Clinical Characteristics and Outcomes of Patients With Primary Plasma Cell Leukemia in the Era of Novel Agent Therapy

ObjectiveTo evaluate the clinical outcomes of patients with primary plasma cell leukemia (pPCL) defined by 5% or greater clonal circulating plasma cells on peripheral blood smear and treated with novel agent induction therapies.Patients and MethodsA cohort of 68 patients with pPCL diagnosed at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, to December 31, 2019, and treated with novel agent induction therapies was evaluated.ResultsThe median follow-up was 46 (95% CI, 41 to 90) months. The median bone marrow plasma cell content was 85% (range, 10% to 100%) and median clonal circulaitng plasma cell percentage on the peripheral blood smear was 26% (range, 5% to 93%). There was a preponderance of t(11;14) primary cytogenetic abnormality in this cohort. The median time to next therapy (TTNT) and overall survival (OS) for all patients with pPCL patients in this cohort was 13 (95% CI, 9 to 17) and 23 (95% CI, 19 to 38) months, respectively. However, when stratified by cytogenetic risk, the median TTNT and OS were 16 and 51 months for standard risk vs 9 and 19 months for high risk (P=.01 for OS).ConclusionPrimary plasma cell leukemia remains an aggressive disease with poor prognosis despite novel agent–based therapies. Some patients have better than expected survival and this phenomenon may be influenced by the absence of high-risk cytogenetics. Newer treatment regimens are needed to improve the prognosis of this devastating disease.     

Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap

ObjectiveTo examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR).Patients and MethodsWe retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed.ResultsAt baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m² was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11).ConclusionIn contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m² or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap.     

Survival in 222 Patients With Severe CSCI: An 8-Year Epidemiologic Survey in Western China

ObjectiveTo assess the survival and the predictors of mortality in patients with severe cervical spinal cord injuries (CSCI).DesignRetrospective study.ParticipantsFrom January 1, 2010, to May 31, 2018, patients who suffered from severe CSCIs in Western China were enrolled in this study (N=222).InterventionsNot applicable.Main Outcome MeasuresSurvival rates and mortality risk factors. Measures were calculated by the product-limit method (Kaplan-Meier) and the Cox model.ResultsThe overall 1-year, 3-year, 5-year, and 8-year postoperative mortalities were 24.4%, 30.6%, 33.3%, 36.2%, and 39.0%, respectively. Most deaths occurred within 36 months after the injury. According to the Cox proportional hazards model, the significant predictors of survival were as follows: (1) age; (2) neurologic level; (3) treatment options (surgical or conservative); (4) ventilator support (P<.05). The 8-year mortality for older patients (>50y) was 50.2%, which was significantly higher than that for younger patients (32.4%, <50y). The risk of death was 2.053 times higher in higher levels of injury (C1-C4) than in lower levels of injury (C5-C8) (P<.05). Compared with conservative treatment, patients who received surgical treatment (either anterior or posterior decompression) had a lower risk of death (P<.05). No significant difference was detected in the risk of death between early surgery (<3d) and mid-term surgery (3-7d) (P>.05). However, patients who received late-term surgery (>7d) had a higher mortality risk (P<.05). The overall 8-year mortality risk of patients who needed ventilator support was much higher than those who did not need ventilator support (P<.05).ConclusionsAge, neurologic level, ventilator dependence, treatment options, and timing to surgery were main risk factors for mortality in patients with severe CSCIs. Better understanding of the predictors for survival could possibly contribute to the improvement of survival rates.     

