Renin Production by Juxtaglomerular Cell Tumors and Clear Cell Renal Cell Carcinoma and the Role of Angiotensin Signaling Inhibitors

ObjectiveTo profile juxtaglomerular cell tumors (JXG) and histologic mimics by analyzing renin expression; to identify non-JXG renin-producing tumors in The Cancer Genome Atlas (TCGA) data sets; and to define the prevalence of hypertension (HTN) and patient outcomes with angiotensin signaling inhibitor (ASI) use in tumors of interest.Patients and MethodsThirteen JXGs and 10 glomus tumors (GTs), a histologic mimic, were evaluated for clinicopathologic features; TCGA data were analyzed to identify non-JXG renin-overexpressing tumors. An institutional registry was queried to determine the incidence of HTN, the use of ASIs in hypertensive patients, and the impact of ASIs on outcomes including progression-free survival (PFS) in a tumor type with high renin expression (clear cell renal cell carcinoma [CC-RCC] diagnosed between January 1, 2005, and December 31, 2012).ResultsWe found an association between renin production and HTN in JXG compared with GT. Analysis of TCGA data found that a subset of CC-RCCs overexpress renin relative to 29 other tumor types. Furthermore, analysis of our institutional registry revealed a high prevalence (64%) of HTN among 1203 patients treated with radical or partial nephrectomy for nonmetastatic CC-RCC. On multivariable Cox regression, patients with HTN treated with ASIs (34%) had improved PFS (hazard ratio, 0.76; 95% CI, 0.57 to 1.00; P=.05) compared with patients with HTN not treated with ASIs (30%).ConclusionThe identification of renin expression in a subset of CC-RCC may provide a biologic rationale for the high prevalence of HTN and improved PFS with ASI use in hypertensive patients with nonmetastatic CC-RCC.     

Continuous Renal Replacement Therapy Liberation and Outcomes of Critically Ill Patients With Acute Kidney Injury

ObjectiveTo examine the association between continuous renal replacement therapy (CRRT) liberation and clinical outcomes among patients with acute kidney injury (AKI) requiring CRRT.MethodsThis single-center, retrospective cohort study included adult patients admitted to intensive care units with AKI and treated with CRRT from January 1, 2007, to May 4, 2018. Based on the survival and renal replacement therapy (RRT) status at 72 hours after the first CRRT liberation, we classified patients into liberated, reinstituted, and those who died. We observed patients for 90 days after CRRT initiation to compare the major adverse kidney events (MAKE₉₀).ResultsOf 1135 patients with AKI, 228 (20%), 437 (39%), and 470 (41%) were assigned to liberated, reinstituted, and nonsurvival groups, respectively. The MAKE₉₀, mortality, and RRT independence rates of the cohort were 62% (707 cases), 59% (674 cases), and 40% (453 cases), respectively. Compared with reinstituted patients, the liberated group had a lower MAKE₉₀ (29% vs 39%; P=.009) and higher RRT independence rate (73% vs 65%; P=.04) on day 90, but without significant difference in 90-day mortality (26% vs 33%; P=.05). After adjustments for confounders, successful CRRT liberation was not associated with lower MAKE₉₀ (odds ratio, 0.71; 95% CI, 0.48 to 1.04; P=.08) but was independently associated with improved kidney recovery at 90-day follow-up (hazard ratio, 1.81; 95% CI, 1.41 to 2.32; P<.001).ConclusionOur study demonstrated a high occurrence of CRRT liberation failure and poor 90-day outcomes in a cohort of AKI patients treated with CRRT.     

Beta-Blocker Exposure and Survival in Patients With Transthyretin Amyloid Cardiomyopathy

ObjectiveTo investigate a potential association between beta-blocker exposure and survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).MethodsIn this real-world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 institutions in Galicia (Spain), survival of 65 patients who received beta blockers on registry enrollment was compared with that of 63 untreated controls by means of both unweighted Cox regression and Cox regression with inverse probability of treatment weighting. Tolerance to and adverse effects of beta blockers were recorded. Median study follow-up was 520 days.ResultsPatients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either unweighted Cox regression (hazard ratio, 0.31; 95% CI, 0.12 to 0.79) or Cox regression with inverse probability of treatment weighting (hazard ratio, 0.18; 95% CI, 0.08 to 0.41; P<.001). Several sensitivity analyses confirmed the internal validity of these results. The overall frequency of beta-blocker suspension due to adverse effects was 25% (95% CI, 15.5% to 34.5%).ConclusionIn this real-world, prospective, multi-institutional registry, patients with ATTR-CM who received beta blockers had lower all-cause mortality than untreated controls.     

