin-tropomyosin complex. One end of the particles was capped by a gelsolin (segment 1-3)-TnT fusion protein (substituting for normal TnT), and the other end was capped by tropomodulin. EM showed that the particles were 46 +/- 9 nm long, with a knob-like mass attributable to gelsolin at one end. Average actin, tropomyosin, and gelsolin-troponin composition indicated one troponin-tropomyosin attached to each strand of the two-stranded actin filament. The minifilaments thus nearly represent single regulatory units of thin filaments. The myosin S1 MgATPase rate stimulated by the minifilaments was Ca2+-sensitive, indicating that single regulatory length particles are sufficient for regulation. Ca2+ bound cooperatively to cardiac TnC in conventional thin filaments but noncooperatively to cardiac TnC in minifilaments in the absence of myosin. This suggests that thin filament Ca2+-binding cooperativity reflects indirect troponin-troponin interactions along the long axis of conventional filaments, which do not occur in minifilaments. Despite noncooperative Ca2+ binding to minifilaments in the absence of myosin, Ca2+ cooperatively activated the myosin S1-particle ATPase rate. Two-stranded single regulatory units therefore may be sufficient for myosin-mediated Ca2+-binding cooperativity. Functional mini-thin filaments are well suited for biochemical and structural analysis of thin-filament regulation.