A Population-Based Study of the Incidence and Natural History of Degenerative Thoracic Aortic Aneurysms

ObjectiveTo investigate the incidence and natural history of degenerative thoracic aortic aneurysms (TAAs) and compare results between ascending (aTAAs) and descending TAAs (dTAAs).Patients and MethodsThis population-based cohort study used the Rochester Epidemiology Project database from January 1, 1995, through December 31, 2015. Patients were classified as the aTAA or dTAA group.ResultsOf 238 Olmsted County residents studied, 131 (55.0%) were women; 154 (64.7%) were in the aTAA group, and 84 (35.3%) were in the dTAA group. Median age was 77.0 years (interquartile range, 69.1-83.8 years). The overall age- and sex-adjusted incidence rate was 13.8 per 100,000 person-years (95% CI, 12.1 to 15.6) and varied from 9.9 in 1995 to 1999 to 19.0 in 2005 to 2009. It was 9.0 (95% CI, 7.5 to 10.4) for the aTAA and 4.9 (95% CI, 3.8 to 5.9) for the dTAA group. Overall 5-year survival was 62.5%, lower than the expected survival of 73.7% for the US 2010 census population (P<.001). The 5-year survival was 42.9% for the aTAA and 73.4% for the dTAA group (P<.001). On multivariable analysis, advanced age and smoking status were associated with all-cause mortality. The 5-year estimate of freedom from an aortic-related event was 80.0%, lower for dTAAs (67.8%) than for aTAAs (85.2%; P<.001). Maximal aortic diameter and dTAAs were associated with aortic-related events.ConclusionThe incidence of TAAs was stable from 1995 to 2015 and mortality for those with TAAs remains higher than for the general population. Older age and smoking status were associated with overall mortality, whereas larger aneurysms and dTAAs were associated with aortic-related events.     

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization

ObjectiveTo assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.MethodsFrom January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.ResultsIn multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).ConclusionRCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.     

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.     

Coronary Artery Bypass Grafting in Octogenarians—Risks,Outcomes, and Trends in 1283 Consecutive Patients

ObjectiveTo describe the risks, outcomes, and trends in patients older than 80 years undergoing coronary artery bypass grafting (CABG).MethodsWe retrospectively studied 1283 consecutive patients who were older than 80 years and underwent primary isolated CABG from January 1, 1993, to October 31, 2019, in our clinic. Kaplan-Meier survival probability and quartile estimates were used to analyze patients’ survival. Logistic regression models were used for analyzing temporal trends in CABG cases and outcomes. A multivariable Cox proportional hazards regression model was developed to study risk factors for mortality.ResultsOperative mortality was overall 4% (n=51) but showed a significant decrease during the study period (P=.015). Median follow-up was 16.7 (interquartile range, 10.3-21.1) years, and Kaplan-Meier estimated survival rates at 1 year, 5 years, 10 years, and 15 years were 90.2%, 67.9%, 31.1%, and 8.2%, respectively. Median survival time was 7.6 years compared with 6.0 years for age- and sex-matched octogenarians in the general US population (P<.001). Multivariable Cox regression analysis identified older age (P<.001), recent atrial fibrillation or flutter (P<.001), diabetes mellitus (P<.001), smoking history (P=.006), cerebrovascular disease (P=.04), immunosuppressive status (P=.01), extreme levels of creatinine (P<.001), chronic lung disease (P=.02), peripheral vascular disease (P=.02), decreased ejection fraction (P=.03) and increased Society of Thoracic Surgeons predicted risk score (P=.01) as significant risk factors of mortality.ConclusionAlthough CABG in octogenarians carries a higher surgical risk, it may be associated with favorable outcomes and increase in long-term survival. Further studies are warranted to define subgroups benefiting more from surgical revascularization.     

The Role of Biological Effective Dose in Predicting Obliteration After Stereotactic Radiosurgery of Cerebral Arteriovenous Malformations

ObjectiveTo determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs).Patients and MethodsWe studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity–[1–specificity]).ResultsThis study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001).ConclusionBiological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning.     

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.     