Pituitary Adenoma Incidence,Management Trends,and Long-term Outcomes: A 30-Year Population-Based Analysis

ObjectiveTo perform a population-based study of pituitary adenoma epidemiology, including longitudinal trends in disease incidence, treatment patterns, and outcomes.Patients and MethodsIn this study of incident pituitary adenomas in Olmsted County, Minnesota, from January 1, 1989, through December 31, 2019, we identified 785 patients who underwent primary screening, 435 of whom were confirmed as harboring incident pituitary adenomas and were included. Primary outcomes of interest included demographic characteristics, presenting features, and disease outcomes (tumor control, biochemical control, and complications).ResultsAmong our 435 study patients, 438 unique pituitary adenomas were diagnosed at a median patient age of 39 years (interquartile range [IQR], 27 to 58 years). Adenomas were incidentally identified in 164 of the 438 tumors (37%). Common symptomatic presentations included hyperprolactinemia (188 of 438 [43%]) and visual field deficit (47 of 438 [11%]). Laboratory tests confirmed pituitary hormone hypersecretion in 238 of the 435 patients (55%), which was symptomatic in 222. The median tumor diameter was 8 mm (IQR, 5 to 17 mm). Primary management strategies were observation (156 of 438 tumors [36%]), medication (162 of 438 tumors [37%]), and transsphenoidal resection (120 of 438 tumors [27%]). Tumor and biochemical control were achieved in 398 (95%) and 216 (91%) secreting tumors, respectively. New posttreatment pituitary or visual deficits were noted in 43 (11%) and 8 (2%); apoplexy occurred in 28 (6%). Median clinical follow-up was 98 months (IQR, 47 to 189 months). Standardized incidence rates were 3.77 to 16.87 per 100,000 population, demonstrating linear expansion over time (R²=0.67). The mean overall standardized incidence rate was 10.1 per 100,000 population; final point prevalence was 175.1 per 100,000 population.ConclusionPituitary adenoma is a highly incident disease, with prolactin-secreting and incidental lesions representing the majority of tumors. Incidence rates and asymptomatic detection appear to be increasing over time. Presenting symptoms and treatment pathways are variable; however, most patients achieve favorable outcomes with observation or a single treatment modality.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Identification of Functional Limitations and Discharge Destination in Patients With COVID-19

ObjectivesThe objectives of this study were to identify functional limitations in patients with coronavirus 2019 (COVID-19) admitted to acute care hospitals; to evaluate functional limitations by demographic, medical, and encounter characteristics; and to examine functional limitations in relation to discharge destination.Designand Setting:This is a cross-sectional, retrospective study of adult patients with COVID-19 who were discharged from 2 different types of hospitals (academic medical center and a community hospital) within 1 health care system from January 1 to April 30, 2020.ParticipantsPatients were identified from the Cedars-Sinai COVID-19 data registry who had a new-onset positive test for severe acute respiratory syndrome coronavirus 2. A total of 273 patients were identified, which included 230 patients who were discharged alive and 43 patients who died and were excluded from the study sample.InterventionsNot applicable.Main Outcome MeasuresFunctional limitations in patients with COVID-19 in acute care hospitals and the predictors for discharge disposition.ResultsA total of 230 records were analyzed including demographic, encounter, medical, and functional variables. In a propensity score–matched cohort based on age and comorbidity, 88.2% had functional physical health deficits, 72.5% had functional mental health deficits, and 17.6% experienced sensory deficits. In the matched cohort, individuals discharged to an institution experienced greater physical (62.7% vs 25.5%, P<.001) and mental health (49.0% vs 23.5%, P=.006) deficits than patients discharged home. Marital status (odds ratio, 3.17; P=.011) and physical function deficits (odds ratio, 3.63; P=.025) were associated with an increase odds ratio of discharge to an institution.ConclusionsThis research highlights that functional status is a strong predictor for discharge destination to an institution for patients with COVID-19. Patients who were older, in the acute care hospital longer, and with comorbidities were more likely to be discharged to an institution. Rehabilitation is a significant aspect of the health care system for these vulnerable patients. The challenges of adjusting the role of rehabilitation providers and systems during the pandemic needs further exploration. Moreover, additional research is needed to look more closely at the many facets and timing of functional status needs, to shed light in use of interdisciplinary rehabilitation services, and to guide providers and health care systems in facilitating optimal recovery and patient outcomes.     

Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy

ObjectiveTo evaluate the association between proton pump inhibitor (PPI) use and in-hospital gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) taking dual antiplatelet therapy (DAPT).Patients and MethodsThis study is based on the Improving Care for Cardiovascular Disease in China-ACS project, an ongoing collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. A total of 25,567 patients with ACS taking DAPT from 172 hospitals from July 1, 2017, through December 31, 2018, were included. Multivariable Cox regression and propensity score–matched analyses were used to evaluate the association between PPI use and in-hospital GI bleeding.ResultsOf these patients with ACS, 63.9% (n=16,332) were prescribed PPIs within 24 hours of admission. Patients using PPIs had a higher rate of GI bleeding compared with those not using PPIs (1.0% vs 0.5%; P<.001). In the multivariable Cox regression analysis, early PPI use was associated with a 58% higher risk of GI bleeding (hazard ratio, 1.58; 95% CI, 1.15 to 2.18; P=.005). Further propensity score matching attenuated the association but still showed that patients using PPIs had a higher rate of GI bleeding (0.8% vs 0.6%; P=.04).ConclusionIn China, PPIs are widely used within 24 hours of admission in patients with ACS taking DAPT. An increased risk of GI bleeding is observed in inpatients with early PPI use. Randomized trials on early use of PPIs in patients with ACS receiving DAPT are warranted.Trial Registrationclinicaltrials.gov Identifier: NCT02306616.     

Retrospective evaluation of appropriate dosing of cefmetazole for invasive urinary tract infection due to extended-spectrum β-lactamase-producing Escherichia coli

IntroductionThe frequency of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales is steadily increasing worldwide. Therefore, we aimed to evaluate the efficacy and appropriate dosing of cefmetazole (CMZ) in invasive urinary tract infection (iUTI) caused by ESBL-producing Escherichia coli (ESBLEC).MethodsPatients who developed ESBLEC iUTI and received CMZ between January 2007 and December 2018 were identified, and their medical records were reviewed. The time above minimum inhibitory concentration (MIC) (TAM) was calculated using the MIC value obtained from each patient and its simulated CMZ concentration.ResultsThirty-nine patients were included in the study. The median TAM was 92.6% (interquartile range [IQR], 67.6–100). CMZ was clinically efficacious in 38 (97.4%) patients overall and in 11 out of 12 (91.7%) patients with normal renal function who received CMZ at 1 g every 8 h.ConclusionsIn normal renal function, 1 g CMZ infused for over 1 h every 8 h is an efficacious treatment for iUTI caused by ESBLEC with MIC =< 4 mg/L.     

Portopulmonary Hypertension in Nontransplanted Patients: Results of the Largest US Single-Institution Registry

ObjectiveTo explore clinical characteristics, risk profiles, and outcomes of patients with portopulmonary hypertension (PoPH) who have contraindications to liver transplant (LT).MethodsFrom the largest US single-institution registry of patients with PoPH, we analyzed 160 patients who did not receive LT between 1988 to 2019. Pulmonary arterial hypertension (PAH)–pertinent characteristics, hemodynamic features, treatments, and risk stratification were compared at baseline, first follow-up visit, and censor/death time.ResultsMedian survival for the entire cohort was 27.5 months from the diagnosis of PoPH. Overall survival was 89%, 77%, 51%, and 38% at 6 months, 1 year, 3 years, and 5 years, respectively. Survival was significantly affected by the severity of liver disease (P<.001). Most patients received PAH-specific therapies (136 [85%]), predominantly monotherapy (123 [77%)]. With treatment, significant improvements were noted in World Health Organization functional class (P=.04), 6-minute walk distance (P<.001), right ventricular function (P<.001), pulmonary vascular resistance (P<.001), and Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) Lite 2 score (P=.02) univariately. Per European Society of Cardiology risk stratification, no patient met full criteria for low risk at baseline or at follow-up. In a multivariate Cox risk model, 6-minute walk distance, right atrial pressure, pulmonary capillary wedge pressure, bilirubin level, and Model for End-Stage Liver Disease–sodium score of 15 or higher were associated with increased risk of death.ConclusionPatients with PoPH who did not undergo LT had a poor prognosis. This persisted despite use of PAH-specific therapies and significant improvements in hemodynamics, echocardiography parameters of right ventricle function, 6-minute walk distance, and World Health Organization functional class.     