High-Intensity Interval Training in Cardiac Rehabilitation: Impact on Fat Mass in Patients With Myocardial Infarction

ObjectiveTo examine the effect of high-intensity interval training (HIIT) on body fat mass and distribution in patients with myocardial infarction (MI) who underwent cardiac rehabilitation (CR).Patients and MethodsWe retrospectively screened 391 consecutive patients with MI enrolled in CR between September 1, 2015, and February 28, 2018. We included 120 patients who completed 36 CR sessions and underwent pretest-posttest dual-energy x-ray absorptiometry; 90 engaged in HIIT, and 30 engaged in moderate-intensity continuous training (MICT). High-intensity interval training included 4 to 8 alternating intervals of high- (30-60 seconds at a rating of perceived exertion [RPE] of 15-17 [Borg scale range, 6-20]) and low-intensity (1-5 minutes at RPE <14), and MICT performed for 20 to 45 minutes of exercise at an RPE of 12 to 14. Body weight, fat mass, and lean mass were measured via dual-energy x-ray absorptiometry with lipid profile measured via clinical procedures.ResultsThe HIIT and MICT groups were similar in age (67 vs 67 years), sex (26.7% [24 of 90 patients in the HIIT group] vs 26.7% [8 of 30 in the MICT group), and body mass index (30.3 vs 29.5 kg/m²) at baseline. The HIIT group had greater reductions in body fat percentage (P<.001), fat mass (P<.001), abdominal fat percentage (P<.001), waist circumference (P=.01), total cholesterol (P=.002), low-density lipoprotein cholesterol (P<.001), and triglycerides (P=.006). Improvements in total body mass and body mass index were not different across groups. After matching exercise duration, exercise intensity, and energy expenditure, HIIT-induced improvements in total fat mass (P=.02), body fat percentage (P=.01), and abdominal fat percentage (P=.02) persisted.ConclusionOur data suggest that supervised HIIT results in significant reductions in total fat mass (P<.001) and abdominal fat percentage (P<.001) and improved lipid profile in patients with MI who undergo CR.     

Obesity is a Major Risk Factor for Hospitalization in Community-Managed COVID-19 Pneumonia

ObjectiveWe aimed to investigate whether the stratification of outpatients with coronavirus disease 2019 (COVID-19) pneumonia by body mass index (BMI) can help predict hospitalization and other severe outcomes.Patients and MethodsWe prospectively collected consecutive cases of community-managed COVID-19 pneumonia from March 1 to April 20, 2020, in the province of Bergamo and evaluated the association of overweight (25 kg/m² ≤ BMI <30 kg/m²) and obesity (≥30 kg/m²) with time to hospitalization (primary end point), low-flow domiciliary oxygen need, noninvasive mechanical ventilation, intubation, and death due to COVID-19 (secondary end points) in this cohort. We analyzed the primary end point using multivariable Cox models.ResultsOf 338 patients included, 133 (39.4%) were overweight and 77 (22.8%) were obese. Age at diagnosis was younger in obese patients compared with those overweight or with normal weight (P<.001), whereas diabetes, dyslipidemia, and heart diseases were differently distributed among BMI categories. Azithromycin, hydroxychloroquine, and prednisolone use were similar between BMI categories (P>.05). Overall, 105 (31.1%) patients were hospitalized, and time to hospitalization was significantly shorter for obese vs over- or normal-weight patients (P<.001). In the final multivariable analysis, obese patients were more likely to require hospitalization than nonobese patients (hazard ratio, 5.83; 95% CI, 3.91 to 8.71). Results were similar in multiple sensitivity analyses. Low-flow domiciliary oxygen need, hospitalization with noninvasive mechanical ventilation, intubation, and death were significantly associated with obesity (P<.001).ConclusionIn patients with community-managed COVID-19 pneumonia, obesity is associated with a higher hospitalization risk and overall worse outcomes than for nonobese patients.     

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.     

Effects of additive corticosteroid therapy on 90-day survival in patients with community-onset pneumonia

IntroductionSystemic corticosteroid therapy is occasionally used as an additive therapy, especially for patients with severe pneumonia. However, its recommendation for use in patients with pneumonia varies worldwide, and its efficacy is unclear.MethodsAdult Japanese patients hospitalized with community-onset pneumonia between January and December 2012 were analyzed using the Diagnostic Procedure Combination database. The patients were classified into mild-to-moderate and severe groups using the A-DROP (age, dehydration, respiration, orientation, and blood pressure) system. The 90-day survival rate was evaluated between the presence or absence of corticosteroid treatment using the Kaplan-Meier method in the overall, mild-to-moderate and severe groups, respectively. The patients’ clinical characteristics were adjusted between the two groups using the inverse probability of treatment weighting method.ResultsAmong 123,811, 110,534 patients were classified as mild-to-moderate grade (corticosteroid group: 8,465, non-corticosteroid group: 102,069) and 13,277 patients were classified as severe grade (corticosteroid group: 1,338, non-corticosteroid group: 11,939). The 90-day survival rate was higher in the non-corticosteroid group than in the corticosteroid group in patients with pneumonia of overall grade (weighted hazard ratio [HR]: 1.36; P < 0.001) and those with mild-to-moderate grade (weighted HR: 1.46; P < 0.001). However, there were no significant differences in the outcomes between the two groups in those with severe grade (weighted HR: 1.08; P = 0.38).ConclusionsAdditive systemic corticosteroid therapy may be related to poor 90-day prognosis in patients with mild-to-moderate grade community-onset pneumonia, although it may not be positively associated with its prognosis in those with severe grade.     

Fitness and Mortality Among Persons 70 Years and Older Across the Spectrum of Cardiovascular Disease Risk Factor Burden: The FIT Project

ObjectiveTo determine whether fitness could improve mortality risk stratification among older adults compared with cardiovascular disease (CVD) risk factors.MethodsWe examined 6509 patients 70 years of age and older without CVD from the Henry Ford ExercIse Testing Project (FIT Project) cohort. Patients performed a physician-referred treadmill stress test between 1991 and 2009. Traditional categorical CVD risk factors (hypertension, hyperlipidemia, diabetes, and smoking) were summed from 0 to 3 or more. Fitness was grouped as low, moderate, and high (<6, 6 to 9.9, and ≥10 metabolic equivalents of task). All-cause mortality was ascertained through US Social Security Death Master files. We calculated age-adjusted mortality rates, multivariable adjusted Cox proportional hazards, and Kaplan-Meier survival models.ResultsPatients had a mean age of 75±4 years, and 3385 (52%) were women; during a mean follow-up of 9.4 years, there were 2526 deaths. A higher fitness level (P<.001), not lower CVD risk factor burden (P=.31), was associated with longer survival. The age-adjusted mortality rate per 1000 person-years was 56.7 for patients with low fitness and 0 risk factors compared with 24.9 for high fitness and 3 or more risk factors. Among patients with 3 or more risk factors, the adjusted mortality hazard was 0.68 (95% CI, 0.61 to 0.76) for moderate and 0.51 (95% CI, 0.44 to 0.60) for high fitness compared with the least fit.ConclusionAmong persons aged 70 years and older, there was no significant difference in survival of patients with 0 vs 3 or more risk factors, but a higher fitness level identified older persons with good long-term survival regardless of CVD risk factor burden.     

Implementation of an All-Day Artificial Intelligence–Based Triage System to Accelerate Door-to-Balloon Times

ObjectiveTo implement an all-day artificial intelligence (AI)–based system to facilitate chest pain triage in the emergency department.MethodsThe AI-based triage system encompasses an AI model combining a convolutional neural network and long short-term memory to detect ST-elevation myocardial infarction (STEMI) on electrocardiography (ECG) and a clinical risk score (ASAP) to prioritize patients for ECG examination. The AI model was developed on 2907 twelve-lead ECGs: 882 STEMI and 2025 non-STEMI ECGs.ResultsBetween November 1, 2019, and October 31, 2020, we enrolled 154 consecutive patients with STEMI: 68 during the AI-based triage period and 86 during the conventional triage period. The mean ± SD door-to-balloon (D2B) time was significantly shortened from 64.5±35.3 minutes to 53.2±12.7 minutes (P=.007), with 98.5% vs 87.2% (P=.009) of D2B times being less than 90 minutes in the AI group vs the conventional group. Among patients with an ASAP score of 3 or higher, the median door-to-ECG time decreased from 30 minutes (interquartile range [IQR], 7?59 minutes) to 6 minutes (IQR, 4?30 minutes) (P<.001). The overall performances of the AI model in identifying STEMI from 21,035 ECGs assessed by accuracy, precision, recall, area under the receiver operating characteristic curve, F1 score, and specificity were 0.997, 0.802, 0.977, 0.999, 0.881, and 0.998, respectively.ConclusionImplementation of an all-day AI-based triage system significantly reduced the D2B time, with a corresponding increase in the percentage of D2B times less than 90 minutes in the emergency department. This system may help minimize preventable delays in D2B times for patients with STEMI undergoing primary percutaneous coronary intervention.     