Real-World Experience of Angiotensin Receptor–Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease

ObjectiveTo investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m²), which have been excluded from the landmark trials.Patients and MethodsThis study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m² were further analyzed (the Taiwan Society of Cardiology – Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints.ResultsAfter propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m²) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m² vs 21.4±17.5 mL/min per 1.73 m²; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users.ConclusionOur results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.     

Prediction of Mortality in Coronary Artery Disease: Role of Machine Learning and Maximal Exercise Capacity

ObjectiveTo develop a prediction model for survival of patients with coronary artery disease (CAD) using health conditions beyond cardiovascular risk factors, including maximal exercise capacity, through the application of machine learning (ML) techniques.MethodsAnalysis of data from a retrospective cohort linking clinical, administrative, and vital status databases from 1995 to 2016 was performed. Inclusion criteria were age 18 years or older, diagnosis of CAD, referral to a cardiac rehabilitation program, and available baseline exercise test results. Primary outcome was death from any cause. Feature selection was performed using supervised and unsupervised ML techniques. The final prognostic model used the survival tree (ST) algorithm.ResultsFrom the cohort of 13,362 patients (60±11 years; 2400 [18%] women), 1577 died during a median follow-up of 8 years (interquartile range, 4 to 13 years), with an estimated survival of 67% up to 21 years. Feature selection revealed age and peak metabolic equivalents (METs) as the features with the greatest importance for mortality prediction. Using these 2 features, the ST generated a long-term prediction with a C-index of 0.729 by splitting patients in 8 clusters with different survival probabilities (P<.001). The ST root node was split by peak METs of 6.15 or less or more than 6.15, and each patient’s subgroup was further split by age or other peak METs cut points.ConclusionApplying ML techniques, age and maximal exercise capacity accurately predict mortality in patients with CAD and outperform variables commonly used for decision-making in clinical practice. A novel and simple prognostic model was established, and maximal exercise capacity was further suggested to be one of the most powerful predictors of mortality in CAD.     

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction

ObjectiveTo evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography.MethodsA retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD.ResultsOf 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD?, 86% in MAC?/MVD+, and 92% in MAC?/MVD?. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10).ConclusionIn a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.     

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study

IntroductionThe severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020.MethodsAll patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients’ records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software.ResultsData from 61 patients (16 Pt–CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt–CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt–CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt–CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt–CSI than in Pt-MMI (P = 0.013). Among the 16 Pt–CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died.ConclusionsThe illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.     

Women Are Less Likely to Survive AMI Presenting With Out-of-Hospital Cardiac Arrest: A Nationwide Study

ObjectiveTo assess the impact of patient’s sex on outcomes and management of acute myocardial infarction (AMI) patients presenting with out-of-hospital cardiac arrest (OHCA).Patients and MethodsWe conducted a population-based retrospective cohort study in AMI patients admitted with OHCA between 2010 and 2017 from the Myocardial Ischaemia National Audit Project (MINAP) registry. We used multivariable logistic regression models to evaluate the role of sex as a predictor of clinical outcomes and treatment strategy.ResultsOf 16,278 patients, women constituted almost one-quarter of the population (n=3710 [22.7%]). Women were older (median age 69 [IQR, 57-79] years vs 63 [IQR, 54-72] years, P<.001), experienced longer call-to-hospital-arrival time (median, 1.2 hours vs 1.1 hours; P=.008), were less likely to present with shockable rhythm (86.8% vs 91.5%, P<.001), and less likely to receive dual antiplatelet therapy (73.8% vs 78.6%, P<.001), beta blockers (64.7% vs 72.3%, P<.001), angiotensin-converting enzyme inhibitors (49.0% vs 55.3%, P<.001), coronary angiography (73.7% vs 83.3%, P<.001), and percutaneous coronary intervention (37.5% vs. 40.7%, p 0.004). After adjusting for patient characteristics and management, women had significantly higher odds of in-hospital death compared with men (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.5) and lower odds of receiving coronary angiography (OR, 0.67; 95% CI, 0.59 to 0.75) and coronary artery bypass graft (OR, 0.28; 95% CI, 0.19 to 0.40).ConclusionWomen were less likely to survive following OHCA secondary to AMI. Hospital protocols that minimize physician bias and improve women-physician communication are needed to close this gap.     