Outcomes and Echocardiographic Follow-up After Surgical Management of Tricuspid Regurgitation in Patients With Transvenous Right Ventricular Leads

ObjectiveTo evaluate outcomes of elective surgical management of tricuspid regurgitation (TR) in patients with transvenous right ventricular leads, and compare results between non–lead-induced and lead-induced TR patients.Patients and MethodsWe studied patients with right ventricular leads who underwent tricuspid valve surgery from January 1, 1993, through December 31, 2015, and categorized them as non–lead-induced and lead-induced TR. Propensity score (PS) for the tendency to have lead-induced TR was estimated from logistic regression and was used to adjust for group differences.ResultsFrom the initial cohort of 470 patients, 444 were included in PS-adjustment analyses (174 non–lead-induced TRs [123 repairs, 51 replacements], 270 lead-induced TRs [129 repairs, 141 replacements]). In PS-adjusted multivariable analysis, lead-induced TR was not associated with mortality (P=.73), but tricuspid valve replacement was (hazard ratio, 1.59; 95% CI, 1.13 to 2.25; P=.008). Five-year freedom from tricuspid valve re-intervention was 100% for non–lead-induced TR and 92.3% for lead-induced TR; rates adjusted for PS differed between groups (P=.005). There was significant improvement in TR postoperatively in each group (P<.001). In patients having tricuspid valve repair, TR grades tended to worsen over time, but the difference in trends was not significantly different between groups.ConclusionLead-induced TR did not affect long-term survival after elective tricuspid valve surgery. In patients with lead-induced TR, tricuspid valve re-intervention was more common. Improvement in TR was achieved in both groups after surgery; however, severity of TR tended to increase over follow-up after tricuspid valve repair.     

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.     

Sequence of Splenectomy and Rituximab for the Treatment of Steroid-Refractory Immune Thrombocytopenia: Does It Matter?

ObjectiveTo evaluate the impact of the sequence of treatment with rituximab and/or splenectomy on time to relapse for patients with steroid-refractory immune thrombocytopenia (ITP).Patients and MethodsPatients 18 years or older with steroid-refractory immune thrombocytopenia who underwent treatment with splenectomy or rituximab from January 1, 2002, through December 31, 2015, at Mayo Clinic. Evaluation included freedom from relapse (FFR) and response rates after treatment with rituximab or splenectomy as single or sequential interventions.ResultsA total of 218 eligible patients with ITP who were treated according to standard of care were included in this analysis. Patients failing steroids treated with splenectomy had a higher 5-year FFR than did those treated with rituximab (67.4% vs 19.2%; P<.001, propensity-score matched). Patients who failed splenectomy and were then treated with rituximab had a 2-year FFR similar to that of patients who failed rituximab and were then treated with splenectomy (73.4% vs 59.9%; P=.52). Patients treated with rituximab after splenectomy had a longer 2-year FFR than did patients treated with rituximab as a second-line treatment (73.4% vs 29.0%; P<.001).ConclusionFor patients with ITP that relapse after treatment with steroids, splenectomy provides longer FFR than rituximab as a second-line therapy. Among patients who fail second-line treatment with splenectomy or rituximab, those who end up receiving sequential splenectomy-rituximab or rituximab-splenectomy therapy seem to derive similar benefit in the long term. Patients who received rituximab after splenectomy seem to derive superior benefit than do those who are treated with rituximab with an intact spleen.     

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.     

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19–Positive Compared With COVID-19–Negative Patients

ObjectiveTo determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)–positive compared with COVID-19–negative patients.Patients and MethodsAdult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list.ResultsWe identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive–patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death.ConclusionEarly experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.