Predicting 1-Year Mortality on Admission Using the Mayo Cardiac Intensive Care Unit Admission Risk Score

ObjectiveTo determine whether the Mayo Cardiac Intensive Care Unit (CICU) Admission Risk Score (M-CARS) accurately predicts 1-year mortality.MethodsWe retrospectively reviewed adult CICU patients admitted from January 1, 2007, through April 30, 2018, and calculated M-CARS using admission data. We examined the association between admission M-CARS, as continuous and categorical variables, and 1-year mortality.ResultsThis study included 12,428 unique patients with a mean age of 67.6±15.2 years (4686 [37.7%] female). A total of 2839 patients (22.8%) died within 1 year of admission, including 1149 (9.2%) hospital deaths and 1690 (15.0%) of the 11,279 hospital survivors. The 1-year survival decreased incrementally as a function of increasing M-CARS (P<.001), and all components of M-CARS were significant predictors of 1-year mortality (P<.001). The 1-year survival among hospital survivors decreased incrementally as a function of increasing M-CARS for scores below 3 (all P<.001); however, there was no further decrease in 1-year survival for hospital survivors with M-CARS of 3 or more (P=.99). The M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden skin score, and respiratory failure (all P<.001).ConclusionM-CARS predicted 1-year mortality among CICU admissions, with a plateau effect at high M-CARS of 3 or more for hospital survivors. Significant added predictors of 1-year mortality among hospital survivors included markers of frailty and chronic illness.     

Right Ventricular Enlargement and Dysfunction Are Associated With Increased All-Cause Mortality in Hypertrophic Cardiomyopathy

ObjectiveTo assess whether right ventricular enlargement (RVE) and right ventricular dysfunction (RVD) adversely affect prognosis in hypertrophic cardiomyopathy (HCM).Patients and MethodsData were retrieved from Mayo Clinic’s prospectively collected HCM registry between January 1, 2000, and September 30, 2012. Right ventricle (RV) size and function were semiquantitatively categorized via echocardiography as normal (RV-Norm) versus abnormal (RV-Abn) (RVE or RVD). All-cause mortality was the primary endpoint.ResultsOf 1878 HCM patients studied (mean age 53±15 years; 41.6% female), only 71 (3.8%) had RV-Abn (24 RVE, 28 RVD, 19 combined RVE and RVD). Compared with HCM patients with RV-Norm, RV-Abn patients were older (57±14 vs 53±15 years, P=.02), more symptomatic (New York Heart Association functional class III-IV in 62.0% vs 48.6%, P=.03), had more atrial fibrillation (53.5% vs 17.3%, P<.001), and more prior implantable cardioverter-defibrillator implantation (23.9% vs 11.3%, P=.02). Median follow-up was 9.4 years with 311 deaths. Patients who were RV-Abn had higher all-cause mortality compared with RV-Norm (log-rank P<.001); 24.1% (95% CI, 15.5% to 35.3%) vs 6.1% (95% CI, 5.1% to 7.3%) at 5 years. In multivariable Cox modeling, RV-Abn (hazard ratio, 1.89; 95% CI, 1.18 to 3.03; P=.008) was associated independently with all-cause mortality after adjusting for age, female sex, New York Heart Association functional class, atrial fibrillation, hypertension, coronary artery disease, implantable cardioverter-defibrillator implantation, beta blocker use, prior septal reduction therapy, resting LV outflow tract gradient, maximal LV wall thickness, and moderate or greater tricuspid regurgitation.ConclusionAlthough perturbations in RV size and function were observed in fewer than 5% of patients with HCM, they were associated with nearly two-fold higher all-cause mortality at long-term follow-up.     

Progress Toward Long-Term Survivors of Glioblastoma

ObjectiveTo identify the frequency and characteristics of long-term survivors of glioblastoma.Patients and MethodsUsing all cases of glioblastoma with histopathological confirmation in the National Cancer Database from January 1, 2004, through December 31, 2009, clinical, institutional, and treatment-related factors were evaluated with multivariable logistic regression models so as to elucidate factors independently associated with higher than 5-year overall survival after diagnosis.ResultsA total of 48,652 patients met the inclusion criteria, with 2249 (4.6%) achieving 5-year survival. Factors associated with odds of improved 5-year overall survival in multivariable analysis were younger age, female sex, less medical comorbidities, nonwhite race, highest median income quartile, left-sided tumors and tumors outside the brainstem, and treatment with radiotherapy (P<.05 for all). The percentage of patients surviving 5 years remained relatively unchanged over the 6-year study period (P=.97).ConclusionDespite improvements in median and short-term overall survival shown in recent large clinical trials for glioblastoma, the percentage of patients with glioblastoma achieving 5-year overall survival remains low. This observation calls for the development of practice-redefining therapies and justifies the increased application of radical novel and experimental treatment paradigms for all patients with glioblastoma.     

Classification of Stroke Patients With Dysphagia Into Subgroups Based on Patterns of Submental Muscle Strength and Skill Impairment

ObjectivesTo identify and characterize subgroups of stroke patients with clinical signs of dysphagia, based on swallowing-related strength and skill impairments of the submental muscle group.DesignProspective observational study.SettingInpatient rehabilitation centers and community dwellings.ParticipantsIndividuals (N=114), including stroke patients with dysphagia (n=55) and 2 control groups including myopathic patients with dysphagia (n=19) and healthy volunteers (n=40) were included in this study.InterventionsNot applicable.Main Outcome MeasuresNovel clinical assessment of strength (force generation) and skill (spatial and temporal precision of muscle activation) of the submental muscle group during swallowing and nonswallowing behaviors, using surface electromyography and dynamometry.ResultsHierarchical cluster analysis revealed 4 clusters, which could be broadly characterized as cluster 1: intact strength and skill, cluster 2: poor strength and poor nonswallowing skill, cluster 3: poor strength, and cluster 4: poor strength and poor swallowing skill. Membership in cluster was significantly associated with medical diagnosis (P<.001). The majority of healthy and myopathic participants were assigned to clusters 1 and 3, respectively, whereas stroke patients were found in all 4 clusters. Skill outcome measures were more predictive of cluster assignment than strength measures.ConclusionsAlthough healthy and myopathic participants demonstrated predominantly homogeneous swallowing patterns of submental muscle function within their etiology, several subgroups were identified within stroke, possibly reflecting different subtypes of swallowing function. Future research should focus on the nature and rehabilitation needs of these subtypes. Assessment of skill in swallowing may be an important but overlooked aspect of rehabilitation.     

Examining Disparities and Excess Cardiovascular Mortality Before and During the COVID-19 Pandemic

ObjectiveTo investigate the patterns and demographic features of cardiovascular disease (CVD) death and subtypes myocardial infarction (MI), stroke, and heart failure in the pre–COVID-19 era (2018-2019) vs during the COVID-19 pandemic (2020-2021) in the United States.MethodsIn this cross-sectional study, we used the US Multiple Cause of Death files for 2018 to 2021 to examine the trend of excess cause-specific deaths using International Classification of Diseases, Tenth Revision codes for CVD (I00 to I99), MI (I21 and I22), stroke (I60 to I69), and heart failure (I42 and I50). Our primary outcome was excess mortality from CVD and its 3 subtypes (MI, stroke, and heart failure) between prepandemic (2018-2019) and pandemic (2020-2021) years. We performed a subgroup analysis on race and month-to-month and year-to-year variation using χ² analysis to test statistical significance.ResultsOverall, 3,598,352 CVD deaths were analyzed during the study period. There was a 6.7% excess CVD mortality, 2.5% MI mortality, and 8.5% stroke mortality during the COVID-19 pandemic (2020-2021) compared with the prepandemic era (2018-2019). Black individuals had higher excess CVD mortality (13.8%) than White individuals (5.1%; P<.001). This remained consistent across subtypes of CVD, including MI (9.6% vs 1.0%; P<.001), stroke (14.5% vs 6.9%; P<.001), and heart failure (5.1% vs ?1.2%; P<.001).ConclusionThere has been a significant rise in CVD and subtype-specific mortality during the COVID-19 pandemic that has been persistent despite 2 years since the onset of the pandemic. Excess CVD mortality has disproportionately affected Black compared with White individuals. Further studies targeting and eliminating health care disparities are necessary.     

Prognostic Value of Cardiac Magnetic Resonance Imaging in Acute Coronary Syndrome Patients With Troponin Elevation and Nonobstructive Coronary Arteries

ObjectiveTo define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses.MethodsCardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a “working diagnosis” of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 μg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality.ResultsCardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with “true” MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction.ConclusionsCardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.